Quamatel^® (Tablets, Lyophilisate) Instructions for Use

ATC Code

A02BA03 (Famotidine)

Active Substance

Famotidine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Histamine H₂-receptor blocker. Antiulcer drug

Pharmacotherapeutic Group

Acid-related disorder treatment agents; antiulcer agents and agents for the treatment of gastroesophageal reflux disease (GERD); histamine H₂-receptor blockers

Pharmacological Action

Famotidine is a potent competitive inhibitor of histamine H₂-receptors.

The main clinically significant pharmacological action of famotidine is the inhibition of gastric secretion. Famotidine reduces both the concentration of hydrochloric acid and the volume of gastric secretion, while changes in pepsin secretion occur proportionally to the secreted volume.

In healthy volunteers and patients with increased gastric secretion, Famotidine inhibits basal and nocturnal secretion of hydrochloric acid, as well as secretion stimulated by the administration of pentagastrin, betazole, caffeine, insulin, and the physiological vagus nerve reflex.

The duration of secretion inhibition with a dose of 20 mg and 40 mg is 10-12 hours. A single evening oral dose of 20 mg and 40 mg suppresses basal and nocturnal acid secretion. Nocturnal gastric secretion is inhibited by 86-94% for at least 10 hours. Application of the drug in the same dose in the morning suppresses acid secretion stimulated by food intake; the degree of inhibition is 76-84% for 3-5 hours and 25-30% for 8-10 hours after application.

Famotidine does not affect the serum gastrin concentration on an empty stomach or after a meal. Famotidine does not affect gastric emptying, exocrine function of the pancreas, liver and portal system blood flow.

Famotidine does not affect the activity of cytochrome P450 isoenzymes.

No antiandrogenic effect was noted in clinical pharmacological studies. Serum hormone concentrations did not change after famotidine administration.

Pharmacokinetics

The kinetics of famotidine are linear.

Absorption

Famotidine is rapidly absorbed.

After oral administration, C_max of famotidine in blood plasma is reached in 1-3 hours. Bioavailability with oral use is 40-45%. Bioavailability does not depend on food intake, but is somewhat reduced with the use of antacids; this effect has no clinical significance. Presystemic metabolism of famotidine has only a minor effect on bioavailability.

Distribution

No cumulative effect occurs with repeated administration.

Binding to plasma proteins is relatively low: 15-20%.

Metabolism

Famotidine is metabolized in the liver.

The only metabolite identified in humans is the sulfoxide.

Excretion

T_1/2 from blood plasma: 2.3-3.5 hours.

In patients with severe renal failure, the terminal T_1/2 of famotidine may exceed 20 hours.

Famotidine is excreted by the kidneys (65-70%) and by metabolism (30-35%). Renal clearance is 250-450 ml/min, indicating some degree of tubular excretion. 25-30% of the drug when taken orally and 65-70% of the drug when administered intravenously is found in the urine unchanged. A small amount may be excreted as sulfoxide.

Linearity

The kinetics of famotidine are linear.

Special patient groups

In elderly patients (over 65 years old) no clinically significant changes in famotidine bioavailability associated with age were noted.

Indications

Adults over 18 years old

• Duodenal and gastric ulcer without malignancy in the acute phase, prevention of relapse;
• Gastroesophageal reflux disease;
• Other conditions accompanied by hypersecretion (for example, Zollinger-Ellison syndrome);
• Prevention of gastric juice aspiration during general anesthesia (Mendelson’s syndrome).

ICD codes

Dosage Regimen

Lyophilisate

For duodenal ulcer, gastric ulcer without malignancy, gastroesophageal reflux disease: the recommended dose is 20 mg IV 2 times/day (every 12 hours).

For Zollinger-Ellison syndrome: the initial dose is 20 mg IV every 6 hours, then – the dose of the drug depends on the volume of secretion and the clinical condition of the patient.

For general anesthesia to prevent aspiration of acidic gastric contents: Quamatel^® is used at a dose of 20 mg IV in the morning on the day of surgery or at least 2 hours before the start of surgery.

A single dose for IV administration cannot exceed 20 mg.

Special groups of patients

Patients with impaired renal function. Since Famotidine is excreted primarily by the kidneys, caution must be exercised in patients with severe renal failure. If creatinine clearance is less than 30 ml/min, and serum creatinine concentration exceeds 3 mg/100 ml, then the daily dose must be reduced to 20 mg or the interval between administrations increased to 36-48 hours.

Patients with impaired liver function. In hepatic insufficiency, the drug Quamatel^® should be prescribed with caution at a reduced dose.

Dose adjustment in elderly patients is not required.

Children and adolescents under 18 years of age. The safety and efficacy of the drug in children and adolescents under 18 years of age have not been established. The use of the drug Quamatel^® is contraindicated in this category of patients.

Method of administration

The drug Quamatel^® lyophilisate for the preparation of solution for IV administration is intended for IV administration only.

For IV injection the prepared solution should be administered slowly (over at least 2 minutes).

For IV infusion the duration of infusion should be 15-30 minutes.

Solutions should be prepared immediately before administration.

Preparation of solutions

To perform an IV injection, the contents of the vial should be dissolved in 5-10 ml of 0.9% sodium chloride solution (ampoule of solvent).

The following solutions are recommended for dilution

• 5% glucose solution;
• Ringer’s solution;
• Ringer’s lactate solution;
• 0.9% sodium chloride solution.

Only clear, colorless solutions can be used.

Tablets

The drug is taken orally, regardless of food intake.

The tablets should be swallowed whole, without chewing, with a glass of water.

Exacerbation of gastric and duodenal ulcer

The drug is taken at 40 mg once/day at bedtime or 20 mg 2 times/day (morning and evening). The duration of treatment is 4-8 weeks. The duration of treatment may be shorter if endoscopic examination reveals early ulcer healing. In most patients, healing is noted within 4 weeks. In patients who do not show complete recovery after 4 weeks, it is recommended to continue treatment for an additional 4 weeks.

Gastric ulcer without malignancy

The recommended dose is 40 mg once/day at bedtime. Treatment should be continued for 4-8 weeks. The duration of treatment may be shorter if endoscopic examination reveals early ulcer healing.

Prevention of ulcer exacerbation

The drug is prescribed at 20 mg once/day at bedtime.

Gastroesophageal reflux disease

The drug is taken at 20 mg 2 times/day (morning and evening) for 6-12 weeks. If gastroesophageal reflux disease is accompanied by esophagitis, the recommended dose of the drug Quamatel^® is 20-40 mg/day for 12 weeks.

Zollinger-Ellison syndrome

In patients who have not previously taken drugs to reduce gastric secretion, the initial dose is usually 20 mg every 6 hours. Then the dose should be selected individually depending on the patient’s condition.

Patients who are using other H₂-histamine receptor blockers can immediately switch to using the drug Quamatel^® at a dose exceeding the recommended initial dose of 20 mg every 6 hours.

The duration of drug use depends on the clinical condition of the patient.

Prevention of gastric juice aspiration during general anesthesia (Mendelson’s syndrome)

The drug is taken at a dose of 40 mg in the evening before surgery or in the morning on the day of surgery.

Special groups of patients

Since Famotidine is excreted primarily by the kidneys, caution must be exercised in patients with severe renal failure. If creatinine clearance <30 ml/min or serum creatinine >3 mg/100 ml, the daily dose must be reduced to 20 mg or the interval between doses increased to 36-48 hours.

Elderly patients (over 65 years old) do not require a dose change.

The efficacy and safety of the drug when used in children and adolescents under 18 years of age have not been established.

Adverse Reactions

Adverse reactions are presented according to the frequency of occurrence: very common (≥1/10); common (from ≥1/100 to <1/10); uncommon (from ≥1/1000 to <1/100); rare (from ≥1/10,000 to <1/1,000); very rare (<1/10,000), frequency unknown (cannot be estimated from available data). In each frequency group, adverse reactions are presented in order of decreasing severity.

*Rare cases of gynecomastia have been reported, but in controlled clinical studies their frequency did not exceed that in the placebo group. The effect disappears when treatment is stopped.

Contraindications

• Hypersensitivity to famotidine and other histamine H₂-receptor blockers;
• Hypersensitivity to any of the excipients of the drug;
• Rare hereditary galactose intolerance, lactose intolerance or glucose-galactose malabsorption.

With caution

In hepatic insufficiency or with a history of liver cirrhosis with portosystemic encephalopathy, the drug Quamatel^® should be used with caution and at lower doses.

Since Famotidine is excreted primarily by the kidneys, the drug should be used with caution in renal failure. If creatinine clearance falls below 10 ml/min, a reduction in the daily dose of the drug is recommended.

Use in Pregnancy and Lactation

Pregnancy

In preclinical studies, Famotidine crossed the placental barrier.

Adequate or well-controlled studies in pregnant women have not been conducted. The drug should be prescribed during pregnancy only if there are clear clinical indications. Before deciding to use the drug Quamatel^® during pregnancy, the doctor should assess the potential benefit of taking the drug relative to the possible risk.

Breastfeeding period

Famotidine passes into breast milk.

The effect of famotidine on breastfed infants is unknown. Famotidine may affect the secretory function of the child’s stomach, so nursing mothers should stop using the drug or stop breastfeeding.

Fertility

Adequate or well-controlled studies have not been conducted.

Use in Hepatic Impairment

The drug should be prescribed with caution in hepatic insufficiency, liver cirrhosis with a history of portosystemic encephalopathy.

Use in Renal Impairment

The drug should be prescribed with caution in renal failure.

Pediatric Use

The efficacy and safety of the drug when used in children and adolescents under 18 years of age have not been established.

Geriatric Use

Elderly patients (over 65 years old) do not require a dose change.

Special Precautions

If swallowing difficulties occur or abdominal discomfort persists, the patient should consult a doctor.

Gastric neoplasm

Before starting treatment of gastric ulcer with the drug Quamatel^®, it is necessary to exclude the presence of malignant gastric neoplasms.

Symptomatic response of a gastric ulcer to therapy does not exclude the presence of a malignant neoplasm.

Use in pediatrics

The safety and efficacy of the drug when used in children and adolescents have not been established.

Elderly patients (over 65 years old)

Clinical studies have not shown an increase in the frequency or change in the type of side effects in elderly patients associated with the use of famotidine.

Dose adjustment depending on age is not required.

General instructions

In case of long-term use of the drug at a high dose, regular complete blood count and assessment of liver function are recommended.

In chronic peptic ulcer disease, the drug should not be abruptly discontinued after the symptoms have subsided.

Excipients

In case of lactose intolerance, it should be taken into account that each tablet of the drug Quamatel^® 20 mg contains 105 mg of lactose monohydrate, and each tablet of the drug Quamatel^® 40 mg contains 90 mg of lactose monohydrate.

Patients with lactose intolerance, lactase deficiency or glucose-galactose malabsorption should not use the drug Quamatel^®.

Effect on ability to drive vehicles and mechanisms

The potential for the development of such side effects as dizziness and headache should be taken into account.

If such symptoms develop, patients should not drive vehicles, operate machinery, or engage in activities requiring increased concentration.

Overdose

Adverse reactions in case of overdose are similar to those observed in normal clinical practice.

Treatment gastric lavage, symptomatic and supportive therapy; clinical observation.

Drug Interactions

No clinically significant drug interactions have been identified.

When using the drug Quamatel^®, film-coated tablets, simultaneously with drugs whose absorption depends on the acidity of gastric juice, the change in the absorption of such drugs should be taken into account.

All drugs that inhibit gastric juice secretion can affect the bioavailability and rate of absorption of certain drugs, leading to reduced absorption of atazanavir due to changes in gastric pH.

Due to an increase in gastric pH with simultaneous use with famotidine, the absorption of ketoconazole and itraconazole may decrease. Therefore, ketoconazole should be taken no later than 2 hours before taking the drug Quamatel^®.

The absorption of the drug Quamatel^® may be reduced with simultaneous use with drugs that neutralize the acidity of gastric juice (antacids), which may lead to a decrease in the plasma concentration of famotidine. Therefore, antacids should be taken 1-2 hours after taking the drug Quamatel^®.

The use of sucralfate should be avoided within 2 hours before or after taking famotidine.

The administration of probenecid may reduce the elimination rate of famotidine, therefore its simultaneous use with Quamatel^® should be avoided.

Famotidine does not affect the activity of cytochrome P450 isoenzymes.

Clinical studies have shown that Famotidine does not enhance the effect of amidopyrine, antipyrine, diazepam, phenytoin, propranolol, theophylline, and warfarin. In a test with indocyanine green, used as an indicator of hepatic blood flow and/or hepatic drug extraction, no significant effects were identified.

Studies involving patients whose condition was adequately controlled with phenprocoumon showed no pharmacokinetic interaction with famotidine and no effect of famotidine on the pharmacokinetics and anticoagulant activity of phenprocoumon.

According to research, Famotidine does not affect the degree of ethanol absorption into the blood when consuming alcohol.

Storage Conditions

The drug should be stored out of the reach of children, in a light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 5 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.