With two tablet and film-coated tablet production lines with Japan-GMP standard and customer care policies with the heart, DHG Pharma continues to win the trust of pharmacies, doctors, and consumers
A scientific seminar with the topic “Solutions for screening and preventing stroke” for consumers was organized by DHG Pharma.
Success from a methodical investment
In each step, each stage of development, DHG Pharma always takes the trust, care and companionship of customers as a goal of cohesion and long-term development.
After 47 years of development, DHG Pharma has strived to become the largest generic pharmaceutical enterprise in Vietnam in terms of operational efficiency, distribution system and production capacity. The company has been and continues to build the largest and most extensive distribution system in the country, stretching from urban to rural areas with more than 30,000 customers.
DHG Pharma always considers that customers as “a bridge” to bring the company’s products to consumers, making a significant contribution to the care and health promotion of the community.
Inside the plant where owns production lines with Japan-GMP standard of DHG Pharma.
Accordingly, for public health, for benefit of consumers, DHG Pharma has boldly invested and owned a plant with a maximum capacity of 4 billion product units per year. In addition to modernly invested machinery and equipment, DHG Pharma’s quality human resources are also always concerned. Employees are trained to achieve highly technical and professional qualifications and always has a sense of strict compliance with regulations. All are aimed at providing the market with the best products with guaranteed quality.
“Having worked in the pharmaceutical industry, it is impossible not to know about DHG Pharma. For 20 years, since opening a pharmacy, I have always been assured of consulting and selling the company’s products to users. Especially when the company has 2 production lines with Japan-GMP standard, I am even more confident when choosing DHG Pharma’s products to contribute to everyone’s health. Simply, thanks to DHG Pharma, domestic users have an opportunity to use medicines of international quality at affordable prices”, said Ms. Thuy Nga, owner of Phuong Anh drugstore, Can Tho city shared.
In addition, with a nationwide distribution system, along with more than 100 high-quality products produced on two lines with Japan GMP standard, DHG Pharma has always been recognized by a system of reputable pharmacies, large hospitals, experienced medical professionals and trusted by consumers.
“My family used to choose imported drugs because we thought that foreign medicines meet strict standards, so their quality was also higher than domestic medicines. But since going to the doctor periodically and being advised to use medicines produced on DHG Pharma’s Japan-GMP standard line such as Hapacol 650 in pain relief and fever reducer, anti-allergic agent Telfor, or Fubenzon anthelmintic, I have just found out that a Vietnamese pharmaceutical company has conquered these rigorous standards to provide people with global quality pills – Vietnamese prices. After administering them for a while, I have complete confidence and peace of mind in their quality and do not see much difference with foreign medicine products, even I feel better because I always think Vietnamese medicine is suitable with Vietnamese people”, Mr. A Dong (HCMC) shared.
In the context of late 2020 and early 2021, free trade agreements open up more challenges than opportunities for domestic pharmaceutical companies, but many enterprises still find their own key to open this door.
Over the past decade, Vietnam’s pharmaceutical market has continuously increased due to the impact of economic agreements such as CPTPP, EVFTA, WTO, ATIGA, VJEPA, etc.
Over the years, some enterprises have successfully built up international distribution networks. Prominent is DHG Pharma which brings many its products to Singapore, Moldova, Russia, and Southeast Asia.
Due to the influence of Covid-19, free trade agreements work in the way that is more beneficial to pharmaceutical giants in Vietnamese market. Pharmaceutical exports in Vietnam slowed down due to border closure from epidemic countries. It can be said that 2021, for domestic pharmaceutical companies, will continue to be a year of more challenges than opportunities. The picture of pharmaceutical industry is witnessing a wave of fierce competition in the country between high-quality internal medicines and imported medicines.
In the past 2020, DHG Pharma has had a series of key products such as Hapacol (its main ingredient – Paracetamol), Telfor (its main ingredient – Fexofenadine), AlphaDHG (ingredient Alpha chymotrypsin), Medlon (ingredient Methylprednisolone), Glirit (ingredients Metformin and Glibenclamide), DilodinDHG (ingredients Diosmin and hesperidin), etc. are appreciated and trusted by experts.
FTAs bring challenges for domestic pharmaceutical companies but have created opportunities for Vietnamese people to approach and use good quality products. Japan-GMP is considered a “key” of DHG Pharma when facing challenges as well as seeking opportunities from FTAs.
This enterprise currently holds a team of leading experts on Japan-GMP and international market development and experienced technicians on how-to-operate Japan-GMP line.
The Taisho and DHG story is a “sweet fruit” of the post-M&A pharmaceutical industry, after 5 years of starting to build a solid foundation for DHG Pharma’s international breakthroughs reaching the world.
M&A trend in the pharmaceutical industry has blossomed over the world nearly a decade, however in Vietnam this has only been active a few years ago. A Taisho (Japan) deal Taisho (Japan) increased its ownership in DHG Pharma to 51%.
A handshake of Taisho and DHG Pharma is one of the earliest and most successful “case study” today. Optimizing 5 years of companion, DHG Pharma quickly learns from Japanese partner to become an international drug manufacturing enterprise while Taisho leaders quickly integrate into local culture. Two sides both exchange modern expertise, and respect and reconcile each other to keep unique and traditional traits.
5 years – raising an international level with Japanese partners
Not only mobilizing capital, many pharmaceutical enterprises, when looking for foreign partners for companion, expect to be compensated, supported in management capacity, production technology, professional experience to come into the world. The story of DHG Pharma is typical for this goal, after 3 years of increasing capital, under a support from Taisho, DHG Pharma marks an important transformation with 2 GMP-Japan standard production lines which help to improve quality and increase competitiveness of products by global standards. In the future, the remaining lines will be upgraded to Japan-GMP standard. This is a breakthrough step of DHG Pharma with a mission of raising the level of Vietnamese medicines not only in the domestic market but also firmly reaching the international market.
At two Japan-GMP lines, nearly 300 DHG Pharma technicians currently operate 32 equipment and machines professionally as in Japan. This is a result of DHG Pharma staff being trained in many forms: professional training in Japan, practical training at factories in Vietnam, online exchange between both sides.
In production, two Japan-GMP lines are operating continuously 3 shifts with optimal working speed to reduce product conversion time and optimize the capacity of the lines.
In distribution, DHG Pharma always applies “Just in Time” to optimize production progress, optimize orders, and reduce inventory months. All distribution centers meet GSP standard that helps the quality-ensured circulation of goods. The GLP-achieved laboratory is ready to welcome new drug inventions and innovative technologies.
DHG Pharma always preserves and integrates culture
It is a similarity of Eastern culture that makes two enterprises easy to get acquainted and integrate. DHG Pharma always openly exchanges and absorbs labor beauty from Japan such as Ojigi sincere bowing culture, Shinsho compliance and sincere business culture, rules and ethics linking 4 systems: individuals, companies, customers and society.
Cultural and training programs continues to be inspired and expanded, creating the best working environment for employees and Japanese characteristic culture of retaining personnel “working whole life”. The Board of Management always maintains a close attitude like family members, regularly writes letters of encouragement on Tet holidays, letters of gratitude to members who successfully implemented Japan-GMP.
That agreement is also evident through a continuation of good community activities, supporting people in flood and storm areas, repaying the gratitude for people who have contributed to the revolution, supporting the nation to prevent epidemics, providing free medicine and examination.
After 5 years of cooperation, the result of 2 tablet and film-coated tablet production lines achieving Japan-GMP certification in 2019 and 2020 has created a mark in the pharmaceutical industry, also showing that Taisho’s aspiration in committing to accompany DHG Pharma.
DHG Pharma currently has nearly 100 products manufactured on 2 lines and nearly 100 products reaching Japan-GMP thanks to the durable support from Taisho. DHG Pharma has just announced its business result in 2020 with a profit after tax of VND739 billion, increased by 17% compared to 2019. This is the highest net profit since the company listed on the stock exchange in 2006.
Compared with the plan assigned by shareholders, in the difficult market situation due to the COVID 19 pandemic, DHG Pharma has completed 97% in revenue and exceeding 14% in profit. By the end of 2020, the company keeps its position as the largest pharmaceutical company with its revenue equal to two behind combined competitors and its profitability outstripping the market average.
DHG Pharma said that last year its revenue from self-manufactured products increased and the company focused on selling main products with Japan-GMP standard in cooperation with Taisho.
As from listed in “Top 10 outstanding M&A deals in 2018-2019” voted by Vietnam Investment Review, the story “Taisho – DHG Pharma” has always been interested by consumers. Officially, a strategic cooperation was from 2016, Taisho has committed to enhancing competitive capacity in domestic and foreign markets of DHG Pharma as well as supporting factory improvement to global standard and products with international quality.
Experts at that time said that, this commitment was estimated to take 8 to 10 years to come true, to be able to confirm two enterprises having good companionship and how far they go. However, after only 5 years, a series of achievements have told for all about a sustainable future of both sides. In particular, the biggest achievement is that Taisho has successfully supported DHG Pharma to deploy 2 production lines of tablets and film-coated tablets meeting Japan-GMP standard.
Taking about Japan-GMP, this is the highest drug quality standard from Japan Pharmaceutical and Medical Devices Agency (PMDA). With many and many strict technical barriers, Japan-GMP is prioritized for bidding into high-value drugs in hospital channel in Vietnam, easily applying for visas to Japan, Europe, etc. Therefore, 2 years and 2 Japan-GMP lines can be said to have made a mark in pharmaceutical industry as well as demonstrated Taisho’s commitment in strong companionship to Vietnamese people, helping drug consumers benefit greatly in quality and price.
After 3 years of pursuing Japan-GMP, DHG Pharma has currently owned a list of nearly 100 products meeting Japanese quality standard.
2 production lines and nearly 100 products meeting Japan-GMP
DHG Pharma has currently owned a diversified portfolio of more than 300 products circulating in the market. Now, there are nearly 100 DHG Pharma’s products produced on two Japan-GMP lines of tablet and film-coated tablet.
According to experts, this is a “big” list of products in the current top ranking. The figure of nearly 100 products reflects a large scale of production line as well as leading technology standardization capabilities of pharmaceutical companies. All are completely produced on two Japan-GMP production lines of tablet and fim-coated tablet.
The production line meeting Japan-GMP standard of DHG Pharma.
Japan-GMP is a Good Manufacturing Practice standard standing for Japanese quality directly certified by Japan Pharmaceuticals and Medical Devices Agency (PMDA) – under Japanese Ministry of Health, Labour and Welfare.
After overcoming all strict technical barriers of PMDA, both DHG Pharma’s production lines must continue to undergo a rigorous verification by Department of Drug Administration of Vietnam – Ministry of Health to achieve Japan-GMP certification. Achieving Japan-GMP standard as today results in constant efforts of all employees from production sector and relevant departments through past years.
It is worth mentioning that the product list focuses on antibiotic, analgesic-antipyretic, nervous, hepatobiliary, digestive, cardiovascular, diabetic medicines. These are main lines of DHG Pharma’s pharmaceutical products which own high technology content and meet high needs of end-users.
For example, the antibiotic line has Clabact 250 and 500 (containing active ingredient clarithromycin – treating bacterial infections), Zaromax 250-500 (containing azithromycin). The nervous group has Neni 800 (containing piracetam)
While the digestive and hepatobiliary groups have Raxium, the cardiovascular group including Vastec, respiratory with Telfor 60-120-180 (containing fexofenadine). For the analgesic-antipyretic group, the enterprise upgrades Japan-GMP standard quality for all 16 Hapacol products.
DHG Pharma initially collects sweet fruits with Japan-GMP standard
The year 2020, the pharmaceutical industry saw many “ups – downs” of revenue and profit in the Covid season. In addition to many enterprises achieving their revenues and profit, the industry also recorded many “bottom” companies” due to the impact of pandemic. Among the top companies with effective business for many consecutive years, DHG Pharma continues to make an impression with profit-after-tax 2020 of VND739 billion, increased by 17.0% compared with 2019 and getting the highest growth up to now.
Mrs. Nguyen Ngoc Diep – Deputy General Director in charge of Production and Supply chain of DHG Pharma
DHG Pharma said that positive business results mainly come from its focus on selling strategic and key products, deploying well the projects to increase productivity and production efficacy, having suitable strategies in the pandemic season. The products with Japan-GMP certification initially bring sweet fruits after 3 years of pursuit.
With Japan-GMP standard, the company aims to increase share market in the hospital channel where an opportunity to expand bidding into high standard packages. At the same time, it helps patients to use quality medicines with affordable prices as well as decrease treatment costs and reduce the burden for health insurance fund.
At the same time, the company also prepares procedures for exporting Vietnamese Japan-GMP medicines to the world. Currently, domestic market accounts for 98% DHG Pharma’s revenue; the remainder comes from export activities. With Japan-GMP list of products, DHG Pharma surely openes to bring its medicines to Japan and the world and once again affirming the leading brandname in Vietnam.
However, experts are waiting for DHG Pharma to make a further breakthrough in 2021. Thanks to a large number of Japanese-recognized production lines and a launch pad from Japan-GMP product list. New strategies around Japan-GMP create new values serving users, expected to help DHG Pharma get more and more sweet fruits from Japan-GMP products.
Japan-GMP stands for Japanese quality; assessment steps last 16 to 27 months to verify that the medicine production line has met Japan-GMP.
In the treatment of diseases in the community, medicines are associated with patient’s life. Therefore, groups of medicines that meet international standards such as Japan-GMP, PIC/S-GMP, EU-GMP, CGMP-USA, etc. come from countries with developed medical and pharmaceutical background are put in hospital channel with decentralization and priority. In which, Japan-GMP is one of the quality standards when deciding to prescribe medicines. Tracing the origin and process of creating this certification, the patient will find that medicines that want to achieve Japan-GMP must undergo thorough examinations and tests.
Japan-GMP is a standard of good manufacturing practice pf pharmaceutical products that transcends strict technical barriers to the way of preserving finished products and managing the quality system.
Japan-GMP stands for Japanese quality directly certified by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). This standard of good manufacturing practice sets up technical barriers on raw material standards, aseptic preservation of finished products, quality management system according to ICH Q10 to ensure medicines must be of the highest quality when they reach the patient’s hands.
Therefore, capital investment in Japan-GMP factory lines is estimated to be many times higher than conventional standards. The Japanese PMDA will have to conduct pre-evaluation steps, document review, scientific assessment, factory appraisal, etc. lasting up to 16 to 27 months before announcing the medicine production line with Japan-GMP or not.
From standing for the Japanese highest quality, Japan-GMP is present in many countries around the world, including Vietnam. Japan-GMP is also selected as one of the standards for medicines entering hospital channel, treating mild to severe illnesses.
Inside the medicine production line that meets Japan-GMP standard of DHG Pharma.
DHG Pharma owns two production lines of film-coated tablets and tablets that meet Japan-GMP. On December 18, DHG Pharma announced that it received Japan-GMP certification for the film-coated tablet line and re-certified the previously operated tablet production line.
Mr. Tomoyuki Kawata – Deputy General Director of DHG Pharmaceutical Joint-Stock Company said that this is an achievement after 3 consecutive years of building and maintaining a good production system, investing in hardware (factory, equipment) and software equipment (standard operating documents, production rules). In order to achieve Japan-GMP, for the past 3 years, Taisho experts from Japan provided technical guidance along with relentless efforts of every elite individual at DHG Pharma.
Through more than 30 years of experience in the pharmaceutical industry in Japan, Mr. Kawata found that it is extremely challenging and difficult for foreign companies to obtain JAPAN-GMP certification. Because, Japanese market requires many very strict quality standards related to product’s safety and effectiveness.
Mr. Kawata emphasized that a view on high quality is not only for medicine, but also for many other product lines in Japan. Therefore, in order to be able to maintain stable production of high-quality products, it is not only necessary to implement consistent management from research stage to production stage, but also a thorough production management system from a perspective of data integrity and risk prevention. And above all, each person in that production system needs to be fully equipped with knowledge and training.
Mr. Tomoyuki Kawata – Deputy General Director of DHG Pharmaceutical Joint-Stock Company shared about the company’s journey to achieve Japan-GMP certification.
According to the Deputy General Director of DHG Pharmaceutical Joint Stock Company, Japan-GMP not only certifies product quality and enhances a credibility for DHG Pharma’s products, but also opens an opportunity to use international quality drugs with affordable prices for domestic consumers, Vietnamese medicine products can even be brought to the world. “From now on, we will promote our export to Japan and some ASEAN countries where Taisho Pharmaceutical Group’s subsidiaries are present” Mr. Kawata revealed about DHG Pharma’s medium and long-term vision.
Currently, these two Japan-GMP lines are producing key product groups, contributing about 30% to the company’s revenue. A leader of DHG Pharma said that they are planning to continue to conquer Japan-GMP certification for the effervescent line and some other key lines in the near future.
Link:https://vnexpress.net/tieu-chi-khat-khe-de-thuoc-dat-chuan-japan-gmp-4209461.html
With two JAPAN GMP certified production lines, DHG Pharma will provide international standard medicines to Vietnamese consumers. At the same time, bringing Vietnamese pharmaceutical products to conquer the international market.
On December 18, 2020 in Can Tho, an announcement ceremony of JAPAN GMP certification for DHG Pharma’s medicine production line was held respectfully. Attending the ceremony were leaders of Can Tho City Department of Health, leaders of Mekong Delta hospitals, close customers, DHG Pharma’s leaders and employees.
Ban Tổng Giám đốc DHG cùng thực hiện nghi thức công bố dây chuyền sản xuất thuốc đạt chuẩn JAPAN GMP.
Since 2019, DHG Pharma has been certified JAPAN GMP with tablet production line. In October 2020, DHG Pharma continued to achieve JAPAN GMP certification for film-coated production line. On December 10, 2020, DAV officially announced that DHG Pharma has achieved JAPAN GMP certification for both production lines. In Vietnam, DHG Pharma is the first company to be certified JAPAN GMP. At this time, nationwide there have been only three production lines surpassed high-end technical barriers to achieve JAPAN GMP certification, of which DHG Pharma owns two lines.
For many years to be the leading position in pharmaceutical industry in Vietnam, with JAPAN GMP certification – a standard of good manufacturing practice of pharmaceutical products of Japan that is equivalent to EU GMP of Europe, US-FDA of USA, etc. Firstly, with a distribution network of more than 28,000 pharmacies nationwide, DHG Pharma will provide domestic users with access to internationally qualified pharmaceutical products at affordable prices. After that, DHG Pharma will continue to bring its products to conquer difficult international markets such as Japan, Asian countries, in turn covering other international markets.
Mr. Masashi Nakaura – General Director of DHG Pharmaceutical Joint-Stock Company spoke at the ceremony
Re-certification of JAPAN GMP for the tablet production line and new certification for film-coated production line are a worthy and valuable reward for DHG Pharma’s efforts based on advanced infrastructure potential, highly skilled personnel, investment and support from Taisho Corporation – Japan. With JAPAN GMP certification, DHG Pharma once again affirmed that DHG Pharma has become an international standard pharmaceutical company, continuing to raise the prestige of Can Tho City medical industry to a high altitude; affirming DHG Pharma’s core value “Quality, safety and effectiveness targeted as our highest commitment” to partners, customers and consumers.
DHG Pharma’s Board of Management stated that achievement of JAPAN GMP standard is also a good opportunity for all DHG Pharma’s employees to promote their mutual solidarity and creative efforts for getting higher and further goals, bringing Vietnamese pharmaceutical products to the international level.
Keep out of reach of children.
Read the directions carefully before use.
QUALITATIVE AND QUANTITATIVE COMPOSITION:
Active ingredient: Paracetamol ……………………….. 650 mg
Excipients: Wheat starch, pregelatinized starch, magnesium stearate, sodium starch glycolate, talc, aerosil, strawberry-flavored powder, PVP K30, sodium benzoate.
PHARMACEUTICAL FORM: Tablet.
Product description: A white to off-white, fragrant caplet, a break-line on one side, a diamond-shaped on the other, intact edges.
THERAPEUTIC INDICATIONS: Treatment of painful symptoms in cases of headache, migraine, toothache, aches and pains caused by flu, sore throat, musculoskeletal pains, arthritis-induced pains, pains after vaccination or tooth extraction.
Antipyretic actions on patients with cold or diseases associated with fever.
POSOLOGY AND METHOD OF ADMINISTRATION: Hapacol 650 should be orally given every 4 hours and not more than 6 tablets per day.
Adults and children aged > 12 years: 1 tablet each time.
Do not take the drug by self-administration for relief of fever for more than 3 days or for relief of pain for more than 10 days.
Or as prescribed by the physician.
Notes:
* Maximum dose/24 hours: not more than 4 g and given every 4 hours.
* Prolonged self-administration should not be advised, consult a physician if:
– New symptoms occur.
– Fever gets high (39.50C) and lasts more than 3 days or recurs.
– Pain gets worse or lasts more than 5 days.
CONTRAINDICATIONS: Hypersensitivity to any components of the drug. Patients with glucose – 6 – phosphate dehydrogenase deficiency.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Individuals with phenylketonuria and other individuals who must restrict their intake of phenylalanine should avoid co-administration of paracetamol and aspartame-containing medicines or food.
Patients with hypersensitivity (asthma) should not use concurrently paracetamol and sulfite-containing medicines or food.
Cautions should be taken in patients with previous anemia, liver and kidney failure.
Because chronic, excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity, it is advised to avoid chronic ingestion of alcohol.
The physician should warn patients of serious signs of skin reactions such as Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Lyell’s syndrome, acute generalized exanthematous pustulosis (AGEP).
USE IN PREGNANCY AND LACTATION:
Safety of paracetamol on foetus has not determined when administered to pregnant women. Therefore, the drug should be only used in pregnant women if clearly needed.
Studies in breast-feeding mothers showed that use of paracetamol causes no adverse effect in breast-fed infants
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The drug does not affect the possibility of driving and operating machinery.
INTERACTIONS:
Chronic ingestion of large doses of paracetamol has been reported to potentiate the effects of coumarin- and indandione-derivative anticoagulants.
The possibility of severe hypothermia should be considered in patients receiving concomitant phenothiazine and antipyretic therapy.
Anticonvulsants (including phenytoin, barbiturates, carbamazepine), isoniazid and antituberculosis drugs may increase paracetamol-induced liver toxicity.
Chronic, excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity.
UNDESIRABLE EFFECTS:
Uncommonly: rash; nausea, vomiting; rephropathy, renal toxicity due to long-term abuse; neutropenia, pancytopenia, anemia.
Rarely: hypersensitive reactions
Please inform your doctor of all undesirable effects upon drug administration.
OVERDOSE: Paracetamol toxicity may result from a single toxic dose, from repeated ingestion of large doses of paracetamol (e.g. 7.5 – 10 g daily for 1 – 2 days), or from chronic ingestion of the drug. Dose-dependent, hepatic necrosis is the most serious acute toxic effect associated with overdosage and potentially fatal.
Symptoms of paracetamol overdosage include nausea, vomiting, abdominal pain, cyanosis on skin, mucosa, and nails.
In severe poisoning, mild stimulation, excitement, and delirium may occur initially. This may be followed by CNS depression; stupor; hypothermia; marked prostration; rapid, shallow breathing; rapid, weak, irregular pulses; low blood pressure; and circulatory failure.
Treatment: Early diagnosis is very important in treatment of paracetamol overdosage.
In the event of severe paracetamol intoxication, full supportive measures should also be instituted. Gastric lavage should be carried out especially if the overdose was taken within the previous 4 hours.
The main detoxication therapy is use of sulfhydryl compound. N-acetylcysteine gives its effect followed by oral route or an intravenous infusion.
Methionine, activated charcoal and/or salt cathartics are also advised to treat overdose.
PHARMACODYNAMIC PROPERTIES:
ATC code: N02B E01
Paracetamol produces effective analgesia, antipyresis. The drug acts on the hypothalamic heat-regulating center to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. Paracetamol lowers body temperature in patients with fever but rarely lowers normal body temperature. Paracetamol produces analgesia by elevation of the pain threshold.
With therapeutic doses, the analgesic, antipyretic effects of paracetamol are similar to those of aspirin. Paracetamol appears to have little effect on cardiovascular and respiratory system, causes no acid – base balance, no gastric irritation, scratch, bleeding.
PHARMACOKINETIC PROPERTIES: Paracetamol is rapidly and completely absorbed by the gastrointestinal tract. The elimination half-life of paracetamol varies from about 1.25 to 3 hours. Paracetamol is metabolized predominantly by the liver and excreted by the kidney.
PRESENTATION: Box of 10 blisters x 5 tablets. Box of 10 blisters x 10 tablets. Box of 25 blisters x 10 tablets. Bottle of 100 tablets. Bottle of 200 tablets.
SHELF-LIFE: 36 months from the manufacturing date.
STORAGE CONDITIONS: Store in dry places, not exceeding 30oC, protect from light.
SPECIFICATIONS: Manufacturer’s.
COMPOSITION:
Paracetamol …………………………… 650 mg
Caffeine ………………………………….. 65 mg
Excipients q.s …………………………. 1 tablet
(Pregelatinized starch, avicel, wheat starch, sodium starch glycolate, erythrosine lake, talc, magnesium stearate, PVP K30, aerosil, nipagin).
DOSAGE FORM: Tablet.
PRESENTATIONS: Box of 10 blisters x 10 tablets.
ACTIONS: Hapacol 650 Extra is combination of paracetamol and caffeine.
Paracetamol produces effective analgesia, antipyresis. The drug acts on the hypothalamic heat-regulating center to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. Paracetamol lowers body temperature in patients with fever but rarely lowers normal body temperature. With therapeutic doses, the analgesic, antipyretic effects of paracetamol are similar to those of aspirin. Paracetamol appears to have little effect on cardiovascular and respiratory system, causes no acid – base balance, no gastric irritation, scratch, bleeding. Paracetamol has no effect on inflammatory treatment. Paracetamol is rapidly and completely absorbed by the gastrointestinal tract. The elimination half-life of paracetamol varies from about 1.25 to 3 hours. Paracetamol is metabolized predominantly by the liver and excreted by the kidneys.
Caffeine stimulates all levels of the CNS. Caffeine is well absorbed by the gastrointestinal tract and obtained plasma maximum concentration in adults after 1 hour. The plasma half-life is about 3 to 7 hours. Caffeine is metabolized predominantly by the liver and excreted in urine.
INDICATIONS:
Relief of painful attacks including headache, migraine, sore throat, dysmenorrhea, tooth extraction or dental surgeries, toothache, myalgia, tenodynia, traumatic injuries, arthritis- and sinusitis-associated pains, pains due to cold or flu.
CONTRAINDICATIONS:
Hypersensitivity to any ingredients of the drug. Patients with glucose-6-phosphate dehydrogenase deficiency.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Individuals with phenylketonuria and other individuals who must restrict their intake of phenylalanine should be advised no concurrent administration of paracetamol and aspartame-containing drugs or food.
In patients with hypersensitivity (asthma), concomitant administration of paracetamol and sulfite-containing foods or drugs should not be recommended. Caution should be exercised in patients with previous anemia, hepatic and renal impairment. Because excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity; it is advised to avoid chronic ingestion of alcohol.
High doses of caffeine may cause hypertension; the drug should be used cautiously in patients with hypertension.
For paracetamol-containing agents: The physician should warn patients of serious signs of skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Lyell’s syndrome, acute generalized exanthematous pustulosis (AGEP).
PREGNANCY AND LACTATION:
The drug is only used in pregnant and nursing women if really necessary.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The drug does not affect the possibility of driving and using machines.
INTERACTIONS:
Chronic ingestion of large doses of paracetamol has been reported to potentiate the effects of coumarin- and indandione-derivative anticoagulants. The possibility of severe hypothermia should be considered in patients receiving concomitant phenothiazine and antipyretic therapy. Anticonvulsants (including phenytoin, barbiturates, carbamazepine), isoniazid may increase paracetamol-induced liver toxicity. Excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity. Concurent administration of the drug with caffeine-containing drinks including tea, coffee, and some canned drinks is not recommended. Half-life of caffeine has been increased by concurrently using with antibiotics including ciprofloxacin, enoxacin, lomefloxacin, norfloxacin, ofloxacin. No concurrent use of caffeine with phenytoin, fluvoxamine, terbinafine, cimetidin, methoxsalen, contraceptives, phenylpropanolamine, ephedrin, theophylline is recommended.
ADVERSE EFFECTS:
Paracetamol rarely causes adverse effects. It sometimes causes allergy, rash, nausea, vomiting; pancytopenia, hypoleukemia, anemia. Chronic ingestion of large doses of paracetamol may lead to hepatic impairment (due to hepatolysis).
High doses of caffeine may cause hypertension, daytime sleepiness. Besides, other side effects include nausea, vomiting, diarrhea, insomnia, headache, tremble, palpitations, anxiety.
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE:
Paraceramol overdosage: Paracetamol toxicity may result from a single toxic dose, from repeated ingestion of large doses of paracetamol (e.g. 7.5 – 10 g daily for 1 – 2 days), or from chronic ingestion of the drug. Dose-dependent, hepatic necrosis is the most serious acute toxic effect associated with overdosage and potentially fatal.
Symptoms of paracetamol overdose include nausea, vomiting, colic, cyanosis on skin, mucosa, nails.
Treatment: In the event of severe paracetamol overdose, full supportive measures should also be instituted. Gastric lavage should be carried out especially if the overdose was taken within the previous 4 hours.
The main detoxication therapy is use of sulfhydryl compound. N-acetylcysteine gives its effect followed by oral route or an intravenous infusion. N-acetylcysteine should be administered as soon as possible, preferably within 36 hours of overdosage. N-acetylcysteine is more effective if administered within 10 hours of overdosage.
Methionin, activated charcoal and/or salt cleaners are also used to treat overdose.
Caffeine overdosage has been rarely reported. They can be drowsiness, palpitation, agitation, and delirum.
DOSAGE & ADMINISTRATION:
Adults and children aged > 12 years: The recommended dose is 1 tablet, 3 to 4 times daily. The interval between oral doses should be at least 4 to 6 hours. Do not exceed 6 tablets daily.
For patients with severe renal impairment (creatinine clearance < 10 ml per minute), the interval between oral doses should be at least 8 hrs.
Or as prescribed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
Shelf-life: 36 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer’s.
COMPOSITION:
Paracetamol……………………………. 500 mg
Caffeine ………………………………….. 65 mg
Excipients q.s…………………………. 1 caplet
(Pregelatinized starch, avicel, wheat starch, sodium starch glycolate, erythrosine lake color, talc, magnesium stearate, strawberry-flavored powder, PVP K30, sodium benzoate).
DOSAGE FORM: Caplets.
PRESENTATION: Box of 10 blisters x 10 caplets.
ACTIONS: Hapacol Extra is a combination of paracetamol and caffeine:
Paracetamol produces effective analgesia, antipyresis. The drug acts on the hypothalamic heat-regulating to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. Paracetamol lowers body temperature in patients with fever but rarely lowers normal body temperature. With therapeutic doses, the analgesic, antipyretic effects of paracetamol are similar to those of aspirin. Paracetamol appears to have little effect on cardiovascular and respiratory system, causes no acid – base balance, no gastric irritation, scratch, bleeding. Paracetamol is rapidly and completely absorbed by the gastrointestinal tract. The elimination half-life of paracetamol varies from about 1.25 to 3 hours. Paracetamol is metabolized predominantly by the liver and excreted by the kidney.
Caffeine stimulates all levels of the CNS. It helps to relieve pains and supports muscular activities to be acted easily. Caffeine is well absorbed by the gastrointestinal tract and obtained plasma maximum concentration in adults after 1 hour. The plasma half-life is about 3 to 7 hours. Caffeine is metabolized by the liver and excreted by the urine.
INDICATIONS: Relief of painful attacks including headache, migraine, sore throat, dysmenorrhea, pains after tooth extraction or dental surgeries, toothache, myalgia, tenodynia, traumatic injuries, arthritis- and sinusitis-associated pains, pains and aches due to cold, flu.
CONTRAINDICATIONS: Hypersensitivity to any component of the drug. Patients with glucose-6-phosphate dehydrogenase deficiency.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Individuals with phenylketonuria and other individuals who must restrict their intake of phenylalanine should be warned that no concurrent administration of paracetamol and aspartame-containing food or drugs.
Patients with hypersensitivity (asthma) should not use concurrently paracetamol and sulfite-containing food or drugs.
The drug should be used with caution in patients with previous anemia, hepatic and renal failure.
Because chronic, excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity, it is advised to avoid chronic ingestion of alcohol.
High doses of caffeine may cause hypertension; use with caution in patients with hypertension.
For the paracetamol-containing drugs, the physician should warn patients of serious signs of skin reactions such as Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Lyell’s syndrome, acute generalized exanthematous pustulosis (AGEP).
PREGNANCY AND LACTATION:
The drug only gives pregnant and nursing women if really necessary.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The drug does not affect the possibility of driving and operating machines.
INTERACTIONS:
Chronic ingestion of large doses of paracetamol has been reported to potentiate the effects of coumarin- and indandione-derivative anticoagulants.
The possibility of severe hypothermia should be considered in patients receiving concomitant phenothiazine and antipyretic therapy.
Anticonvulsants (including phenytoin, barbiturates, carbamazepine), isoniazid and other antituberculosis drugs may increase paracetamol-induced liver toxicity.
Chronic, excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity.
Avoid concurrent administration of the drug with caffeine-containing drinks including tea, coffee, and some canned drinks. Half-life of caffeine has been increased by concurrent administration with antibiotics including ciprofloxacin, enoxacin, lomefloxacin, norfloxacin, ofloxacin. No concurrent use of caffeine and phenytoin, fluvoxamine, terbinafine, cimetidin, methoxsalen, contraceptives, phenylpropanolamine, ephedrin, theophylline is recommended.
ADVERSE EFFECTS: Paracetamol rarely causes adverse effects. However, symptoms of allergy, rash, nausea, vomiting have been sometimes reported. In some cases, pancytopenia, hypoleukemia, anemia may occur. Prolonged use and high doses of paracetamol may lead to hepatic impairment (due to hepatolysis).
In concerning with caffeine: High doses of caffeine may cause hypertension, daytime somnolence. Besides, other side effects include nausea, vomiting, diarrhea, insomnia, headache, tremble, palpitations, anxiety have been reported.
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE: Paracetamol overdosage: Paracetamol toxicity may result from a single toxic dose, from repeated ingestion of large doses of paracetamol (e.g. 7.5 – 10 g daily for 1 – 2 days), or from chronic ingestion of the drug. Dose-dependent, hepatic necrosis is the most serious acute toxic effect associated with overdosage and potentially fatal. Symptoms of paracetamol overdosage include nausea, vomiting, colic, cyanosis on skin, mucosa, and nails.
Treatment of overdosage:
In the event of severe paracetamol overdose, full supportive measures should also be instituted. Gastric lavage should be carried out especially if the overdose was taken within the previous 4 hours.
The main detoxication therapy is use of sulfhydryl compound. N-acetylcysteine gives its effect followed by oral route or an intravenous infusion. N-acetylcysteine should be administered as soon as possible, preferably within 36 hours of overdosage. N-acetylcysteine is more effective if administered within 10 hours of overdosage.
Methionin, activated charcoal and/or salt cathartics are also advised to treat overdose.
Caffeine overdosage has been rarely reported. They can be drowsiness, palpitation, agitation, and delirum.
DOSAGE & ADMINISTRATION: Adults and children aged > 12 years are orally given 1 to 2 caplets, 1 to 4 times daily.
Do not exceed 8 caplets daily.
The interval between oral doses should be at least 4 hours.
Or as prescribed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
Shelf-life: 36 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer’s.
COMPOSITION:
Acetaminophen ………………………. 500 mg
Excipients q.s …………………………. 1 tablet
(Wheat starch, avicel, aerosil, magnesium stearate, sodium starch glycolate, PVP K30, sodium benzoate, green).
DOSAGE FORM: Tablet.
PRESENTATIONS:
Box of 10 blisters x 10 tablets.
Bottle of 200 tablets.
ACTIONS:
Acetaminophen produces analgesia, antipyresis. The drug acts on the hypothalamic heat-regulating center to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. Acetaminophen lowers body temperature in patients with fever but rarely lowers normal body temperature.
With therapeutic doses, the analgesic and antipyretic effects of acetaminophen are similar to those of aspirin. Acetaminophen appears to have little effect on cardiovascular and respiratory system, causes no acid – base balance, no gastric irritation, scratch, bleeding.
Acetaminophen is rapidly and almost completely absorbed by the gastrointestinal tract. The elimination half-life of acetaminophen varies from about 1.25 to 3 hours. Acetaminophen is metabolized predominantly by the liver and excreted by the kidney.
INDICATIONS:
Treatment of painful symptoms in cases of headache, migraine, toothache, aches and pains caused by flu, sore throat, musculoskeletal pains, arthritis-induced pains, pains after vaccination or tooth extraction.
Antipyretic actions on patients with cold or diseases associated with fever.
CONTRAINDICATIONS:
Hypersensitivity to any component of the drug. Patients with glucose-6-phosphate dehydrogenase deficiency.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Individuals with phenylketonuria and other individuals who must restrict their intake of phenylalanine should be warned that concurrent use of acetaminophen and aspartame-containing food or drug should not be recommended.
Patients with hypersensitivity (asthma) should not use concurrently acetaminophen and sulfite-containing food or drugs.
Cautions should be taken in patients with previous anemia, hepatic and renal impairments.
Because chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, it is advised to avoid chronic ingestion of alcohol.
The physician should warn patients of serious signs of skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Lyell’s syndrome, acute generalized exanthematous pustulosis (AGEP).
PREGNANCY AND LACTATION:
Safety of acetaminophen on foetus has not determined when administered to pregnant women. Therefore, the drug should be used in pregnant women if clearly needed.
Studies in breast-feeding mothers showed that acetaminophen cause no adverse effects at nursing infants
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The drug does not affect the possibility of driving vehicles and operating machinery.
INTERACTIONS:
Chronic ingestion of large doses of acetaminophen has been reported to potentiate the effects of coumarin- and indandione-derivative anticoagulants.
The possibility of severe hypothermia should be considered in patients receiving concomitant phenothiazine and antipyretic therapy.
Anticonvulsants (including phenytoin, barbiturates, carbamazepine), isoniazid and other antituberculosis drugs may increase acetaminophen-induced liver toxicity.
Acetaminophen may cause liver damage if you consume more alcoholic drinks for a long time.
ADVERSE EFFECTS:
Uncommonly: rash; nausea, vomiting; rephropathy, renal toxicity due to chronic ingestion; neutropenia, pancytopenia, anemia.
Rarely: hypersensitive reactions
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE:
Acetaminophen toxicity may result from a single toxic dose, from repeated ingestion of large doses of acetaminophen (e.g. 7.5 – 10 g daily for 1 – 2 days), or from chronic ingestion of the drug. Dose-dependent, hepatic necrosis is the most serious acute toxic effect associated with overdosage and potentially fatal.
Symptoms of acetaminophen overdosage include nausea, vomiting, abdominal pain, cyanosis on skin, mucosa, and nails.
In severe poisoning, mild stimulation, excitement, and delirium may occur initially. This may be followed by CNS depression; stupor; hypothermia; marked prostration; rapid, shallow breathing; rapid, weak, irregular pulses; low blood pressure; and circulatory failure.
Treatment: Early diagnosis is very important in treatment of acetaminophen overdosage.
In the event of severe acetaminophen intoxication, full supportive measures should also be instituted. Gastric lavage should be carried out especially if the overdose was taken within the previous 4 hours.
The main detoxication therapy is use of sulfhydryl compound. N-acetylcysteine gives its effect followed by oral route or an intravenous infusion.
Methionin, activated charcoal and/or saline cathartic are also advised to treat overdose.
DOSAGE & ADMINISTRATION:
Adults and children aged > 12 years: oral dose of 1 tablet each time.
Adults may take 2 tablets each time in severe cases.
The drug should be given every 4 hours and not more than 8 tablets daily.
Or as prescribed by the physician.
Notes:
* Maximum dose / 24 hours: not more than 4g and given every 4 hours.
* Prolonged self-administration should not be advised. Ask your physician if:
– new symptoms occur.
– fever gets worse (39.50C) and lasts for more than 3 days or recurs
– pain gets worse or lasts for more than 5 days.
Read the directions carefully before use.
Consult the physician for more information.
Shelf-life: 24 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 300C, protect from light
Specifications: Manufacturer’s.
COMPOSITION:
Paracetamol ……………………….. 500 mg
Excipients.q.s……………………….. 1 tablet
(Wheat starch, avicel, aerosil, magnesium stearate, sodium starch glycolate, PVP K30, sodium benzoate, HPMC, PEG 6000, titanium dioxide, talc).
DOSAGE FORM: Film coated tablet.
PRESENTATION: Box of 10 blisters x 10 tablets.
ACTIONS: Paracetamol produces effective analgesia, antipyresis. The drug acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. Paracetamol lowers body temperature in patients with fever but rarely lowers normal body temperature. With therapeutic doses, the analgesic, antipyretic effects of paracetamol are similar to those of aspirin. Paracetamol appears to have little effect on cardiovascular and respiratory system, causes no acid – base balance, no gastric irritation, scratch, bleeding.
Paracetamol is rapidly and almost completely absorbed by the gastrointestinal tract. The elimination half-life of paracetamol varies from about 1.25 to 3 hours. Paracetamol is metabolized predominantly by the liver and excreted by the kidney.
INDICATIONS: – Treatment of painful symptoms in cases of headache, migraine, toothache, aches and pains caused by flu, sore throat, musculoskeletal pains, arthritis-induced pains, pains after vaccination or tooth extraction.
– Antipyretic actions on patients with cold or fever-associated diseases.
CONTRAINDICATIONS: Hypersensitivity to any component of the drug. Patients with glucose-6-phosphate dehydrogenase deficiency.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Individuals with phenylketonuria and other individuals who must restrict their intake of phenylalanine should be advised no concurrent administration of paracetamol and aspartame-containing food or drugs.
Patients with hypersensitivity (asthma) should not use concurrently paracetamol and sulfite-containing food or drugs.
Cautions should be taken in patients with previous anemia, hepatic and renal impairments.
Because chronic, excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity, it is advised to avoid chronic ingestion of alcohol.
The physician should warn patients of serious signs of skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or Lyell’s syndrome, acute generalized exanthematous pustulosis (AGEP).
PREGNANCY AND LACTATION:
Safety of paracetamol on foetus has not determined when administered to pregnant women. Therefore, the drug should be only used in pregnant women if clearly needed. Studies in breast-feeding mothers showed that paracetamol causes no adverse effect at breast-fed infants
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The drug does not affect the possibility of driving vehicles and operating machinery.
INTERACTIONS: Chronic ingestion of large doses of paracetamol has been reported to potentiate the effects of coumarin- and indandione-derivative anticoagulants. The possibility of severe hypothermia should be considered in patients receiving concomitant phenothiazine and antipyretic therapy.
Anticonvulsants (including phenytoin, barbiturates, carbamazepine) isoniazid and other antituberculosis drugs may increase paracetamol-induced liver toxicity. Paracetamol may cause liver damage if you consume more alcoholic drinks for a long time.
ADVERSE EFFECTS: Uncommonly: rash; nausea, vomiting; rephropathy, renal toxicity when long-term abuse; neutropenia, pancytopenia, anemia.
Rarely: hypersensitive reactions.
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE: Paracetamol toxicity may result from a single toxic dose, from repeated ingestion of large doses of paracetamol (e.g. 7.5 – 10 g daily for 1 – 2 days), or from chronic ingestion of the drug. Dose-dependent, hepatic necrosis is the most serious acute toxic effect associated with overdosage and potentially fatal.
Symptoms of paracetamol overdosage include nausea, vomiting, abdominal pain, cyanosis on skin, mucosa, and nails.
In severe poisoning, mild stimulation, excitement, and delirium may occur initially. This may be followed by CNS depression; stupor; hypothermia; marked prostration; rapid, shallow breathing; rapid, weak, irregular pulses; low blood pressure; and circulatory failure.
Treatment: Early diagnosis is very important in treatment of paracetamol overdosage. In the event of severe paracetamol intoxication, full supportive measures should also be instituted. Gastric lavage should be carried out especially if the overdose was taken within the previous 4 hours. The main detoxication therapy is use of sulfhydryl compound. N-acetylcysteine gives its effect followed by oral route or an intravenous infusion. Methionine, activated charcoal and/or saline cathartic are also advised to treat overdose.
DOSAGE & ADMINISTRATION:
Adults and children aged > 12 years: oral dose of 1 tablet each time. Adults may be given 2 tablets each time in severe cases.
Hapacol Blue should be orally given every 4 hours and not more than 8 tablets daily. Or as prescribed by the physician.
Notes:
* Maximum dose/24 hours: not more than 4 g, given every 4 hours.
* Prolonged self-administration is not recommended. Ask a doctor if:
– new symptoms occur.
– fever gets high (39.50C) and lasts more than 3 days or recurs.
– pain gets worse or lasts more than 5 days.
Read the directions carefully before use
Consult the physician for more information
Shelf-life: 36 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light
Specifications: Manufacturer’s.
COMPOSITION:
Fexofenadine HCl ………………………………………………. 180 mg
Excipients q.s …………………………………………………… 1 tablet
(Pregelatinized starch, microcrystalline cellulose M101, croscarmellose sodium, magnesium stearate, HPMC 606, HPMC 615, PEG 6000, titanium dioxide, talc, red ferric oxide, orange E110).
DOSAGE FORM: Film coated tablet
PRESENTATION: Box of 2 blisters x 10 tablets.
PHARMACODYNAMICS:
Telfor contains the active ingredient Fexofenadine which is a selectively peripheral H1-receptor histamine antagonist and is used to treat the allergy. At the therapeutic dose, fexofenadine causes no drowsiness or other CNS effects. Fexofenadine gives a quick and prolonged action because it slowly binds to H1-receptor, forming a stable complex and slow division.
PHARMACOKINETICS:
Fexofenadine is rapidly absorbed following oral administration. The plasma peak concentrations occur at 2 – 3 hours post-dose. Food reduces the plasma peak concentration by 17%. Fexofenadine is 60 to 70% bound to plasma proteins, primarily albumin and alpha1-acid glycoprotein. The mean elimination half-life of fexofenadine was 14.4 hours. Approximately 11% of an oral dose of fexofenadine is excreted in the urine, primarily as unchanged drug and 80% is excreted in faeces.
INDICATIONS:
Symptomatic treatment of unknown chronic urticaria in adults and children over 12 years old.
CONTRAINDICATIONS:
Hypersensitivity to any components of the drug.
PRECAUTIONS:
Patients with a history of or ongoing cardiovascular disease or previous prolonged QT interval should be warned. Avoid concurrently administrating fexofenadine with other antihistamine agents.
Caution and dose adjustment should be exercised in kidney failure patients and the elderly (over 65 years) who suffered from decreased renal function. Fexofenadine should be discontinued at least 24 to 48 hrs prior to intradermally injected antigen tests. The safety of fexofenadine 180 mg in children under 12 years of age has not been established.
PREGNANCY AND LACTATION:
There are no adequate data from the use of fexofenadine in pregnant women. Therefore, fexofenadine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Data for content in human milk after administration of fexofenadine is not available; therefore, caution should be taken in breast-feeding mothers.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
Although fexofenadine rarely causes drowsiness, caution should be exercised in drivers and machine users.
INTERACTIONS:
Co-administration of fexofenadine with either ketoconazole or erythromycin led to increased plasma concentrations of fexofenadine because of increased absorption and decreased elimination of fexofenadine. However, the interaction has no meaning of clinical significance.
Antacids containing aluminium and magnesium hydroxide gels cause a reduction in the bioavailability of fexofenadine, most likely due to binding in the gastrointestinal tract. Therefore, it is advisable to leave 2 hours between administration of fexofenadine and aluminium and magnesium hydroxide containing antacids.
Grapefruit juice reduces the absorption and exposure of fexofenadine.
ADVERSE EFFECTS:
Common: CNS disorders: drowsiness, fatigue, headache, insomnia, dizziness. Gastrointestinal disorders: nausea, indigestion. Others: viral infections (cold, influenza), dysmenorrhea, upper respiratory infections, itchy throat, cough, fever, otitis media, sinusitis, back pain.
Uncommon: CNS disorders: fear, sleep disturbances, nightmares. Gastrointestinal disorders: dry mouth, abdominal pain.
Rare: Skin disorders: rash, pruritus. Hypersensitivity reactions: angioedema, chest discomfort, dyspnea, flushing, anaphylactic shock.
Inform a physician about any adverse effects occur during the treatment.
OVERDOSAGE:
Reports on acute toxicity of fexofenadine are limited; however, dizziness, drowsiness, and dry mouth have been reported.
Treatment: Standard measures should be considered to remove any unabsorbed medicinal product. Symptomatic and supportive treatment is recommended. Hemodialysis did not effectively remove fexofenadine, from blood (up to 1.7% removed). There is no specific antidote.
DOSAGE & ADMINISTRATION:
Adults and children aged more than 12 years: oral dose of 1 tablet daily.
Or as directed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
Shelf-life: 24 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer’s.
COMPOSITION:
Diosmin ……………………… 450 mg
Hesperidin ……………………. 50 mg
Excipients q.s………………. 1 tablet
(Wheat starch, avicel, PVP, magnesium stearate, HPMC, PVA, PEG 6000, talc, titanium dioxide, red ferric oxide, yellow ferric oxide).
DOSAGE FORM: Film coated tablet.
PRESENTATION: Box of 5 blisters x 10 tablets. Box of 10 blisters x 10 tablets.
ACTIONS: The main component of DilodinDHG is a micronized purified flavonoid fraction (diosmin, hesperidin) which is a vascular protecting agent. The drug develops its actions by inhibiting hyaluronidase, an enzyme producing capillary hyperpermeability. In case this enzyme is redundant, a hypodermic hemorrhage state occurs.
DilodinDHG acts on reducing varicose veins and venous stasis, normalizing capillary permeability and strengthening capillary resistance. DilodinDHG is used in the treatment of venous dysfunction, especially in haemorrhoids with the internal medicine method.
INDICATIONS: Treatment of the symptoms of acute haemorrhoidal attacks and chronic haemorrhoidal disease.
Treatment of the symptoms associated with venolymphatic circulatory failure e.g., footsore, heavy legs, swelling in the legs, varicose veins, post-phlebitis, cramps.
CONTRAINDICATIONS: Hypersensitivity to any components of the drug. Pregnant women and breast-feeding mothers.
PRECAUTIONS: No documents have been reported.
PREGNANCY AND LACTATION: Animal studies have shown no teratogenicity; no harmful effect has so far been reported. No data recording the drug crosses breast milk. The drug should not be used in pregnant women and breastfeeding mothers.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The drug does not affect the ability to drive and operate machinery.
INTERACTIONS: No documents have been reported.
ADVERSE EFFECTS: Gastrointestinal disturbances. Mild neurovegetative disorders have been rarely reported.
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE: No documents have been reported.
DOSAGE & ADMINISTRATION: The oral doses are divided into 2 times, in lunch and dinner.
Acute haemorrhoidal attacks: 6 tablets daily for 4 days, then 4 tablets daily for 3 days, 2 tablets daily thereafter.
Chronic hemorrhoidal disease: 2 tablets daily.
Venous insufficiency (footsore, heavy legs, swelling in the legs, varicose veins, post-phlebitis, cramps): 2 tablets daily.
Or as directed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
Shelf-life: 36 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer’s.
Keep out of the reach of children.
Read all of this leaflet carefully before you start taking this medicine.
QUALITATIVE AND QUANTITATIVE COMPOSITION:
Active ingredients:
Magnesium lactate dihydrate ……………. 470 mg
(Equivalent to magnesium 48 mg)
Vitamin B6 ……………………………………. 5 mg
Excipients: Lactose monohydrate, microcrystalline cellulose M101, wheat starch, PVP K30, sodium starch glycolate, talc, magnesium stearate, hypromellose 2910 (6cp), hypromellose 2910 (15cp), polyethylene glycol 6000, titanium dioxide
PHARMACEUTICAL FORM:
Film coated tablet.
Product description: An oval, white to off-white, film coated tablet, plain on both sides, intact edges.
THERAPEUTIC INDICATIONS:
Treatment of magnesium deficiency, isolated or associated.
POSOLOGY AND METHOD OF ADMINISTRATION:
The tablets should be swallowed with a large glass of water.
FOR ADULTS AND CHILDREN AGED MORE THAN 6 YEARS
Adults: 6 to 8 tablets per day to be divided into 2 or 3 doses taken during meals.
Children: 10 to 30 mg/kg/day (0.4 to 1.2 mmol/kg/day) or children aged more than 6 years (weighing 20 kg and more) 4 to 6 tablets per day to be divided into 2 or 3 doses taken during meals.
Treatment will be discontinued upon normalization of magnesemia.
CONTRAINDICATIONS:
Hypersensitivity to any components of the drug.
Severe renal impairment with creatinine clearance less than 30 ml/min.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
In case of severe deficiency and malabsorption, treatment should be started by the venous route.
In the case of associated calcium deficiency, it is recommended that the magnesium repletion should be carried out before calcium therapy.
Sensory neuropathy can occur when using high doses of vitamin B6 (> 200 mg/day) over a long period of time (several months or years). This is generally reversible when treatment is discontinued.
This medicine contains lactose. It is not recommended in patients with lactase deficiency, galactose intolerance, or glucose/galactose malabsorption. It is needed to consult your physician before use.
USE IN PREGNANCY AND LACTATION:
The use of magnesium can be considered during pregnancy if needed.
Magnesium or vitamin B6 taken individually is compatible with breastfeeding. It is recommended that the dose of 20 mg/day of vitamin B6 in breastfeeding women should not be exceeded.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The drug does not affect the ability to drive and operate machinery.
INTERACTIONS:
Avoid concomitant administration of magnesium with preparations containing phosphate or calcium salts (since they inhibit the absorption of magnesium in the small intestine).
When tetracycline is co-prescribed, the interval between oral doses should be at least 3 hours. Due to containing pyridoxine, concurrent administration of Magnesi-B6 and levodopa should not be recommended.
UNDESIRABLE EFFECTS:
Diarrhea, abdominal pain, skin reactions, allergic reactions.
Inform your physician about any undesirable effects occur during the treatment.
OVERDOSE:
Signs and symptoms:
Overdosage of magnesium by the oral route does not generally lead to toxic reactions in normal kidney function. Magnesium poisoning, however, can develop in patients with renal insufficiency.
The toxic effects depend on the blood level of magnesium and the signs are as follows: decreased blood pressure, nausea, vomiting, central nervous system depression, decreased reflexes, ECG abnormalities, onset of respiratory depression, coma, cardiac arrest and respiratory paralysis, anuric syndrome.
Treatment: rehydration, forced diuresis. In patients with renal insufficiency, hemodialysis or peritoneal dialysis is necessary.
PHARMACODYNAMIC PROPERTIES
ATC code: A11JB
Physiologically, magnesium is a predominantly intracellular cation. It reduces neuronal excitability and neuromuscular transmission, and is involved in many enzymatic reactions.
Approximately 50% of magnesium in the body is found in bones.
Clinically, serum magnesium concentrations: between 12 and 17 mg/L (1 to 1.4 mEq/L or 0.5 to 0.7 mmol/L) indicates a moderate magnesium deficiency. Less than 12 mg/L (1 mEq/L or 0.5 mmol/L) indicates a severe magnesium deficiency.
Magnesium deficiency can be primitive by congenital abnormalities (congenital hypomagnesemia) or secondary by inadequate intake (severe malnutrition, alcoholism, exclusive parenteral nutrition), digestive malabsorption (chronic diarrhea, digestive fistulas, hypoparathyroids), exaggerated renal losses (tubulopathy, diuretic abuse, chronic nephritis, primary hyperaldosteronism, cisplatin therapy).
PHARMACOKINETIC PROPERTIES:
After oral administration, approximately 1/3 of magnesium is absorbed in the small intestine, even soluble magnesium salts are slowly absorbed from the gastrointestinal tract. Approximately 25 – 30% of magnesium bound to plasma protein (albumin). Magnesium is eliminated mainly by the kidneys, the rate changes among individuals but is directly proportional to serum concentrations and glomerular filtration. The unabsorbed part is excreted in feces.
Vitamin B6 is readily absorbed from the gastrointestinal tract. It may be reduced in individuals with malabsorption syndrome or undergoing gastrectomy. After oral administration, vitamin B6 is mostly reserved in the liver, a smaller mount is in muscle and brain. Vitamin B6 is metabolized in the liver and red blood cells. Biological half-life is about 15 – 20 days. Vitamin B6 is excreted in urine as acid 4 – pyridoxic.
PRESENTATION: Box of 10 blisters x 10 fim coated tablets.
SHELF-LIFE: 24 months from the manufacturing date.
STORAGE CONDITIONS: Store in dry places, not exceeding 300C, protect from light.
SPECIFICATIONS: Manufacturer’s.
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COMPOSITION:
Chymotrypsin … 21 microkatals (Equivalent to 4200 USP units)
Excipients q.s …………………………………………………… 1 tablet
(Compressible sugar, magnesium stearate).
DOSAGE FORM: Tablet.
PRESENTATION: Box of 2 blisters x 10 tablets. Box of 6 blisters x 10 tablets.
PHARMACODYNAMICS:
Chymotrypsin is a proteolytic enzyme, which acts on selective catalysis of peptide bonds adjoining to aromatic amino acids. The drug is used for reducing inflammation and soft tissue oedema associated with abscess, ulcer or injuries. It also helps fluidize the upper respiratory tract secretion in patients with asthma, bronchitis, pneumopathy, and sinusitis.
PHARMACOKINETICS:
No documents have been found.
INDICATIONS:
For the treatment of oedema associated with post-operative, post-traumatic, and burns conditions.
CONTRAINDICATIONS:
Hypersensitivity to any components of the drug.
The drug should not be used in patients with the risk of alpha-1 antitrypsin deficiency: chronic obstructive pulmonary disease, alveolar emphysema, nephrotic syndrome…
PRECAUTIONS:
It is not recommended for use in cataract surgery in patients under 20 years of age.
Chymotrypsin should not be used for patients with increased vitreous pressure and opened wound or patients with congenital cataracts.
PREGNANCY AND LACTATION:
Chymotrypsin should not be given to pregnant women and nursing mothers.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
This drug does not affect the ability to drive or use machines.
INTERACTIONS:
Chymotrypsin is most often used in combination with other enzymes to enhance its treatment potential.
Chymotrypsin should not be co-administered with acetylcysteine.
Chymotrypsin should not be used together with anticoagulant agents, as it increases their effects.
ADVERSE EFFECTS:
Most common: Transient glaucoma. Used in ophthalmology: corneal edema, mild uveitis may occur.
Due to the antigenic properties of chymotrypsin, allergic reactions may occur when used at high dose.
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE:
No documents have been reported.
DOSAGE & ADMINISTRATION:
Adults: sublingual use: 1-2 tablets x 3-4 times daily.
Or as directed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
The drug is for prescriptions only.
Shelf-life: 24 months from the manufacturing date.
Storage conditions: Store in dry places; not exceeding 30oC; avoid sunlight and humidity.
Specifications: Manufacturer’s.
COMPOSITION:
Methylprednisolone …………………………………………………………. 16 mg
Excipients q.s…………………………………………………………………. 1 tablet
(Avicel M101, lactose monohydrate, dicalcium phosphate, aerosil, PVP K30, sodium lauryl sulphate, kollidon CL-M, talc, magnesium stearate)
DOSAGE FORM: Tablet.
PRESENTATION:
Box of 3 blisters x 10 tablets. Box of 10 blisters x 10 tablets.
PHARMACODYNAMICS:
Medlon contains the active ingredient Methylprednisolone, a glucocorticoid, which is an anti-inflammatory, anti-allergic agent with the capacity to profoundly inhibit the immune system. Due to methylation of prednisolone, the corticoid effect on sodium metabolism was excluded; so methylprednisolone rarely causes sodium, water retention and oedema. The anti-inflammatory activity of methylprednisolone is 20% stronger than that of prednisolone. A dose of 4 mg methylprednisolone has the same effect as 20 mg hydrocortisone.
PHARMACOKINETICS:
Bioavailability of methylprednisolone is about 80%. Peak plasma concentrations are obtained 1 – 2 hours after oral administration. It has an elimination half-life of about 3 hours. Methylprednisolone is metabolized in the liver and its metabolites are excreted in the urine.
INDICATIONS:
Treatment of inflammation and immune depression in: rheumatoid arthritis, systemic lupus erythematosus, certain angiitis, temporal arteritis and polyarteritis nodosa, sarcoidosis, bronchial asthma, chronic duodenal ulcer, hemolytic anemia, granulocytopenia, severe allergy including anaphylactic shock; in the treatment of cancers: acute leukemia, lymphoma, breast cancer, prostate cancer.
Methylprednisolone is also indicated in the treatment of primary nephrotic syndrome.
CONTRAINDICATIONS:
Hypersensitivity to methylprednisolone. Severe infections, excepting for septic shock and tuberculous meningitis. Skin injury due to virus, fungus or tuberculosis. Administration of live vaccines.
PRECAUTIONS:
Particular care is required in patients with osteoporosis, newly involved in connection of blood vessels, mental disorders, gastro-duodenal ulcer, diabetes, hypertension, heart failure; and in children during the growth phase. The common adverse effects of systemic corticosteroids may be associated in old age; treatment should be limited to the minimum dosage for the shortest period of time. Abrupt withdrawal of methylprednisolone dosage following prolonged treatment or presence of stress can lead to acute adrenal insufficiency. Large doses may affect the action of the vaccine immunization.
PREGNANCY AND LACTATION:
When administered for long periods during pregnancy, systemic corticosteroids may decrease birth weight. Corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risk. Corticosteroids do not contraindicate to nursing mothers.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The drug should be used cautiously because undesirable effects are possible in drivers, machinery operators.
INTERACTIONS:
Methylprednisolone is a cytochrome P450 enzyme inducer and is a P450 3A4 enzyme substrate; therefore, mutual inhibition of metabolism occurs with concurrent use of methylprednisolone with ciclosporin, erythromycin, phenobarbital, phenytoin, carbamazepine, ketoconazole, and rifampicin. The effect of methylprednisolone may be reduced by phenytoin, phenobarbital, rifampin and hypokalemic diuretics. Methylprednisolone may cause hyperglycemia; a higher dose of insulin should be recommended.
ADVERSE EFFECTS:
Adverse effects may occur following prolonged administration and high doses of methylprednisolone. Methylprednisolone inhibits prostaglandin synthesis, and therefore, it inactivates the actions of prostaglandin on gastrointestinal tract, including suppression of gastric acid secretion and protection of gastric mucous membrane.
Common: insomnia, excitable nerve; increased appetite, dyspepsia; hirsutism; diabetes; arthralgia; cataract, glaucoma; epistaxis.
Uncommon: dizziness, seizures, psychosis, pseudotumor cerebri, headache, mood changes, delirium, hallucination, cheeriness; edema, hypertension; acne, skin atrophy, bruise, hyperchromasia; Cushing’s syndrome; stomach ulcers, nausea, vomiting, abdominal distention, ulcerative esophagitis, pancreatitis; muscle weakness, osteoporosis, fractures; hypersensitive reactions.
Inform a physician about any adverse effects occur during the treatment.
OVERDOSE:
Symptoms of overdose associated with prolonged use include Cushing’s syndrome, muscle weakness, osteoporosis, adrenal suppression. Temporary discontinuation or termination of the drug should be considered.
DOSAGE & ADMINISTRATION:
Dosage requirements depend on the condition being treated and response of the patient. The initial dose should be 6 – 40 mg of methylprednisolone daily. A necessary dosage to maintain a desired therapeutic effect is lower than that to obtain an initial effect. The proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached.
In long-term treatment with large dose, the drug should be indicated in every other day when the diseases being controlled. This minimizes certain undesirable effects due to recovery time among doses.
In this therapy, methylprednisolone is given single morning dose every two days according to natural secretion time of glucocorticoids.
Acute asthma: 32 – 48 mg/day for 5 days. An additional treatment with a lower dose should be applied within one week. If the acute course disappears, the dosage should be reduced gradually and promptly.
Acute course of rheumatoid arthritis: 16 – 32 mg/day. Thereafter, the dosage should be reduced gradually and promptly.
Acute course of chronic ulcerative colitis: 8 – 24 mg/day.
Primary nephrotic syndrome: The initial dose should be 0.8 – 1.6 mg/ kg/day for 6 weeks, then reducing gradually the dosage for 6 to 8 weeks.
Hemolytic anemia due to immunity: 64 mg/day for at least 6 – 8 weeks.
Or as directed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
This drug is for prescriptions only.
Shelf-life: 24 months from the manufacturing date.
Storage conditions: Store in dry places; not exceeding 30oC, protect from light.
Specifications: Manufacturer’s.
COMPOSITION:
Acyclovir ………………………… 800 mg
Excipients q.s…………………… 1 tablet
(Microcrystalline cellulose M101, wheat starch, ponceau, PVP K30, colloidal silicon dioxide, magnesium stearate, talc).
DOSAGE FORM: Tablet.
PRESENTATION: Box of 3 blisters x 10 tablets.
PHARMACODYNAMICS:
Acyclovir is similar to nucleoside. It interferes DNA synthesis and inhibits selectively viral replication, resulting in not affecting the metabolism of normal cells. Acyclovir is potently active against Herpes simplex virus type 1 (HSV-1) and less active against Herpes simplex virus type 2 (HSV-2) and Varicella zoster virus (VZV), cytomegalovirus (CMV).
PHARMACOKINETICS:
Oral bioavailability of acyclovir is about 20%. Oral acyclovir is mainly absorbed by the GI tract; the influence of food on the absorption of acyclovir was not apparent. Acyclovir is widely distributed in body fluids and organs including brain, kidney, lung, intestine, liver, spleen, uterus, mucosa, vaginal mucosa, tears, aqueous humor, seminal fluid, encephalospinal fluid. Plasma protein binding is relatively low (9 to 33%). Peak plasma concentrations of acyclovir usually occur with 1.5 to 2 hours. The elimination half-life of acyclovir is approximately 2 to 3 hours. Acyclovir is excreted principally in the kidneys as unchanged; a small amount of acyclovir is metabolized by the liver.
INDICATIONS:
reatment of initial and recurrent infections due to Herpes simplex virus type 1 and type 2 on skin and mucosa, Herpes simplex encephalitis.
Treatment of acute Herpes zoster infections (shingles), ocular shingles, pneumonia due to Herpes zoster in adults.
Treatment of initial and recurrent infections of genital Herpes.
Treatment of haemorrhagic chickenpox, chickenpox in immunodeficiency patients, chickenpox in newborn baby.
CONTRAINDICATIONS:
Hypersensitivity to any components of the drug.
PRECAUTIONS:
Renal failure has been observed with acyclovir therapy.
Caution should also be exercised when administering acyclovir to patients receiving potentially nephrotoxic agents.
Do not exceed the prescribed doses and the treatment period of time.
PREGNANCY AND LACTATION:
Acyclovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Acyclovir concentrations have been documented in breast milk. It should be administered to a nursing mother with caution.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The drug does not affect the ability to drive and use machinery.
INTERACTIONS:
Concurrent use of zidovudine and acyclovir may cause states of doze and deep sleep.
Probenecid is reported to inhibit the renal elimination of acyclovir, reduce the uric excretion and the purification of acyclovir.
Amphotericin B and ketoconazole enhance the antiviral effect of acyclovir.
ADVERSE EFFECTS:
Side effects in patients treated short-term with acyclovir are nausea, vomiting. Long-term treatment over 1 year has the potential for nausea, vomiting, diarrhea, colic, rash, headache (<5% of patients).
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE:
Symptoms: Precipitation of acyclovir in renal tubules may occur when renal concentrations is excreted the solubility (2.5 mg/ml) or the serum creatinine is elevated. Adverse events that have been also reported in association with overdosage include renal failure, excitement, anxiety, convulsion, palpitation, hypertension, and dysuria.
Management: Hemodialysis is advised until recovery of renal function. The drug should be discontinued and patients should receive fluids and electrolytes.
DOSAGE & ADMINISTRATION:
For treatment of Herpes simplex infections:
– Adults and children aged > 2 years: oral dose of 200 mg (400 mg in immunodeficiency patients) 5 times daily every 4 hours for 5 – 10 days.
For suppression of recurrent Herpes simplex in immunocompromised patients, visceral transplant patients using the hypo-immune drugs, HIV-infected person, chemotherapy-treating individuals.
– Adults and children aged > 2 years: oral dose of 200 – 400 mg, 4 times daily.
For treatment of chickenpox and shingles:
– Adults: oral dose of 800 mg 5 times daily, for 7 days.
– Children: oral dose of 20 mg/ kg body-weight (maximum of 800 mg), 4 times daily for 5 days.
For patients with renal impairment: The dose for patients with renal impairment associated with HSV or Varicella zoster infections is similar to that of normal patients. However, the dose should be modified as follows:
– Creatinine clearance of 10 – 25 ml/ min: taking every 8 hours.
– Creatinine clearance of below 10 ml/ min: taking every 12 hours.
Or as directed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
This drug is for prescription only.
Shelf-life: 36 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer’s.
COMPOSITION:
Spiramycin ………………………………………………………………. 3,000,000 IU
Excipients q.s…………………………………………………………………… 1 tablet
(Aerosil, tapioca starch, talc, magnesium stearate, sodium starch glycolate, HPMC, PEG 6000, titanium dioxide).
DOSAGE FORM: Film coated tablets
PRESENTATION: Box of 2 blisters x 5 tablets.
PHARMACODYNAMICS:
Rovas contains Spiramycin which is a macrolide antibiotic. Spiramycin is bacteriostatic at serum concentrations but may be bactericidal at tissue concentrations. Mechanism of action of spiramycin is to bind reversibly to the 50S subunits of bacterial ribosome resulting in inhibition of protein synthesis. Spiramycin is active against Gram-positive organisms, Coccus spp. including Staphylococcus, Pneumococcus, Meningococcus, etc.
PHARMACOKINETICS:
Spiramycin is incompletely absorbed from the gastrointestinal tract. Drug absorption is approximately 20 – 50% of the dose. Peak plasma concentrations attained within 2 – 4 hrs after oral administration. Peak blood concentrations of a single dose may maintain 4 – 6 hrs. Bioavailability of spiramycin may be significantly reduced when the presence of food is in the stomach. Cmax is decreased by 70% and tmax is delayed by 2 hours in the presence of food. Spiramycin is widely distributed in the body. Spiramycin achieves high concentrations in lung, tonsils, bronchi, and sinuses. Penetration of spiramycin into cerebrospinal fluid is reported to be poor. The mean half-life is 5 to 8 hours. Spiramycin is mainly excreted in the bile. Only 2% of total drug is found in the urine after 36 hrs of oral administration.
INDICATIONS:
Spiramycin is suggested to be the second choice in treatment of respiratory tract infections, skin and genital infections caused by susceptible to bacteria.
Preventive treatment of meningitis caused by Meningococcus when patients contra-indicated in the prescription of rifampicin
Prevention of innate toxoplasmosis during pregnant period.
Prophylaxis of recurrences of acute rheumatism in penicillin-allergic patients.
CONTRAINDICATIONS:
A known history of hypersensitivity to spiramycin, erythromycin.
PRECAUTIONS:
The drug should be used with caution in patients with hepatic dysfunction because it may cause hepatotoxicity.
PREGNANCY AND LACTATION:
Spiramycin crosses the placenta; however, fetal blood concentrations are lower than maternal serum concentrations. Spiramycin does not cause bad effects in pregnant women. High concentrations are distributed into breast milk; therefore, breast-feeding is not recommended to women taking spiramycin.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The effect of spiramycin on the ability to drive, use machines is rarely reported.
INTERACTIONS:
Concomitant use of spiramycin with oral contraceptives causes ineffective contraception.
ADVERSE EFFECTS:
Common: nausea, vomiting, diarrhea, dyspepsia (following oral route).
Uncommon: General disorders: fatigue, nosebleed, sweating, chest pains; transient paresthesia, unsteadiness, muscle and joint contractures or pains, burning sensation, flushing (following intravenous injection); Gastrointestinal disorders: acute colitis; Skin disorders: skin rash, urticaria.
Rare: anaphylactic reactions, surinfections due to prolonged use of spiramycin.
Inform your physician about any adverse effects occur during the treatment.
OVERDOSE:
No documents have been reported. In the event of overdosage, inform your doctor immediately.
DOSAGE & ADMINISTRATION:
Treatment dose:
Adults and children aged > 12 years: oral dose of 3,000,000 IU 3 times for 24 hours (1 tablet 3 times daily).
Prevention of meningitis caused by Meningococcus:
Adults and children aged > 12 years: oral dose of 3,000,000 IU every 12 hours (1 tablet twice daily).
Prophylaxis of innate toxoplasmosis in pregnancy:
Oral dose of 9,000,000 IU/day (3 tablets/day), in divided doses for 3 weeks. The dosage should be repeated every 2 weeks.
Alternate or coordinate administration with pyrimethamine/sulfonamide therapy should be given to get a better result.
Bioavailability of spiramycin may be decreased when the presence of food is in the stomach; so the drug should be taken at least 2 hours before a meal or 3 hours after a meal.
The therapy must be completely pursued.
Or as directed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
This drug is for prescriptions only.
Shelf-life: 36 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer’s.
Prescription only.
Read the instruction thoroughly before use.
Please inform your doctor of all undesirable effects upon drug administration.
Keep out of reach of children.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient: Azithromycin (as azithromycin dihydrate) … 500 mg
Excipients: Dibasic calcium phosphate dihydrate, pregelatinized starch, hypromellose 2208, croscarmellose sodium, magnesium stearate, sodium laurilsulfate, hypromellose 2910 (6cp), hypromellose 2910 (15cp), polyethylene glycol 6000, titanium dioxide, talc.
PHARMACEUTICAL FORM: Film coated tablet.
Product description: A white to off-white, oval, film-coated tablet, a plain on one side and a score line on the other, intact edges.
THERAPEUTIC INDICATIONS
Azithromycin is indicated for infections caused by susceptible organisms; in lower respiratory tract infections including bronchitis and pneumonia, in odontostomatological infections, in skin and soft tissue infections, in acute otitis media and in upper respiratory tract infections including sinusitis and pharyngitis/tonsillitis. (Penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes pharyngitis, including the prophylaxis of rheumatic fever. Azithromycin is generally effective in the eradication of streptococci from the oropharynx; however, data establishing the efficacy of azithromycin and the subsequent prevention of rheumatic fever are not available at present).
In sexually transmitted diseases in men and women, azithromycin is indicated for the treatment of uncomplicated genital infections due to Chlamydia trachomatis. It is also indicated for the treatment of chancroid due to Haemophilus ducreyi; and uncomplicated genital infections due to non-multiresistant Neisseria gonorrhoea; concurrent infection with Treponema pallidum should be excluded.
Azithromycin is indicated, either alone or in combination with rifabutin, for prophylaxis against Mycobacterium avium-intracellulare complex (MAC) infection, an opportunistic infection prevalent in patients with advanced human immunodeficiency virus (HIV).
Azithromycin is indicated in combination with ethambutol for the treatment of disseminated MAC (DMAC) infection in patients with advanced HIV infection.
POSOLOGY AND METHOD OF ADMINISTRATION
Oral azithromycin should be administered as a single daily dose. Duration of the treatment for the different infection diseases is given below. Azithromycin tablets can be taken with or without food.
In adults
For the treatment of sexually transmitted diseases caused by Chlamydia trachomatis and Haemophilus ducreyi, the dose is 1000 mg as a single oral dose. For susceptible Neisseria gonorrhoea, the recommended dose is 1000 mg or 2000 mg of azithromycin as a single dose in combination with 250 mg or 500 mg ceftriaxone according to local clinical treatment guidelines. For patients who are allergic to penicillin and/or cephalosporins, prescribers should consult local treatment guidelines.
For prophylaxis against MAC infections in patients infected with the human immunodeficiency virus (HIV), the dose is 1200 mg once per week.
For the treatment of DMAC infections in patients with advanced HIV infection, the recommended dose is 600 mg once a day. Azithromycin should be administered in combination with other antimycobacterial agents that have shown in vitro activity against MAC, such as ethambutol at the approved dose. For all other indications in which the oral formulation is administered, the total dosage of 1500 mg should be given as 500 mg daily for 3 days. As an alternative, the same total dose can be given over 5 days with 500 mg given on Day 1, then 250 mg daily on Days 2 to 5.
In children: The maximum recommended total dose for any treatment is 1500 mg for children.
| Weight (kg) | 3-day regimen | 5-day regimen |
| >45 | Dose as per adults. | Dose as per adults. |
Azithromycin tablets should only be administered to children weighing more than 45 kg.
In the elderly: The same dosage as in adult patients is used in the elderly. Elderly patients may be more susceptible to the development of torsades de pointes arrhythmia than younger patients (see section Special Warnings and Precautions for use).
In patients with renal impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10 – 80 ml/min). Caution should be exercised when azithromycin is administered to patients with severe renal impairment (GFR < 10 ml/min) (see section Special Warnings and Precautions for use and section Pharmacokinetic properties).
In patients with hepatic impairment: The same dosage as in patients with normal hepatic function may be used in patients with mild to moderate hepatic impairment (see section Special Warnings and Precautions for use).
Or as directed by a physician.
CONTRAINDICATIONS
The use of this product is contraindicated in patients with a hypersensitivity to azithromycin, erythromycin, any other macrolide or ketolide antibiotic, or to any of the excipients listed in section Qualitative and Quantitative Composition.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Hypersensitivity
As with erythromycin and other macrolides, rare serious allergic reactions, including angiooedema and anaphylaxis (rarely fatal), dermatologic reactions, including acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (rarely fatal) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment.
If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.
Hepatotoxicity
Since the liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease.
Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.
Infantile hypertrophic pyloric stenosis (IHPS)
Following the use of azithromycin in neonates (treatment up to 42 days of life), infantile hypertrophic pyloric stenosis (IHPS) has been reported. Parents and caregivers should be informed to contact their physician if vomiting or irritability with feeding occurs.
Ergot derivatives
In patients receiving ergot derivatives, ergotism has been precipitated by co-administration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be co-administered.
Superinfection
As with any antibiotic preparation, observation for signs of superinfection with non-susceptible organisms, including fungi is recommended.
Clostridium difficile associated diarrhoea
Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.
Renal impairment
In patients with severe renal impairment (GFR < 10 ml/min), a 33% increase in systemic exposure to azithromycin was observed (see section Pharmacokinetic properties).
Prolongation of the QT interval
Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with macrolides, including azithromycin (see section Undesirable effects). Prescribers should consider the risk of QT prolongation, which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including:
Myasthenia gravis
Exacerbations of the symptoms of myasthenia gravis have been reported in patients receiving azithromycin therapy.
Excipients
This medicine contains less than 1 mmol sodium (23 mg) per sachet, that is to say essentially “sodium-free”.
USE IN PREGNANCY AND LACTATION
Pregnancy
Animal reproduction studies have been performed at doses up to moderately maternally toxic dose concentrations. In these studies, no evidence of harm to the fetus due to azithromycin was found. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, azithromycin should be used during pregnancy only if clearly needed.
Lactation
Azithromycin has been reported to be secreted into human breast milk, but there are no adequate and well-controlled clinical studies in nursing women that have characterized the pharmacokinetics of azithromycin excretion into human breast milk. Azithromycin should be used with caution in breastfeeding mothers.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINE
There is no evidence to suggest that azithromycin may have an effect on a patient’s ability to drive or operate machinery. However, undesirable effects such as dizziness, seizures, vertigo, drowsiness and syncope have been reported during azithromycin therapy and can affect the ability to drive and use machines.
INTERACTIONS
Antacids: In a pharmacokinetic study investigating the effects of simultaneous administration of antacid with azithromycin, no effect on overall bioavailability was seen, although peak serum concentrations were reduced by approximately 24%. In patients receiving both azithromycin and antacids, the drugs should not be taken simultaneously.
Cetirizine: In healthy volunteers, co-administration of a 5-day regimen of azithromycin with 20 mg cetirizine at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.
Didanosine (Dideoxyinosine): Co-administration of 1200 mg/day azithromycin with 400 mg/day didanosine in six HIV-positive subjects did not appear to affect the steady state pharmacokinetics of didanosine.
Digoxin: Concomitant administration of macrolide antibiotics, including azithromycin with P-glycoprotein substrates such as digoxin, has been reported to result in increased serum levels of the P-glycoprotein substrate. Therefore, if azithromycin and P-glycoprotein substrates such as digoxin are administered concomitantly, the possibility of elevated serum digoxin concentrations should be considered. Clinical monitoring, and possibly serum digoxin levels, during treatment with azithromycin and after its discontinuation are necessary.
Ergot: There is a theoretical possibility of interaction between azithromycin and ergot derivatives (see section Special Warnings and Precautions for use).
Zidovudine: Single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients.
Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with azithromycin.
Pharmacokinetic studies have been conducted between azithromycin and the following drugs known to undergo significant cytochrome P450-mediated metabolism.
Atorvastatin: Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay). However, post-marketing cases of rhabdomyolysis in patients receiving azithromycin with statins have been reported.
Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of carbamazepine or its active metabolite in patients receiving concomitant azithromycin.
Cimetidine: In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, on the pharmacokinetics of azithromycin, no alteration of azithromycin pharmacokinetics was seen.
Coumarin-type oral anticoagulants: In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single dose of 15 mg warfarin administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated anticoagulation subsequent to co-administration of azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when azithromycin is used in patients receiving coumarin-type oral anticoagulants.
Cyclosporin: In a pharmacokinetic study with healthy volunteers that were administered a 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of cyclosporin, the resulting cyclosporin Cmax and AUC0-5 were found to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, cyclosporin levels should be monitored and the dose adjusted accordingly.
Efavirenz: Co-administration of a single dose of 600 mg azithromycin and 400 mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.
Fluconazole: Co-administration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the co-administration of fluconazole, however, a clinically insignificant decrease in Cmax (18%) of azithromycin was observed.
Indinavir: Co-administration of a single dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.
Methylprednisolone: In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.
Midazolam: In healthy volunteers, co-administration of azithromycin 500 mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single dose of 15 mg midazolam.
Nelfinavir: Co-administration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment was required.
Rifabutin: Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either medicinal product. Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established (see section Undesirable effects).
Sildenafil: In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolite.
Terfenadine: Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and terfenadine. There have been rare cases reported where the possibility of such an interaction could not be entirely excluded; however, there was no specific evidence that such an interaction had occurred.
Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers.
Triazolam: In 14 healthy volunteers, co-administration of 500 mg azithromycin on Day 1 and 250 mg on Day 2 with 0.125 mg triazolam on Day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.
Trimethoprim/sulfamethoxazole: Co-administration of trimethoprim/sulfamethoxazole (160 mg/800 mg) for 7 days with 1200 mg azithromycin on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.
UNDESIRABLE EFFECTS
Azithromycin is well tolerated with a low incidence of side effects.
In clinical trials, the following undesirable effects have been reported:
Blood and lymphatic system disorders: Transient episodes of mild neutropenia have occasionally been observed in clinical trials.
Ear and labyrinth disorders: Hearing impairment (including hearing loss, deafness and/or tinnitus) has been reported in some patients receiving azithromycin. Many of these have been associated with prolonged use of high doses in investigational studies. In those cases where follow-up information was available, the majority of these events were reversible.
Gastrointestinal disorders: Nausea, vomiting, diarrhea, loose stools, abdominal discomfort (pain/cramps), and flatulence.
Hepatobiliary disorders: Abnormal liver function.
Skin and subcutaneous tissue disorders: Allergic reactions including rash and angioedema.
The following undesirable effects have been reported in association with DMAC prophylaxis and treatment clinical trials:
The most frequent (>5% in any treatment group) adverse reactions in HIV-infected patients receiving azithromycin for prophylaxis for DMAC were diarrhea, abdominal pain, nausea, loose stools, flatulence, vomiting, dyspepsia, rash, pruritus, headache, and arthralgia.
When 600 mg azithromycin is given daily for the treatment of DMAC infection for prolonged periods, the most frequently reported treatment-related side effects are abdominal pain, nausea, vomiting, diarrhea, flatulence, headache, abnormal vision, and hearing impairment.
In post-marketing experience, the following additional undesirable effects have been reported:
Infections and infestations: Moniliasis and vaginitis.
Blood and lymphatic system disorders: Thrombocytopenia.
Immune system disorders: Anaphylaxis (rarely fatal) (see section Special Warnings and Precautions for use).
Metabolism and nutrition disorders: Anorexia.
Psychiatric disorders: Aggressive reaction, nervousness, agitation, and anxiety.
Nervous system disorders: Dizziness, convulsions, headache, hyperactivity, hypoesthesia, paresthesia, somnolence, and syncope. There have been rare reports of taste/smell perversion and/or loss.
Ear and labyrinth disorders: Deafness, tinnitus, hearing impaired, and vertigo.
Cardiac disorders: Palpitations and arrhythmias including ventricular tachycardia have been reported. There have been rare reports of QT prolongation and torsades de pointes (see section Special Warnings and Precautions for use).
Vascular disorders: Hypotension.
Gastrointestinal disorders: Vomiting/diarrhea (rarely resulting in dehydration), dyspepsia, constipation, pseudomembranous colitis, pancreatitis, and rare reports of tongue discoloration.
Hepatobiliary disorders: Hepatitis and cholestatic jaundice have been reported, as well as rare cases of hepatic necrosis and hepatic failure, which have rarely resulted in death (see section Special Warnings and Precautions for use, Hepatotoxity).
Skin and subcutaneous tissue disorders: Allergic reactions including pruritus, rash, photosensitivity, urticaria, oedema, and angioedema. Rarely, serious cutaneous adverse reactions including erythrema multiforme, acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported.
Musculoskeletal and connective tissue disorders: Arthralgia.
Renal and urinary disorders: Interstitial nephritis and acute renal failure.
General disorders: Asthenia, fatigue, and malaise.
Please inform your doctor of all undesirable effects upon drug administration.
OVERDOSE: Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. In the event of overdosage, general symptomatic and supportive measures are indicated as required.
PHARMACODYNAMIC PROPERTIES
Phamacotherapeutic group: Macrolides.
ATC code: J01FA10
Mechanism of action
Azithromycin is the first of a subclass of macrolide antibiotics, known as azalides, and is chemically different from erythromycin. Chemically it is derived by insertion of a nitrogen atom into the lactone ring of erythromycin A. The chemical name of azithromycin is 9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A. The molecular weight is 749.0.
Azithromycin binds to the 23S rRNA of the 50S ribosomal subunit. It blocks protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit.
Cardiac electrophysiology
QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1000 mg) alone or in combination with azithromycin (500 mg, 1000 mg, and 1500 mg once daily). Co-administration of azithromycin increased the QTc interval in a dose- and concentration-dependent manner. In comparison to chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14) ms with the co-administration of 500 mg, 1000 mg and 1500 mg azithromycin, respectively.
Mechanism of resistance
The two most frequently encountered mechanisms of resistance to macrolides, including azithromycin, are target modification (most often by methylation of 23S rRNA) and active efflux. The occurrence of these resistance mechanisms varies from species to species and, within a species, the frequency of resistance varies by geographical location.
The most important ribosomal modification that determines reduced binding of macrolides is post-transcriptional (N6)-dimethylation of adenine at nucleotide A2058 (Escherichia coli numbering system) of the 23S rRNA by methylases encoded by erm (erythromycin ribosome methylase) genes. Ribosomal modifications often determine cross-resistance (MLSB phenotype) to other classes of antibiotics whose ribosomal binding sites overlap those of the macrolides: the lincosamides (including clindamycin), and the streptogramin B (which include, for example, the quinupristin component of quinupristin/dalfopristin). Different erm genes are present in different bacterial species, in particular Streptococci and Staphylococci. Susceptibility to macrolides can also be affected by less frequently encountered mutational changes in nucleotides A2058 and A2059, and at some other positions of 23S rRNA, or in the large subunit ribosomal proteins L4 and L22.
Efflux pumps occur in a number of species, including Gram-negatives, such as Haemophilus influenza (where they may determine higher minimal inhibitory concentrations [MICs]) and Staphylococci. In Streptococci and Enterococci, an efflux pump that recognises 14- and 15-membered macrolides (which include, respectively, erythromycin and azithromycin) is encodedby mef (A) genes.
Methodology for determining the in vitro susceptibility of bacteria to azithromycin
Susceptibility testing should be conducted using standardized laboratory methods, such as those described by the Clinical and Laboratory Standards Institute (CLSI). These include dilution methods (MIC determination) and disk susceptibility methods. Both CLSI and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) provide interpretive criteria for these methods.
Based on a number of studies, it is recommended that the in vitro activity of azithromycin be tested in ambient air to ensure physiological pH of the growth medium. Elevated CO2 tensions, as often used for Streptococci and anaerobes, and occasionally for other species, result in a reduction in the pH of the medium. This has a greater adverse effect on the apparent potency of azithromycin than on that of other macrolides.
The CLSI susceptibility breakpoints, based on broth microdilution or agar dilution testing, with incubation in ambient air, are given in the table below.
CLSI dilution susceptibility interpretive criteria
| Broth microdilution MIC (mg/L) |
|||
| Organism | Susceptible | Intermediate | Resistant |
| Haemophilus species | <=4 | – | _b |
| Moraxella catarrhalis | <=0,25 | – | – |
| Neisseria meningitidis | <=2 | – | _b |
| Staphylococcus aureus | <=2 | 4 | =>8 |
| Streptococcia | <=0,5 | 1 | =>2 |
a Includes Streptococcus pneumoniae, β-haemolytic streptococci and viridans streptococci.
b The current absence of data on resistant strains precludes defining any category other than susceptible. If strains yield MIC results other than susceptible, they should be submitted to a reference laboratory for further testing.
Incubation in ambient air.
CLSI = Clinical and Laboratory Standards Institute; MIC = Minimal inhibitory concentration.
Source: CLSI, 2012. CLSI, 2010.
Susceptibility can also be determined by the disk diffusion method, measuring inhibition zone diameters after incubation in ambient air. Susceptibility disks contain 15 µg of azithromycin. Interpretive criteria for inhibition zones, established by the CLSI on the basis of their correlation with MIC susceptibility categories, are listed in the table below.
CLSI disk zone interpretive criteria
| Disk inhibition zone diameter (mm) |
|||
| Organism | Susceptible | Intermediate | Resistant |
| Haemophilus species | ≥ 12 | – | – |
| Moraxella catarrhalis | ≥ 26 | – | – |
| Neisseria meningitidis | ≥ 20 | – | – |
| Staphylococcus aureus | ≥ 18 | 14-17 | ≤ 13 |
| Streptococcia | ≥ 18 | 14-17 | ≤ 13 |
a Includes Streptococcus pneumoniae, β-haemolytic streptococci and viridans streptococci.
Incubation in ambient air.
CLSI = Clinical and Laboratory Standards Institute; mm = Millimeters.
Source: CLSI, 2012. CLSI, 2010.
The validity of both the dilution and disk diffusion test methods should be verified using quality control (QC) strains, as indicated by the CLSI. Acceptable limits when testing azithromycin against these organisms are listed in the table below.
Quality control ranges for azithromycin susceptibility tests (CLSI)
| Broth microdilution MIC | |
| Organism | Quality control range (mg/L azithromycin) |
| Haemophilus influenzae ATCC 49247 | 1 – 4 |
| Staphylococcus aureus ATCC 29213 | 0,5 – 2 |
| Streptococcus pneumoniae ATCC 49619 | 0,06 – 0,25 |
| Disk inhibition zone diameter (15 mg disk) | |
| Organism | Quality control range (mm) |
| Haemophilus influenzae ATCC 49247 | 13 – 21 |
| Staphylococcus aureus ATCC 25923 | 21 – 26 |
| Streptococcus pneumoniae ATCC 49619 | 19 – 25 |
Incubation in ambient air.
CLSI = Clinical and Laboratory Standards Institute; MIC = Minimal inhibitory concentration; mm = Millimeters.
Source: CLSI, 2012.
European Committee on Antimicrobial Susceptibility Testing (EUCAST) has also established susceptibility breakpoints for azithromycin based on MIC determination. The EUCAST susceptibility criteria are listed in the table below.
EUCAST Susceptibility breakpoints for azithromycin
| MIC (mg/L) | ||
| Susceptible | Resistant | |
| Staphylococcus species | ≤ 1 | > 2 |
| Streptococcus pneumoniae | ≤ 1 | > 2 |
| β-haemolytic Streptococci a | ≤ 1 | > 2 |
| Haemophilus influenzae | ≤ 1 | > 2 |
| Moraxella catarrhalis | ≤ 1 | > 2 |
| Neisseria gonorrhoeae | ≤ 1 | > 2 |
a Includes Groups A, B, C, G.
EUCAST = European Committee on Antimicrobial Susceptibility Testing; MIC = Minimal inhibitory concentration.
Source: EUCAST website.
EUCAST clinical breakpoint tablet v. 2.0, valid from 01-01-2012
Antibacterial spectrum
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Azithromycin demonstrates cross-resistance with erythromycin-resistant Gram-positive isolates. As discussed above, some ribosomal modifications determine cross-resistance with other classes of antibiotics whose ribosomal binding sites overlap those of the macrolides: the lincosamides (including clindamycin) and the streptogramin B (which include, for example, the quinupristin component of quinupristin/dalfopristin). A decrease in macrolide susceptibility over time has been noted in particular in Streptococcus pneumoniae and Staphylococcus aureus, and has also been observed in viridans streptococci and Streptococcus agalactiae.
Organisms that are commonly susceptible to azithromycin include:
Facultatively anaerobic and aerobic Gram-positive bacteria (erythromycin-susceptible isolates): S. aureus, Streptococcus agalactiae*, S. pneumonia*, Streptococcus pyogenes*, other β-haemolytic streptococci (Groups C, F, G), and viridans Streptococci. Macrolide-resistant isolates are encountered relatively frequently among anaerobic and facultative Gram-positive bacteria and aerobic bacteria, in particular among methicillin-resistant S. aureus (MRSA) and penicillin-resistant S. pneumoniae (PRSP).
Facultatively anaerobic and aerobic Gram-negative bacteria: Bordetella pertussis, Campylobacter jejuni, Haemophilus ducreyi*, Haemophilus influenzae*, Haemophilus parainfluenzae*, Legionella pneumophila, Moraxella catarrhalis*, and Neisseria gonorrhoeae*. Pseudomonas spp. and most Enterobacteriaceae are inherently resistant to azithromycin, although azithromycin has been used to treat Salmonella enterica infections.
Anaerobes: Clostridium perfringens, Peptostreptococcus spp. and Prevotella bivia.
Other bacterial species: Borrelia burgdorferi, Chlamydia trachomatis, Chlamydophila pneumoniae*, Mycoplasma pneumoniae*, Treponema pallidum, and Ureaplasma urealyticum.
Opportunistic pathogens associated with HIV infection: MAC* and the eukaryotic microorganisms Pneumocystis jirovecii and Toxoplasma gondii.
* The efficacy of azithromycin against the indicated species has been demonstrated in clinical trials.
PHARMACOKINETIC PROPERTIES
Absorption: Following oral administration in humans, azithromycin is widely distributed throughout the body; bioavailability is approximately 37%. The time taken to peak plasma levels is 2 to 3 hours.
Distribution: In animal studies, high azithromycin concentrations have been observed in phatocytes. In experimental models, higher concentrations of azithromycin are released during active phagocytosis than from non-stimulated phagocytes. In animal models, this results in high concentrations of azithromycin being delivered to the site of infection.
Pharmacokinetic studies in humans have shown markedly higher azithromycin levels in tissues than in plasma (up to 50 times the maximum observed concentration in plasma), indicating that the drug is heavily tissue bound. Concentrations in target tissues, such as lung, tonsil and prostate, exceed the MIC90 for likely pathogens after a single dose of 500 mg.
Following oral administration of daily dose of 600 mg azithromycin, Cmax was 0.33 µg/ml and 0.55 µg/ml at Day 1 and Day 22, respectively. Mean peak concentrations observed in leukocytes, the major site of disseminated MAC infection, were 252 µg/ml (± 49%) and remained above 146 µg/ml (± 33%) for 24 hours at steady state.
Metabolism: The majority of systemically available azithromycin is excreted unchanged in the bile. In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed.
Elimination: Plasma terminal elimination half-life closely reflects the tissue depletion half-life of 2 to 4 days. Approximately 12% of an intravenously administered dose is excreted unchanged in the urine within the following three days, the majority in the first 24 hours. Biliary excretion of azithromycin is a major route of elimination for unchanged drug following oral administration. Very high concentrations of unchanged drug have been found in human bile, together with 10 metabolites were through by N- and O- demethylation, hydroxylation of the desosamine and aglycone rings and cleavage of cladinose conjugate. Comparison of HPLC and microbiological assays in tissues suggests the metabolites play no part in the microbiological activity of azithromycin.
Pharmacokinetics in special patient groups
Elderly: In elderly volunteers (>65 years), slightly higher AUC values were seen after a 5-day regime than in young volunteers (<40 years), but these are not considered clinically significant, and hence no dose adjustment is recommended.
Renal impairment: The pharmacokinetics of azithromycin in subjects with mild and moderate renal impairment (GFR 10 – 80 ml/min) were not affected following a single 1 gram dose of immediate-release azithromycin. Statistically significant differences in AUC0-120 (8.8 µg.h/ml vs. 11.7 µg.h/ml), Cmax (1.0 µg/ml vs. 1.6 µg/ml) and CLr (2.3 ml/min/kg vs. 0.2 ml/min/kg) were observed between the group with severe renal impairment (GFR < 10 ml/min) and the group with normal renal function.
Hepatic impairment: In patients with mild (Class A) to moderate (Class B) hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of azithromycin compared to those with normal hepatic function. In these patients, urinary clearance of azithromycin appears to increase, perhaps to compensate for reduced hepatic clearance.
Preclinical safety data
Phospholipidosis (intracellular phospholipid accumulation) has been observed in several tissues (e.g. eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) of mice, rats, and dogs given multiple doses of azithromycin. Phospholipidosis has been observed to a similar extent in the tissues of neonatal rats and dogs. The effect has been shown to be reversible after cessation of azithromycin treatment. The significance of the finding for animals and humans is unknown.
In fertility studies conducted in rats, reduced pregnancy rates were noted following administration of azithromycin. The relevance of this finding to humans is unknown.
PRESENTATION: Box of 3 blisters x 10 film coated tablets
SHELF-LIFE: 36 months from the manufacturing date.
STORAGE CONDITIONS: Store in dry places, not exceeding 300C, protect from light.
SPECIFICATIONS: Manufacturer’s.
Keep out of reach of children.
Read all of this leaflet carefully before you start taking this medicine.
The drug is for prescription only.
QUALITATIVE AND QUANTITATIVE COMPOSITION:
Active ingredients:
Domperidone ……………………………… 10 mg
Excipients:
Lactose, wheat starch, sodium starch glycolate, aerosil, magnesium stearate, PVP K30, HPMC, PEG 6000, titanium dioxide, talc.
PHARMACEUTICAL FORM: Film coated tablet.
Product description: A white to off-white, round, film-coated tablet, plain on both sides, intact edges.
THERAPEUTIC INDICATIONS:
Modom’S is indicated for the relief of the symptoms of nausea and vomiting.
POSOLOGY AND METHOD OF ADMINISTRATION:
Modom’S should be used at the lowest effective dose for the shortest duration necessary to control nausea and vomiting.
It is recommended to take oral domperidone tablets before meals. If taken after meals, absorption of the drug is somewhat delayed.
Patients should try to take each dose at scheduled time. If a scheduled dose is missed, the missed dose should be omitted and the usual dosing schedule resumed. The dose should not be doubled to make up for a missed dose.
Usually, the maximum treatment duration should not exceed one week.
Adults and adolescents (12 years of age and older and weighing 35 kg or more):
One 10mg tablet up to three times per day with maximum dose of 30 mg per day.
Neonates, infants, children (less than 12 years of age) and adolescents weighing less than 35 kg.
Due to the need for accurate dosing, domperidone tablets are unsuitable for use in children and adolescents weighing less than 35 kg.
Hepatic impairment:
Modom’S is contraindicated in moderate or severe hepatic impairment (see Contraindications). Dose modification in mild hepatic impairment is however not needed.
Renal impairment:
Since the elimination half-life of domperidone is prolonged in severe renal impairment, on repeated administration, the dosing frequency of Modom’S should be reduced to once or twice daily depending on the severity of the impairment.
Or as directed by a physician.
CONTRAINDICATIONS:
Domperidone is contraindicated in the following situations:
In patients with vomiting after surgery. In patients with gastro-intestinal haemorrhage, mechanical obstruction. Children younger than 1 year of age. Frequent and long-term administration of domperidone.
In patients with moderate or severe hepatic impairment (see Pharmacokinetics).
In patients who have known existing prolongation of cardiac conduction intervals, particularly QTc, patients with significant electrolyte disturbances or underlying cardiac diseases such as congestive heart failure.
Co-administration with QT-prolonging drugs (see Interactions).
Co-administration with potent CYP3A4 inhibitors (regardless of their QT prolonging effects) (see Interactions).
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Domperidone should be administered to Parkinsonian patients not more than 12 weeks. The possible nervous central adverse effects may happen. Domperidone should only be used in Parkinsonian patients when other safer antiemetic measures have failed. Domperidone should be administered with caution in patients with liver and kidney impairment.
Renal impairment:
The elimination half-life of domperidone is prolonged in severe renal impairment. For repeated administration, the dosing frequency of domperidone should be reduced to once or twice daily depending on the severity of the impairment. The dose may also need to be reduced.
Cardiovascular effects:
Domperidone has been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been very rare cases of QT prolongation and torsades de pointes in patients taking domperidone. These reports included patients with confounding risk factors, electrolyte abnormalities and concomitant treatment which may have been contributing factors (see Undesirable effects).
Epidemiological studies showed that domperidone was associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death (see Undesirable effects). A higher risk was observed in patients older than 60 years, patients taking daily doses greater than 30 mg, and patients concurrently taking QT-prolonging drugs or CYP3A4 inhibitors.
Domperidone should be used at the lowest effective dose in adults and children.
Domperidone is contraindicated in patients with known existing prolongation of cardiac conduction intervals, particularly QTc, in patients with significant electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia), or bradycardia, or in patient with underlying cardiac diseases such as congestive heart failure due to increased risk of ventricular arrhythmia (see Contraindications). Electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia) or bradycardia are known to be conditions increasing the proarrythmic risk.
Treatment with domperidone should be stopped if signs or symptoms occur that may be associated with cardiac arrhythmia, and the patient should consult their physician.
Patient should be advised to promptly report any cardiac symptoms.
Related to lactose excipient:
Patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
USE IN PREGNANCY AND LACTATION:
Pregnancy:
Modom’S is contraindicated in pregnant women.
Breast-feeding:
Domperidone is excreted in human milk and breast-fed infants receive less than 0.1% of the maternal weight-adjusted dose. Occurrence of adverse effects, in particular cardiac effects cannot be excluded after exposure via breast milk. A decision should be made whether to discontinue breast-feeding or to discontinue/abstain from domperidone therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the women. Caution should be exercised in case of QTc prolongation risk factor in breast-fed infants.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
Domperidone has no or negligible influence on the ability to drive or use machines.
INTERACTIONS:
The effect of domperidone is inhibited by anticholinergic agents, opioid analgesics and antimuscarinic drugs.
Increased risk of occurrence of QT-interval prolongation, due to pharmacodynamic and/or pharmacokinetic interactions.
Concomitant use of the following substances is contraindicated:
QTc-prolonging medicinal products:
– anti-arrhythmics class IA (e.g., disopyramide, hydroquinidine, quinidine)
– anti-arrhythmics class III (e.g., amiodarone, dofetilide, dronedarone, ibutilide, sotalol)
– certain antipsychotics (e.g., haloperidol, pimozide, sertindole)
– certain antidepressants (e.g., citalopram, escitalopram)
– certain antibiotics (e.g., erythromycin, levofloxacin, moxifloxacin, spiramycin)
– certain antifungal agents (e.g., pentamidine)
– certain antimalarial agents (in particular halofantrine, lumefantrine)
– certain gastro-intestinal medicines (e.g., cisapride, dolasetron, prucalopride)
– certain antihistaminics (e.g., mequitazine, mizolastine)
– certain medicines used in cancer (e.g., toremifene, vandetanib, vincamine)
– certain other medicines (e.g., bepridil, diphemanil, methadone)
(see Contraindications)
Potent CYP3A4 inhibitors (regardless of their QT prolonging effects), i.e:
– protease inhibitors
– systemic azole antifungals
– some macrolides (erythromycin, clarithromycin and telithromycin)
(see Contraindications).
Concomitant use of the following substances is not recommended:
Moderate CYP3A4 inhibitors i.e. diltiazem, verapamil and some macrolides.
(See Contraindications)
Concomitant use of the following substances requires caution in use:
Caution with bradycardia and hypokalaemia-inducing drugs, as well as with the following macrolides involved in QT-interval prolongation: azithromycin and roxithromycin (clarithromycin is contraindicated as it is a potent CYP3A4 inhibitor).
The above list of substances is representative and not exhaustive.
UNDESIRABLE EFFECTS:
Loss of libido, rash, and other allergic reactions. Galactorrhoea, menstrual disorders, dysmenorrhea, enlarged breast or breast tenderness due to elevated serum prolactin may be seen in patients with high doses of prolonged use.
Cardiac disorders:
Not known: ventricular arrhythmias, QTc prolongation, Torsade de pointes, sudden cardiac death (See Special warnings and precautions for use).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the National Center or Regional center for Drug Information and Adverse Drug Reactions Monitoring.
Please inform your doctor of all undesirable effects upon drug administration.
OVERDOSE:
In the event of overdose, measures including diuresis, gastric lavage, standard symptomatic treatment should be given immediately. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
PHARMACODYNAMIC PROPERTIES
ATC code: A03FA03
Modom’S contains domperidone which is a dopamine antagonist with anti-emetic properties. The drug has almost no effect on dopamine receptors in the brain, so it has no psychiatrical and neurological effects. Domperidone stimulates the gastrointestinal peristalsis, causes cardiospasm hypertonia and increase in expanded amplitude of post-prandial pyloric spasm.
PHARMACOKINETIC PROPERTIES:
Domperidone is absorbed from the gastrointestinal tract, with peak plasma concentrations occurring at approximately 30 minutes. Domperidone is metabolized through the liver, intestines and is excreted in feces and urine.
PRESENTATION: Box of 10 strips x 10 film coated tablets.
STORAGE CONDITIONS: Store in dry places, not exceeding 300C, protect from light.
SPECIFICATIONS: Manufacturer’s.
COMPOSITION:
Trimetazidine dihydrochloride………………………….. 20 mg
Excipients q.s …………………………………………….. 1 tablet
(Lactose, avicel, PVP K30, stearic acid, aerosil, sepifilm, HPMC, PEG 6000, talc, titanium dioxide, ponceau lake color).
DOSAGE FORM: Film coated tablets.
PRESENTATION: Box of 2 blisters x 30 film coated tablets.
PHARMACODYNAMICS:
Mechanism of action: Trimetazidine inhibits beta oxidation of fatty acids by blocking long-chain 3-ketoacyl-CoA thiolase. In an ischaemic cell, energy obtained during glucose oxidation requires less oxygen consumption than in the beta-oxidation process. Potentiation of glucose oxidation optimizes cellular energy processes, thereby maintaining proper energy metabolism during ischaemia.
Pharmacodynamic effects: In patients with ischaemic heart disease, trimetazidine acts as a metabolic agent, preserving the myocardial high-energy phosphate intracellular levels. Anti-ischemic effects are achieved without concomitant haemodynamic effects.
PHARMACOKINETICS:
Absorption is rapid, with a plasma peak time at prior 2 hrs after administration and balanced state at 24 to 36 hrs after repeating a dose and stabilizing highly during the treatment. The elimination half-life of trimetazidine is 6 hrs. Elimination of trimetazidine is principally urinary as unchanged.
INDICATIONS:
Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies.
CONTRAINDICATIONS:
– Hypersensitivity to the active ingredient or to any of the excipients listed in the composition.
– Parkinson disease, parkinsonian symptoms, tremors, restless leg syndrome, and other related movement disorders.
– Severe renal impairment (creatinine clearance < 30ml/ min).
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Trimetazidine can cause or worsen parkinsonian symptoms (tremor, akinesia, hypertonia), which should be regularly investigated, especially in elderly patients. In doubtful cases, patients should be referred to a neurologist for appropriate investigations. The occurrence of movement disorders such as parkinsonian symptoms, restless leg syndrome, tremors, gait instability should lead to definitive withdrawal of trimetazidine. These cases have a low incidence and are usually reversible after treatment discontinuation. The majority of the patients recovered within 4 months after trimetazidine withdrawal. If parkinsonian symptoms persist more than 4 months after drug discontinuation, a neurologist opinion should be sought. Falls may occur, related to gait instability or hypotension, in particular in patients taking antihypertensive treatment (see Adverse effects).
Caution should be exercised when prescribing trimetazidine to patients in whom an increased exposure is expected (see Dosage and administration):
– Patients with moderate renal impairment.
– Elderly patients older than 75 years old.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
Trimetazidine may cause dizziness and drowsiness, which may affect ability to drive and use machine.
PREGNANCY AND LACTATION:
Clinical studies have not proved the safety of trimetazidine; so, Vastec should not be administered to these subjects.
INTERACTIONS:
No drug interactions have been identified. However, concomitant administration of Vastec and other drugs should be monitored.
ADVERSE EFFECTS:
Nervous system disorders: dizziness, headache, Parkinson’s symptoms (tremors, slow and difficult movements, increased muscle tone), unsteady gait, restless leg syndrome, related movement disorders Other important, usually reversible after taking medications, Sleep disturbances (insomnia, drowsiness)
Cardiac disorders: palpitations, palpitations, extrasystoles, tachycardia
Vascular disorders: arterial hypotension, orthostatic hypotension, which can lead to irritability, dizziness, or fall, especially in patients on antihypertensive drugs, flushing
Gastrointestinal disturbances: Abdominal pain, diarrhea, indigestion, nausea and vomiting, constipation
Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, Provincial generalized pyoderma (AGEP), Angioedema Weakness
Systemic disorders and drug use: asthenia
Blood and lymphatic system disorders: Agranulocytosis, thrombocytopenia, thrombocytopenic purpura
Liver – Bile Disorders: Hepatitis
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE:
No documents have been reported.
DOSAGE & ADMINISTRATION:
The dose should be one tablet of 20 mg three times a day during meals.
Special populations:
Patients with renal impairment: In patients with moderate renal impairment (creatinine clearance [30-60] ml/ min), the recommended dose is 1 tablet of 20 mg twice daily, i.e., one in the morning and one in the evening during meals. (See more in Contraindications, Warnings and Cautions)
Elderly patients: Elderly patients may have increased trimetadizine exposure due to age-related decrease in renal function.
In patients with moderate renal impairment (creatinine clearance [30-60] ml/min), the recommended dose is 1 tablet of 20 mg twice daily in the morning and evening during meals.
Dose titration in elderly patients should be exercised with caution. (See more in Contraindications, Warnings and Cautions)
Paediatric population: The safety and efficacy of trimetazidine in children aged below 18 years have not been established. No data are available.
Or as prescribed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
This drug is for prescriptions only.
Shelf-life: 36 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer’s.
COMPOSITION:
Piracetam …………………………………. 800 mg
Excipients q.s ……………………………. 1 caplet
(Croscarmellose sodium, magnesium stearate, aerosil, sepifilm LP770).
DOSAGE FORM: Film coated caplet.
PRESENTATION: Box of 3 blisters x 10 caplets.
PHARMACODYNAMICS:
Piracetam, a cyclic derivative of gamma-aminobutyric acid acts to improve learning ability and memory due to the effect on neurotransmitters including acetylcholine, noradrenaline, and dopamine. Piracetam can alter neurotransmission and improve the metabolic environment of neurons.
Piracetam experimentally acts to resist metabolic disorders associated with ischemia by enhancing brain resistance to hypoxic state. Piracetam also enhances the mobilization and consumption of glucose without depending on oxygen supply, facilitates glucose conversion into pentose and maintains the synthesis of cerebral energy.
In addition, piracetam reduces platelet aggregation and in the conditions where there is abnormal rigidity of red blood cells, piracetam can restore the ability to deform and pass the capillaries. The drug acts to resist myoclonus.
PHARMACOKINETICS:
Piracetam is rapidly and completely absorbed after oral administration. Bioavailability of piracetam is close to 100%. Plasma maximum concentrations are achieved after 30 minutes, and at 2-8 hours in cerebrospinal fluid. The absorption of piracetam is not affected in long-term therapy. Piracetam diffuses to all tissues and crosses both blood-brain and placental barrier. Piracetam highest concentrations were in the cerebral cortex, frontal, parietal and occipital lobes, in the cerebral cortex and in the basal ganglia. The half-life is 4-5 hours in blood and 6-8 hours in cerebrospinal fluid. The half-life is increased in renal insufficiency patients. Piracetam is eliminated unchanged via kidneys.
INDICATIONS:
Treatment of symptoms associated with dizziness, headache, and severe delirium.
Improvement in symptoms in the elderly suffering from memory decline, dizziness, a lack of concentration or of alertness, behaviour disorders, personal negligence, dementia.
Treatment of acute ischemia, alcoholism, sickle cell anemia.
Supportive treatment of dyslexia in children.
Supportive treatment of myoclonus of cortical origin.
CONTRAINDICATIONS:
Hepatic impairment, severe renal impairment. Huntington’s disease.
PRECAUTIONS:
Patients with renal impairment; the elderly.
PREGNANCY AND LACTATION:
Piracetam should not be administered to pregnant women and nursing mothers.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
Piracetam does not affect the capability of driving vehicles and operating machinery.
INTERACTIONS:
Piracetam interacts with CNS stimulants, thyroid hormones, and warfarin.
ADVERSE EFFECTS:
Common: General disorders: fatigue. Gastrointestinal tract disorders: nausea, vomiting, diarrhea, abdominal pains, dyspepsia. Nervous system disorders: anxiety, irritability, headache, insomnia, drowsiness.
Rare: General disorders: dizziness. Nervous system disorders: tremor, sexual arousal.
Inform your physician about any adverse effects occur during the treatment.
OVERDOSAGE:
Piracetam is non-toxic even a very high dose. Special measures is not necessary in overdose.
DOSAGE & ADMINISTRATION:
Piracetam is used following oral administration.
Adults: 1 caplet x 3 times daily.
Or as directed by the physician.
Read the directions carefully before use.
Consult the physician for more information.
This drug is for prescriptions only.
Shelf-life: 36 months from the manufacturing date.
Storage conditions: Store in dry places, not exceeding 30oC, protect from light.
Specifications: Manufacturer’s.
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Japan-GMP is the Japanese Good Manufacturing Practice standard. In Japan, Japan-GMP has been established since 1974 and came into force in 1975, before EU-GMP (1989), and is constantly being updated to increase difficulty.
Japan-GMP is directly certified by Japan Medicines and Medical Devices Agency (PMDA). The agency is under the Ministry of Health, Labour and Welfare of Japan (MHLW).
In theory, Japan-GMP is equivalent to PIC/S-GMP of PIC/S, EU-GMP of Europe, CGMP-USA of the United States, etc. However, according to Pacific Bridge Medical (PBM), in fact, Japan-GMP often requires stricter quality control and assurance than western countries.
In December, 2020 in Can Tho, an announcement ceremony of JAPAN GMP certification for DHG Pharma’s medicine production line was held respectfully. Attending the ceremony were leaders of Can Tho City Department of Health, leaders of Mekong Delta hospitals, close customers, DHG Pharma’s leaders and employees.
