Quamatel

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KAMATEL® (QUAMATEL®)

Composition:

Active substance: famotidine;

1 vial contains 20 mg famotidine;

1 ampoule of solvent contains 5 ml of 0.9% sodium chloride solution;

Excipients: aspartic acid, mannitol (E 421).

Pharmaceutical form. Lyophilisate for solution for injection.

Main physico-chemical properties: white or almost white lyophilisate; solvent – colorless, odorless solution.

Pharmacotherapeutic group. Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. H₂-receptor antagonists.

ATC code A02B A03.

Pharmacological Properties

Pharmacodynamics

Famotidine is a potent competitive H2-histamine receptor antagonist. The main clinically significant pharmacological action of famotidine is the inhibition of gastric secretion. Famotidine reduces both the concentration of acid and the volume of gastric secretion, while pepsin production remains proportional to the volume of gastric juice secreted.

In healthy volunteers and patients with hypersecretion, famotidine inhibits basal and nocturnal gastric secretion, as well as secretion stimulated by pentagastrin, betazole, caffeine, insulin, and the physiological vagal reflex.

The duration of inhibition following doses of 20 mg and 40 mg lasts from 10 to 12 hours.

Single oral administration of 20 mg and 40 mg doses in the evening provides inhibition of basal and nocturnal acid secretion.

Famotidine has almost no effect on fasting serum gastrin levels or postprandial gastrin levels.

Famotidine does not affect gastric emptying, exocrine pancreatic function, hepatic blood flow, or portal circulation.

Famotidine also does not affect the hepatic cytochrome P450 enzyme system.

Antiandrogenic effects of the drug have not been observed. Serum hormone levels remain unchanged after treatment with famotidine.

Pharmacokinetics

The kinetics of famotidine are linear.

Distribution: Plasma protein binding is relatively weak – 15–20%.

Half-life: 2.3–3.5 hours. In patients with severe renal impairment, the half-life of famotidine may exceed 20 hours (see section "Dosage and Administration").

Metabolism: The drug is metabolized in the liver. The only metabolite identified in humans is the sulfoxide.

Elimination: Famotidine is excreted by the kidneys (65–70%), with 30–35% of the administered dose undergoing metabolism. Renal clearance ranges from 250 to 450 mL/min, indicating some degree of tubular secretion. 65–70% of an intravenously administered dose is recovered unchanged in the urine. A small amount of the administered dose may be excreted as the sulfoxide metabolite.

Clinical characteristics.

Indications.

• Benign gastric ulcer.
• Duodenal peptic ulcer.
• Conditions of hypersecretion, such as Zollinger-Ellison syndrome.
• Treatment of gastroesophageal reflux disease.
• Prevention of aspiration of acidic gastric contents (Mendelson's syndrome) during general anesthesia.

Contraindications.

Hypersensitivity to the active substance, to any of the excipients, or to other H2-histamine receptor antagonists.

Paediatric age; pregnancy or lactation period (due to lack of sufficient clinical experience).

Interaction with other medicinal products and other forms of interactions.

The absorption of certain medicinal products (e.g., ketoconazole, amoxicillin, iron preparations) depends on gastric acidity. Therefore, famotidine should be administered at least 2 hours after such medicinal products.

Concomitant use with other H2-receptor antagonists may significantly reduce the effectiveness of tolazoline. Although there are no confirmed interactions between famotidine and tolazoline, the likelihood of such interactions is sufficiently high; therefore, the effect of tolazoline should be monitored at the beginning and after completion of concomitant therapy. If the effect of tolazoline is reduced, its dose should be gradually increased or famotidine treatment discontinued.

Food and antacids do not significantly affect famotidine treatment.

There is a risk of reduced efficacy of calcium carbonate used for phosphate binding in hemodialysis patients when administered concomitantly with famotidine.

Famotidine does not affect the hepatic cytochrome P450 oxidase system; therefore, the metabolism of oral anticoagulants, antipyrine, aminopyrine, theophylline, phenytoin, diazepam, ethanol, and propranolol remains unchanged.

Probenecid may delay the elimination of famotidine.

Concomitant use of posaconazole oral suspension and famotidine should be avoided if possible, as famotidine may reduce the absorption of posaconazole oral suspension when administered simultaneously.

Concomitant use of famotidine with tyrosine kinase inhibitors (TKIs), such as dasatinib, erlotinib, gefitinib, pazopanib, may lead to decreased plasma concentrations of TKIs and, consequently, reduced efficacy. Therefore, concomitant use of famotidine with these TKIs is not recommended. For further additional recommendations, please refer to the prescribing information of individual medicinal products containing TKIs.

Special precautions for use.

Before starting treatment with the medicine Quamatel®, it is necessary to exclude the presence of malignant tumors in the stomach and duodenum. Treatment with this drug may mask the symptoms of gastric carcinoma.

In patients with hepatic insufficiency, Quamatel® should be used with caution and in low doses.

Since cross-sensitivity between H2-receptor antagonists has been reported, the use of Quamatel® is contraindicated in patients with known hypersensitivity to other H2-receptor antagonists.

Treatment with Quamatel® must not be initiated without a physician's prescription or proper medical evaluation if:

• the patient suffers from kidney or liver disease. In elderly patients or patients with impaired liver or kidney function, psychiatric disorders (confusion) may occur, requiring dose reduction;
• the patient has concomitant diseases or is taking other medicinal products simultaneously;
• the patient of middle or advanced age experiences new-onset digestive complaints or changes in previous symptoms;
• the patient has gastric complaints accompanied by weight loss;
• black-colored stools appear;
• the patient has swallowing difficulties or chronic abdominal pain.

The drug should be used with caution in cases of acute porphyria (including in the medical history) and immunodeficiency.

Symptoms of duodenal ulcer may disappear within 1–2 weeks, but treatment should be continued until healing is confirmed by endoscopic or X-ray examination.

Regular monitoring of patients (especially elderly patients and those with a history of gastric and/or duodenal ulcer) who are taking this drug in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) is required.

When used concomitantly with antacids, the interval between administration of the drug and antacids should be at least 1–2 hours.

If a dose is missed, it should be taken as soon as possible; the dose should not be doubled if it is time for the next scheduled dose.

Treatment with this drug should not be initiated without prior proper medical evaluation in elderly patients presenting with heartburn, symptoms of hyperacidity, stomach pain, or hyperacidity after food intake.

This medicinal product contains 18 mg of sodium per dose (5 ml of solvent contains 0.9% sodium chloride), which is equivalent to 0.9% of the WHO recommended maximum daily intake of sodium for an adult (2 g). The medicine contains less than 1 mmol of sodium (23 mg) per 5 ml dose, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

Fertility

In studies conducted in rats and rabbits, oral administration of famotidine at doses up to 2000 and 500 mg/kg body weight per day, respectively, did not reveal any impairment of reproductive function. However, adequate and well-controlled studies in pregnant women have not been conducted.

Pregnancy

Pregnancy safety category B.

Famotidine crosses the placenta. Reliable and well-controlled human studies have not been conducted.

The use of Quamatel® during pregnancy is contraindicated (see section "Contraindications").

Breastfeeding period

Famotidine is excreted in human breast milk; therefore, breastfeeding should be discontinued during treatment with Quamatel®.

The use of Quamatel® during breastfeeding is contraindicated (see section "Contraindications").

Ability to affect reaction speed when driving or operating machinery.

Patients should exercise caution when performing potentially hazardous activities requiring increased attention and rapid psychomotor reactions, as this drug may cause dizziness.

Method of Administration and Dosage

Dosage

Quamatel®, lyophilisate for solution for injection, can be administered only in a hospital setting and only to patients who cannot take the drug orally. As soon as possible, patients should be switched to oral administration of Quamatel® tablets.

The usual dose of Quamatel®, lyophilisate for solution for injection, is 20 mg twice daily (every 12 hours).

Zollinger-Ellison Syndrome

The initial dose is 20 mg (every 6 hours) and may be increased depending on gastric acid secretion and the patient's clinical condition.

Prevention of gastric fluid aspiration during general anesthesia

20 mg intravenously in the morning on the day of surgery or at least 2 hours before the start of surgery.

The single dose for intravenous administration must not exceed 20 mg.

Renal Impairment

Since famotidine is primarily excreted by the kidneys, Quamatel® should be used with caution in patients with severe renal impairment.

If creatinine clearance is < 30 mL/min and serum creatinine concentration is > 3 mg/100 mL, the daily dose should be reduced to 20 mg or the dosing interval should be extended to 36–48 hours.

Cardiovascular Diseases

Prolonged intravenous infusion is recommended.

Use in Pediatric Practice

The safety and efficacy of the drug in children have not been established. The use of Quamatel®, lyophilisate for solution for injection, in children and adolescents is contraindicated (see section "Contraindications").

Elderly Patients

There is no need to adjust the dosage based on age.

Method of Administration

Quamatel®, lyophilisate for solution for injection, is intended for intravenous administration only.

For intravenous injection, the contents of the vial should be dissolved in 5–10 mL of 0.9% sodium chloride solution (solvent ampoule). The reconstituted solution is stable for 24 hours at room temperature. The diluted solution should be administered slowly over 2 minutes.

When administered as an intravenous infusion, the solution should be infused over 15–30 minutes. According to compatibility studies, the following infusion solutions may be used:

The solution of the drug must be prepared immediately before use. Only a clear, colorless solution may be used.

Children.

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

Overdose.

When famotidine was administered at a dose of 800 mg per day for one year in patients with pathological hypersecretion syndrome, no severe adverse effects were observed.

Treatment: symptomatic and supportive therapy, monitoring of the patient's condition.

Adverse reactions.

The following adverse events have been reported as isolated or rare. However, in many cases, a causal relationship to famotidine therapy has not been established.

* Gynecomastia occurs very rarely and is reversible after discontinuation of treatment.

Reporting of suspected adverse reactions

Reporting of suspected adverse drug reactions occurring after the registration of the medicinal product is very important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions through the national reporting systems.

Shelf life.

2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging to protect from light. Keep out of reach and sight of children.

Packaging.

5 vials of lyophilisate for solution for injection with 5 ampoules of solvent in a cardboard pack.

Prescription category.

Prescription only.

Manufacturer.

JSC "Gedeon Richter", Hungary.

Manufacturer's address and location of operation.

H-1103 Budapest, Dózsa György út 19-21, Hungary.