instruction

for medical use of the medicinal product

OMEPRAZOLE 20 ANANTA

 

Composition:

Active substance: omeprazole;

1 capsule*contains omeprazole (enteric granules) 20 mg;  

Inactive substances: corn starch, sucrose, sugar spheres, light magnesium carbonate, talc, sodium phosphate, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methacrylic copolymer (type A), polyethylene glycol (macrogol) 6000, anhydrous colloidal silicone dioxide, sodium hydroxide, titanium dioxide (E 171).

*the coating contains:

body: titanium dioxide (E 171), gelatine, carmoisine (E 122), tartrazine (E 102), brilliant blue FCF (E 133);

cap: titanium dioxide (E 171), gelatine, erythrosine (E 127).

Pharmaceutical form. Capsules.

Basic physical and chemical properties: hard gelatine capsules with a grey body and pink cap, the capsule contains white or almost white pellets (granules).

Pharmacotherapeutic group. Agents for treatment of peptic ulcer and gastroesophageal reflux disease. Proton-pump inhibitor. Omeprazole.

ATC code A02B C01.

Pharmacological properties.  

Pharmacodynamics.  

Omeprazole is a specific proton pump inhibitor of parietal cells. It inhibits secretion of gastric hydrochloric acid. This effect is reversible. Omeprazole is a weak base, which is accumulated and transformed into an active form in acidic environment of parietal cells, where it inhibits  Н⁺, К⁺-ATPase, thus, affecting the final stage of the gastric acid secretion.  

Inhibition of secretion is dose-dependent and does not affect either basal or stimulated acid secretion, regardless of the stimulation type. Omeprazole does not affect cholinergic and histaminergic receptors. Similar to the treatment with Н₂ blockers, treatment with omeprazole leads to reduced gastric acidity and, therefore, to a proportional elevation of gastrin levels. The increase of gastrin is reversible. During the long-term treatment, the amount of glandular cysts in the abdomen might increase. Such changes are physiological and are a result of the reduced acidity; this process is benign and reversible. Reduction of gastric acidity through the proton-pump inhibitors or other acid-inhibiting medications might lead to a growth of gastrointestinal bacteria. Thus, such treatment might lead to a risk of excessive growth of alimentary infections, caused by Salmonella, Campylobacter and Clostridium difficile in hospitalized patients.

The effect on the secretion of acid is directly proportional to the AUC concentration-time and does not depend on omeprazole blood plasma concentrations.

It has a bactericidal effect on Helicobacter pylori. Eradication of Н. pylori at concomitant administration of omeprazole and antibiotics allows to eliminate the symptoms of the illness, achieve fast healing of the affected mucosa and steady prolonged remission, and to decrease the risk of gastrointestinal haemorrhage.  

At reflux esophageal ulcer, the normalization of acid exposure in esophagus and maintenance of intestinal pH>4 for 24 hours with decreased stomach destructive force (slowing transformation of pepsinogen into pepsin) enhances the easing of symptoms and complete healing of esophageal damage (the level of the healing exceeds 90%).   It is highly effective at treatment of severe and complicated forms of erosive and ulcerative esophagitis, resistant to Н₂-blockers of histamine receptors. The long-term maintenance therapy averts the relapse of reflux esophagitis and decreases the risk of complications.  

Pharmacokinetics.

The active substance of omeprazole in the form of micropellets is in enteric coating. After the administration, the drug is rapidly and almost completely absorbed from the alimentary tract, however, its bioavailability does not exceed 50-55% (the first pass effect). Binding to blood plasma proteins (albumin and  alpha₁-acid-glycoprotein) is very high – 95%.

After single administration of 20 mg of omeprazole, the inhibition of gastric secretion is achieved within the 1^st hour, it achieves its maximum in 2 hours and lasts for approximately 24 hours, the manifestation of the effect depends on the dose. The ability of parietal cells to produce hydrochloride acid is restored during 3-5 days after the therapy is over.

Distribution

The volume of distribution in healthy volunteers is 0.3 l/kg and corresponds to such value in patients with renal insufficiency. In elderly patients and in patients with liver insufficiency, the volume of distribution might be slightly decreased. Omeprazole binding to plasma proteins is approximately 95%.

Metabolism and excretion

Omeprazole is completely metabolized by cytochrome P450. The main part of metabolism depends on the polymorphic CYP2C19, responsible for the formation of hydroxy omeprazole, the main metabolite in blood plasma. The rest depends on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulfone. Due to the high affinity of omeprazole for CYPC219, there is a possibility of competitive inhibition and metabolic interaction with other CYP2C19 substrates. However, due to the low omeprazole affinity for   CYP3A4, it does not have the ability to inhibit metabolism of other CYP3A4 substrates.

The following indicators demonstrate mainly the pharmacokinetics in patients with functional enzyme CYP2C19 in so-called fast metabolizers.

The preparation is transformed in liver and at least 6 metabolites are formed; this is characterized by almost complete absence of antisecretory activity.

It is excreted as metabolites (72-80%) mainly by the kidneys and by intestinal excretion (18-23%). The half-life is 0.5-1 hour (at normal liver function) or 3 hours (at chronic liver diseases).

The total plasma clearance is 30-40 l/hr after a single dose. Omeprazole elimination half-life is usually less than 1 hour after single, and after further peroral administration once a day. Omeprazole AUC increases after further administration. The increase is dose-dependent and provides for the AUC nonlinear dependence on the dose after further administration. Such dose and time dependence is attributed to a decrease in presystemic metabolism and systemic clearance, which, perhaps, is caused by omeprazole and/or its metabolites (e.g., sulfone) inhibition of the CYP2C19 enzyme. Omeprazole is completely excreted from blood plasma in between the administrations with no tendency to accumulation if administered once a day.   

No metabolite influence on gastric acid secretion has been found. Almost 80% of the oral omeprazole dose is excreted in the urine as metabolites, and the rest is excreted with faeces, mainly through biliary secretion.  

Slow metabolisers: approximately 3% of the European population and 15% of the Asian population have a lack of CYP2C19 enzyme and are so-called “slow metabolizers.” In such patients, metabolism of omeprazole is likely to be catalysed by CYP3A4. After further prescription of omeprazole at a dose of 20 mg once a day, the average AUC in such patients increases 5-10 times compared to patients who do not have a lack of the CYP2C19 enzyme (in rapid metabolisers).  The average peak plasma concentrations are also 3-5 times higher. However, these results have no influence on omeprazole dosage.

Patients with liver insufficiency:  disrupted omeprazole metabolism in patients with liver dysfunction leads to increase in AUC.  At single daily administration of the drug, no tendency to omeprazole accumulation has been observed.

Patients with renal insufficiency: omeprazole pharmacokinetics, including systemic bioavailability and rate of elimination in patients with renal insufficiency remains unchanged. Elderly patients: metabolism rate in elderly patients (75-79 years) is somewhat lowered. 

Clinical particulars.

Indications.

Adults

• - Treatment of duodenal ulcer;
• - prevention of duodenal ulcer relapse;
• - treatment of benign gastric ulcer;
• - prevention of benign gastric ulcer relapse;
• - in combination with appropriate antibiotics for eradication of Helicobacter pylori at peptic ulcer;
• - treatment of gastric ulcer and duodenal ulcer, attributed to the use of nonsteroidal anti-inflammatory agents (NSAIDs);
• - prevention of gastric and duodenal ulcer, connected to the use of nonsteroidal anti-inflammatory agents in patients in risk category;
• - treatment of reflux-esophagitis;
• - long-term treatment of patients with gastroesophageal reflux disease;
• - treatment of the symptoms of gastroesophageal reflux disease;
• - treatment of the Zollinger-Ellison syndrome.

Children

In children over 1 year old and with body weight over than 10 kg, omeprazole can be used at reflux esophagitis and symptomatic treatment of acid reflux and acid regurgitation at gastroesophageal reflux disease; in children over 4 years of age for treatment of duodenal ulcer caused by H. pylori under doctor’s control (see section “Routes of administration and dosage”).  

Contraindications.

Increased sensitivity to omeprazole, substituted benzimidazoles and to any of the inactive substances.

Omeprazole, like other proton pump inhibitors (PPIs), should not be used concomitantly with nelfinavir and atazanovir.

Interaction with other medicinal agents and other forms of interaction.

Effect of omeprazole on other medicinal agents’ pharmacokinetics.

Absorption. Decreased gastric acidity during the treatment with omeprazole can increase or decrease the absorption of those medicinal agents, the absorption of which depends on the stomach acid pH.

Ketoconazole, itraconazole, posakonazole, erlotynib

Just like with other drugs that inhibit gastric acidity, absorption and clinical efficacy of such medicinal agents as pozakonazole, erlotynib, ketoconazole, and itraconazole may decrease during the treatment with omeprazole. Concomitant administration of omeprazole and posakonazole and erlotynib should be avoided.

Digoxin

Concomitant treatment with omeprazole (20 mg per day) and digoxin increases digoxin bioavailability by 10%. Rare cases of toxicity caused by digoxin administration have been reported. However, high doses of omeprazole should be prescribed to elderly patients with caution. Therapeutic clinical monitoring of digoxin should be enhanced.

Clopidogrel

As a preventive measure, concomitant administration of omeprazole and clopidogrel should be avoided. At concomitant administration, the average thrombocyte aggregation is decreased by 47% (in 24 hours) and by 30% (on day 5).

Metabolism.

Omeprazole inhibits CYP2C19, main omeprazole-metabolising enzyme.

Therefore, metabolism of concomitantly administered drugs, which are also metabolized by CYP2C19, such as diazepam, phenytoin, warfarin (R-warfarin) or other vitamin K antagonists and cilostazol might slow down. 

Phenytoin blood plasma concentrations should be monitored during the first 2 weeks after the beginning of therapy with omeprazole; and in case phenytoin dose was adjusted, the monitoring and further drug dose adjustment should be carried out after the treatment with omeprazole is discontinued.

The INR monitoring is recommended in patients who administer warfarin or other vitamin K antagonists; a reduction of warfarin dose might be necessary (or of other vitamin K antagonist).

Concomitant administration of 20 mg of omeprazole per day, however, does not decrease the coagulation time in patients who administered warfarin for a long time.

There are data that administration of 40 mg of omeprazole increases С_max and AUC of cilostazol  by 18% and 26% accordingly, and of one of its active metabolites – by 29% and 69% accordingly.

Omeprazole is partly metabolized also by CYP3A4, but it does not inhibit this enzyme.

Therefore, omeprazole does not influence the metabolism of the drugs that are metabolized by CYP3A4, such as cyclosporine, lidocaine, chinidin, estradiol, erythromycin, and budesonide.

Omeprazole at doses of 20-40 mg per day does not have any significant effect on any other CYP enzymes.

Unknown mechanism.

Tacrolimus

There are data that concomitant administration of omeprazole increases the blood plasma level of tacrolimus. Enhanced monitoring of tacrolimus and of renal function (creatinine clearance) is necessary, and sometimes tacrolimus dosage should be adjusted. 

Methotrexate

There are data on increased levels of methotrexate at its concomitant administration with proton pump inhibitors. In case administration of high doses of methotrexate is necessary, temporary discontinuation of omeprazole needs to be considered.   

Atazanavir and nelfinavir

It has been reported that omeprazole interacts with some antiretroviral agents. Clinical significance and mechanism of action are not always known. The increase in the stomach acid  pH during the administration of omeprazole, might affect the absorption of antiretroviral drugs. The other action mechanism is possible due to CYP 2C19. In case some antiretroviral agents, such as atazanavir and nelfinavir are used, their blood plasma levels are decreased at concomitant administration with omeprazole. Therefore, concomitant administration of omeprazole and such agents as atazanavir and nelfinavir is contraindicated.

Saquinavir

There are data on increased plasma levels of other antiretroviral agents, such as saquinavir. There are also other antiretroviral drugs, which blood plasma levels remain unchanged at concomitant administration with omeprazole. 

Effects of other drugs on omeprazole pharmacokinetics

CYP2C19 and CYP3A4 inhibitors

Metabolism. As omeprazole is metabolized by CYP2C19 and CYP3A4, the drugs that inhibit CYP2C19, CYP3A4 or both enzymes (such as clarithromycin and voriconazole), can lead to increased levels of omeprazole in blood serum through slowing its metabolism. Concomitant administration of voriconazole can lead to a more than 2-fold increase in omeprazole exposition. As high doses of omeprazole are well-tolerated, no dose adjustment is needed during temporary concomitant use. However, the question of dose adjustment should be reconsidered for patients with severe liver insufficiency and if long-term treatment is indicated.

Inducers of CYP2C19, CYP3A4

The drugs that induce CYP2C19, CYP3A4 or both enzymes (such as rifampicin, St.John’s wort) might lead to decreased levels of omeprazole in blood serum by accelerating its metabolism.

Precautions for use.   

If Omeprazole 20 Ananta is prescribed for patients with gastric ulcer, it is necessary to exclude the possibility of malignant disease, as omeprazole might mask its symptoms and delay the diagnosis.  

The drug should be administered before meals.

Ifthereareanyalarmingsigns (forexample, significantinvoluntarybodyweightloss, periodicalrepeatedvomiting, dysphagia, vomitingbloodormelena) andincasegastriculcerispresentorsuspected, itisnecessarytoexcludethepresenceofmalignanttumours, asthetreatmentmightreducethemanifestationsofthesymptomsanddelaythediagnosis.

Concomitant administration of atazanavir and proton pump inhibitors is contraindicated. If the combination of atazanavir and proton pump inhibitors is unavoidable, thorough clinical monitoring is recommended (for example, viral load) in combination with increased dose of atazanavir to 400 mg with 100 mg of ritonavir; the dose of omeprazole should not exceed 20 mg.

Omeprazole is CYP2C19 inhibitor. At the beginning or in the end of the treatment with omeprazole, it is necessary to consider the possibility of interaction with those medicinal agents that are metabolized by CYP2C19. Interaction has been observed between clopidogrel and omeprazole. The clinical significance of this interaction has not been determined. As a preventive measure, concomitant administration of omeprazole and clopidogrel should be avoided.

In elderly patients and in patients with impaired liver and renal function, Omeprazole 20 Ananta bioavailability and elimination rate do not change.

Adjustment of omeprazole doze in elderly patients and in patients with impaired renal function is not needed. Dialysis in patients with chronic kidney disease does not affect omeprazole pharmacokinetics.

At impaired liver function, the maximum daily dose of the drug is 20 mg.

During omeprazole administration, the laboratory tests on liver function and blood plasma gastrin concentrations may give false results.

Omeprazole, like other medicinal agents that inhibit the secretion of hydrochloric acid in gastric juice, might reduce the absorption of vitamin В₁₂ (cianokobalamin) due to hypo- or achlorhydria. This should be considered in patients with cachexia or risk factors for reduction of vitamin В₁₂ absorption at long-term treatment.

Some published observational studies demonstrate that the therapy with proton pump inhibitor (PPI) might be associated with a small increase in the risk of fractures associated with osteoporosis. However, other published controlled clinical studies with omeprazole/esomeprazole (including 2 open long-term studies involving volunteers of the age of 12 and over) have not found any connection between administration of PPI and fractures caused by osteoporosis.  Despite the fact that the causal link between IPN and osteoporotic fracture have not been proved, patients at risk of progressing osteoporosis or osteoporotic fracture should be advised to undergo appropriate clinical monitoring according to the existent clinical recommendations for such state.

The drug contains sucrose (in the form of sugar granules) as one of the excipients, therefore, patients with rare hereditary forms of fructose intolerance, impaired glucose-galactose absorption or with sucrase-isomaltase deficiency, should not administer the drug.  

Treatment with proton pump inhibitors might increase the risk (medium degree) of gastrointestinal infections, such as Salmonella and Campylobacter.

Just like with any other long-term treatment, if the duration exceeds 1 year, it is necessary to control the patient’s state.

Patients must see a doctor if they had a gastrointestinal surgery or treatment of 4 weeks or longer because of the symptoms of a digestive disorder or acid reflux; if they have hepatitis or severe liver function disorders; if they are 55 or older and the symptoms are new or have changed recently.

Use during pregnancy or lactation

Pregnancy

Well-controlled epidemiological studies have shown no negative effect of omeprazole on pregnancy or on fetus’s/new-born’s health, therefore, the drug may be used during pregnancy.

Lactation

Omeprazole gets into breast milk, but its effect on a child is unknown, therefore, it is better to refrain from breastfeeding while administering omeprazole.

Effect on reaction rates while driving vehicles or operating other machinery

It is recommended to refrain from driving vehicles or performing potentially dangerous activities that require increased attention and psychomotor reactions rate, because such adverse reactions as dizziness and blurred vision are possible.

Routes of administration and dosage.

Adults’ dosage

Treatment and prevention of duodenal ulcer and benign gastric ulcer, including those associated with the administration of nonsteroidal anti-inflammatory drugs (NSAIDs)

The recommended dose for patients with duodenal ulcer is 20 mg of omeprazole once a day. In most patients, duodenal ulcer heals within 2 weeks. If after the initial course the ulcer did not heal completely, it is recommended to continue the treatment for another 2 weeks. In severe or relapsing cases, 40 mg of omeprazole per day is recommended, healing is usually achieved within 4 weeks.

For prevention of the relapse of duodenal ulcer in patients with a negative test result for H. Pylori, the recommended dose is 20 mg of omeprazole once a day. If the therapy is not efficient enough, the dose may be increased up to 40 mg. 

At the treatment of gastric ulcer, the recommended omeprazole dose is 20 mg once a day. In most patients, gastric ulcer heals during 4 weeks. If the ulcer does not heal completely after the initial course, it is recommended to prolong the treatment for another 4 weeks. In severe or relapsing cases it is recommended to administer 40 mg of omeprazole per day, healing is achieved during 8 weeks. 

For the prevention of the gastric ulcer relapse and insufficient response to the treatment, the recommended dose is 20 mg of omeprazole once a day. If necessary, the dose can be increased to 40 mg once a day.

Fortreatmentofthegastriculcersandduodenal ulcers associated with the administration of nonsteroidal anti-inflammatory drugs, the recommended dose is 20 mg of omeprazole once a day. In most patients, healing is achieved in 4 weeks. For patients who have not achieved healing after the initial course, further treatment during 4 weeks is recommended.

For the prevention of the gastric and duodenal ulcers associated with the administration of nonsteroidal anti-inflammatory drugs, in patients at increased risk (age > 60, history of gastric or duodenal ulcers, haemorrhages in the upper gastrointestinal tract), the recommended dose is 20 mg of omeprazole once a day.  

Eradication of H. Pylori at peptic ulcer

For the eradication of H. pylori at the choice of antibiotics, the individual tolerance to the drug should be considered; national, regional and local features and recommendations for treatment should be followed.

- Omeprazole 20 mg+clarithromycin 500 mg + amoxicillin 1000 mgtwiceadayduring 1 week, or

- Omeprazole 20 mg + clarithromycin 250 mg (ifnecessary 500 mg) + metronidazole 400 mg (ifnecessary 500 mg, ortinidazole 500 mg) twiceadayduring 1 week, or

- Omeprazole 40 mg once a day + amoxicillin 500 mg + metronidazole 400 mg (if necessary 500 mg or tinidazole 500 mg) 3 times a day during 1 week.

Treatment of gastroesophageal reflux disease, including reflux-esophagitis

The recommended dose is omeprazole 20 mg once a day. In most patients, healing is achieved during 4 weeks. Patients who do not achieve complete healing after the initial course are recommended to continue treatment for another 4 weeks. In patients with severe esophagitis, 40 mg of omeprazole once a day is recommended; in this case, healing is usually achieved during 8 weeks.

For long-term treatment of the patients with gastroesophageal reflux disease, the recommended dose is 10* mg of omeprazole once a day. If necessary, the dose can be increased up to 20-40 mg of omeprazole once a day.

While treating symptoms of gastroesophageal reflux disease, the recommended dose is 20 mg of omeprazole once a day. The dose should be adjusted individually. If the desired result is not achieved after 4 weeks of the treatment with omeprazole 20 mg once a day, the patient should be examined.

Treatment of Zollinger-Ellison syndrome

For patients with Zollinger-Ellison syndrome, the dose should be adjusted individually. The treatment continues until the clinical manifestations of the disease disappear. The recommended initial dose is 60 mg of omeprazole once a day. Monitoring of more than 90% of the patients with severe diseases and insufficient response to other kinds of treatment have found the efficacy of the maintenance therapy in doses of 20-120 mg once a day. The daily dose higher than 80 mg should be divided into 2 administrations.

Dosage for children

Children aged over 1 year and with body weight  ≥ 10 kg

 

Treatment of reflux-esophagitis

Symptomatic treatment of acid reflux and acid regurgitation at gastroesophageal reflux disease

Dosage recommendations:

Weight	Body weight	Dosage
≥ 1 year	10-20 kg	10* mg once a day. If necessary, the dose can be increased up to 20 mg once a day.
Children with body weight over 20 kg		20 mg once a day. If necessary, the dose can be increased up to 40 mg once a day.

Treatment of reflux-esophagitis:  the treatment duration is 4-8 weeks.

Symptomatic treatment of acid reflux and acid regurgitation at gastroesophageal reflux disease: the treatment duration is 2-4 weeks. If the desired result is not achieved after 2-4 weeks, the patient should be examined.

Children over 4 years of age and adolescents

Treatment of duodenal ulcer caused by H. pylori  

The choice of appropriate combination therapy should be made according to the official national, regional and local characteristics of the bacterial resistance. It is necessary to keep in mind the duration of the treatment (7-14 days) and relevant use of antibacterial agents.

The treatment should be controlled by a doctor.

Dosage recommendations:

Body weight	Dosage
15-30 kg	Omeprazole 10* mg + amoxicillin 25 mg/kg body weight + clarithromycin 7.5 mg/kg body weight. The drugs should be taken together 2 times a day during 1 week.
31-40 kg	Omeprazole 20 mg + amoxicillin 750 mg + clarithromycin 7.5 mg/kg body weight. The drugs should be taken together 2 times a day during 1 week.
˃ 40 kg	Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg. The drugs should be taken together 2 times a week during 1 week.

* – if the use of the 10 mg dose is necessary, the drug should be used in appropriate dosage.

Special patient groups

Renal function impairment

For patients with renal function impairment, no dose adjustment is needed (see section “Pharmacokinetics”).

Liver function impairment

For patients with liver function impairment, the daily dose of 10*-20 mg is enough (see section “Pharmacokinetics”).

Elderly patients (>65 years old)

For elderly patients, no dose adjustment is needed (see section “Pharmacokinetics”).

Route of administration

Omeprazole capsules should be administered in the morning, preferably before meals, without crushing the capsule (it should not be crushed or chewed), followed by some liquid.

For patients with difficulty in swallowing and for children who can drink and swallow semi-solid foods

The capsule may be opened and its contents swallowed, followed by half a glass of water, or mixed in a slightly acidic liquid, for example, in any fruit juice or apple sauce or in unsalted water. This mixture should be drunk immediately after it is prepared or within 30 minutes. Before the administration, the mixture should be stirred and followed by half a glass of water. Do not use milk or sparkling water.

Also, the capsules might be sucked and their contents swallowed, followed by half a glass of water. Granules with enterosoluble coating should not be chewed.

Children.

In children over 1 year old and body weight of more than 10 kg, omeprazole can be used if prescribed for treatment of reflux-esophagitis and symptomatic treatment of acid reflux and acid regurgitation at gastroesophageal reflux disease; and in children over 4 years old for treatment of duodenal ulcer caused by H. pylori under a doctor’s control.

Overdose.

There is limited data on omeprazole overdose in humans, which has not led to the development of life-threatening symptoms and not required specific therapy.

The symptoms of overdose are apathy, headache, tachycardia, nausea, vomiting, meteorism, diarrhoea, dizziness, abdominal pain, depression, confusion.  

There is no specific antidote. Omeprazole binds to blood plasma proteins which results in its poor elimination at dialysis. The treatment is symptomatic.

Adverse reactions.

Adverse reactions that might occur during the administration of omeprazole are systematised according to the types of organs. None of the adverse reactions has been classified as dose-dependent. 

Blood formation and lymphatic system disorders: leukopenia, thrombocytopenia; agranulocytosis, pancytopenia.

Immune system disorders: hypersensitivity reactions, including fever, angioneurotic oedema and anaphylactic reactions/shock.

Eating and metabolism disorders: hyponatremia, hypomagnesemia.  Severe hypomagnesemia may lead to hypocalcaemia; hypomagnesemia may also cause hypokalaemia.

Mental disorders: insomnia; anxiety, confusion, depression; aggression, hallucinations.

Nervous system disorders: headache; dizziness, paraesthesia, drowsiness; dysgeusia. 

Eyesight disorders: blurred vision.            

Hearing and balance disorders: vertigo.

Respiratory, thoracic, and mediastinal disorders: bronchospasm.

Gastrointestinal disorders: abdominal pain, constipation, diarrhoea, meteorism, nausea/vomitting; dry mouth; stomatitis, thrush, gastrointestinal candidiasis, microscopic colitis.  

Hepatobiliary system: increased levels of liver enzymes; hepatitis with or without jaundice; liver insufficiency, encyphalopathy in patients with present liver diseases.

Skin and subcutaneous tissue disorders:  dermatitis, itching, rash, urticaria; alopecia, photosensitivity; erythema multiforme, Stevens-Johnson’s syndrome, toxic epidermal necrolysis (TEN).

Musculoskeletal system, connective and bone tissue disorders: arthralgia, myalgia, muscular weakness.   

Urinary system disorders: interstitial nephritis.

Reproductive system and breast disorders: gynecomastia.

General disorders: malaise, peripheral oedema; excessive sweating.

The drug contains carmoisine (E 122), which may cause development of allergic reactions.

Storage life. 3 years.

Storage conditions.

Keep in the original package at a temperature not exceeding 30 °С.

Keep out of reach of children.

Package. 10  capsules in a blister, 10 blisters in a package.  

Terms of dispensing. On prescription.

Manufacturer.

Flamingo Pharmaceuticals Ltd.

Manufacturer’s registered address.

Е-28, Opp. Fire Brigade, MIDC, Taloja, Raigad district, Maharashtra,  410 208, India.

Applicant.

Flamingo Pharmaceuticals Ltd.

Applicant’s registered address.

7/1, CorporatePark, SionTrombayRoad, Chembur, Mumbai, 400071, India

Date of last review. 31.01.17.