Quamatel®

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

Composition:

Active substance: famotidine;

One film-coated tablet contains 20 mg or 40 mg of famotidine, respectively;

Excipients: colloidal anhydrous silicon dioxide, magnesium stearate, povidone K 90, sodium starch glycolate (type A), talc, maize starch, lactose monohydrate; coating: iron oxide red (E 172), colloidal anhydrous silicon dioxide, titanium dioxide (E 171), macrogol 6000, seppifilm 003 (composition: macrogol-40 (E 431)), microcrystalline cellulose (E 460), hypromellose (E 464)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

Kamatel®, 20 mg tablets: pink, convex film-coated tablets with marking "F 20" on one side. Tablet diameter – approximately 8 mm.

Kamatel®, 40 mg tablets: dark pink, convex film-coated tablets with marking "F 40" on one side. Tablet diameter – approximately 8 mm.

Pharmacotherapeutic group.

Agents for treatment of acid-related disorders. H2-receptor antagonists.

ATC code A02BA03.

Pharmacological properties.

Pharmacodynamics.

Famotidine is a potent competitive H2-histamine receptor antagonist. The main clinically significant pharmacological effect of famotidine is 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 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 of secretion after administration of 20 mg and 40 mg doses lasts from 10 to 12 hours. A single oral dose of 20 mg or 40 mg taken in the evening provides inhibition of basal and nocturnal acid secretion. Nocturnal hydrochloric acid secretion is inhibited by 86–94% for at least 10 hours. The same doses taken in the morning reduce food-stimulated acid secretion. This suppression amounts to 76–84% of initial secretion 3–5 hours after administration and 25–30% 8–10 hours after administration, respectively.

Famotidine has almost no effect on fasting or postprandial serum gastrin levels. Famotidine does not affect gastric emptying, exocrine pancreatic function, hepatic blood flow, or portal system circulation.

Famotidine does not influence the hepatic cytochrome P-450 enzyme system.

No antiandrogenic effects of the drug have been observed. Serum hormone levels remain unchanged after treatment with famotidine.

Pharmacokinetics.

The kinetics of famotidine are linear.

Absorption. Famotidine is rapidly absorbed. Oral bioavailability is 40–45%. Bioavailability is not affected by the presence of food in the stomach, although it is slightly reduced when antacids are co-administered.

Clinically significant age-related changes in the bioavailability of famotidine have not been observed in elderly patients.

First-pass metabolism in the liver has a minimal effect on the drug's bioavailability.

Distribution. After oral administration, peak plasma concentrations are reached within 1–3 hours. With repeated dosing, no cumulative effect occurs. Plasma protein binding is relatively low, at 15–20%.

Elimination half-life – 2.3–3.5 hours. In patients with severe renal impairment, the elimination half-life of famotidine may exceed 20 hours.

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

Excretion. Famotidine is excreted by the kidneys (65–70%) and via metabolism (30–35% of the administered dose). Renal clearance ranges from 250 to 450 mL/min, indicating some degree of tubular excretion. 25–30% of an orally administered dose and 65–70% of an intravenously administered dose are recovered unchanged in the urine. A small portion of the administered dose may be excreted as the sulfoxide metabolite.

Clinical characteristics.

Indications.

• Benign gastric ulcer.
• Duodenal peptic ulcer (treatment and prevention of recurrences).
• Conditions of hypersecretion, such as Zollinger−Ellison syndrome.
• Treatment of gastroesophageal reflux disease (reflux esophagitis).
• Prevention of development of symptoms and erosions or ulceration associated with gastroesophageal reflux disease.

Contraindications.

Hypersensitivity to any component of the medicinal product.

Cross-sensitivity has been observed among drugs of this class. Therefore, Kvamatel® should not be administered to patients with a history of hypersensitivity to other H2-receptor blockers.

Interaction with other medicinal products and other forms of interaction.

No clinically significant drug interactions have been identified.

When Kvamatel®, film-coated tablets, are used concomitantly with medicinal products whose absorption depends on gastric acidity, altered absorption of such medicinal products should be considered.

All medicinal products that inhibit gastric juice secretion may alter the bioavailability and rate of absorption of certain drugs, leading to reduced absorption of atazanavir due to changes in gastric pH. Due to increased gastric pH, famotidine may reduce the absorption of ketoconazole and itraconazole when used concomitantly. Therefore, ketoconazole should be taken at least 2 hours before administration of Kvamatel® tablets.

Absorption of Kvamatel® tablets may be reduced when used with medicinal products that counteract or neutralize gastric acidity (antacids), which may result in decreased plasma concentration of famotidine. Therefore, antacids should be taken 1–2 hours after administration of Kvamatel® tablets.

Concomitant use of sucralfate within two hours before or after famotidine administration should be avoided.

Administration of probenecid may delay elimination of famotidine; therefore, concomitant use of Kvamatel® tablets and probenecid should be avoided.

Famotidine does not affect the activity of hepatic metabolism enzymes of the cytochrome P-450 group.

Clinical studies have shown that famotidine does not potentiate the effects of aminopyrine, antipyrine, diazepam, phenytoin, propranolol, theophylline, and warfarin.

In the indocyanine green test as an indicator of hepatic blood flow and/or hepatic extraction of the drug, no significant effect was observed.

Studies in patients receiving concomitant therapy with phenprocoumon showed no pharmacokinetic interaction with famotidine and no effect on the anticoagulant activity of phenprocoumon.

Furthermore, studies with famotidine have not shown an increase in expected blood alcohol levels following alcohol consumption.

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

Concomitant administration of posaconazole oral suspension and famotidine should be avoided if possible, since famotidine may reduce absorption of posaconazole oral suspension when used concomitantly.

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

Special precautions for use.

In case of hepatic insufficiency, Quamatel® should be used with caution and in lower doses.

If patients experience difficulty swallowing or persistent abdominal discomfort, they should consult a physician.

Malignant gastric tumors

Before initiating treatment of gastric ulcer with Quamatel®, the presence of malignant gastric tumors must be ruled out. Symptom relief of gastric ulcer due to Quamatel® therapy does not exclude the presence of gastric malignancies.

Renal insufficiency

Since famotidine is primarily excreted via the kidneys, it should be used with caution in patients with impaired renal function. When creatinine clearance decreases below 10 mL/min, a reduction in the daily dose is recommended (see section "Dosage and administration").

Children

The efficacy and safety of the drug in children have not been established. The use of Quamatel® film-coated tablets in children and adolescents is not recommended.

Geriatric patients

During clinical trials, no differences in the frequency or types of adverse reactions were observed in elderly patients treated with famotidine compared to the general adult population. Advanced age alone does not require dose adjustment.

General considerations

With prolonged use of high doses of the drug, regular monitoring of complete blood count and liver function is recommended.

In chronic peptic ulcer disease, abrupt discontinuation of the drug after symptom relief is not recommended.

Quamatel® contains lactose.

In patients with lactose intolerance, it should be noted that one 20 mg film-coated tablet of Quamatel® contains 105 mg of lactose, and one 40 mg film-coated tablet contains 90 mg of lactose. This medicinal product should not be administered to patients with rare hereditary conditions such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Fertility

Controlled studies in pregnant women have not been conducted.

Pregnancy.

Animal studies have shown that famotidine crosses the placenta. Controlled studies in pregnant women to confirm this have not been conducted. Quamatel® is not recommended during pregnancy. The drug may be prescribed to pregnant women only if there are substantial clinical indications. Before deciding to use Quamatel®, the physician should evaluate the potential benefits of treatment against possible risks.

Breastfeeding period. Famotidine passes into human breast milk. Since the effects of famotidine on breastfed infants are unknown and it may possibly impair gastric secretory function in the infant, women who are breastfeeding should either discontinue the drug or stop breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Some patients experienced dizziness and headache while taking famotidine. Patients should be advised to avoid driving, operating machinery, or performing tasks requiring heightened attention if these symptoms occur (see section "Adverse reactions").

Dosage and Administration

The drug demonstrates the highest efficacy when administered in the evening before bedtime. When famotidine is used twice daily, one dose should be taken in the morning and the other in the evening before bedtime. Swallow the Quamatel® tablet whole, without chewing, with a glass of water, regardless of food intake.

Benign gastric and duodenal ulcer

The recommended dose is 40 mg once daily at bedtime. Treatment duration –
4-8 weeks.

Prevention of duodenal ulcer relapse

For prevention of relapse after achieving therapeutic effect, a maintenance dose of 1 tablet 20 mg once daily at bedtime is used. Treatment duration –
1-4 weeks.

Gastroesophageal reflux disease (GERD)

1 tablet of 20 mg or 40 mg (depending on disease severity) twice daily (1 tablet in the morning and 1 in the evening) for 6-12 weeks.

If gastroesophageal reflux disease is associated with erosive esophagitis or ulceration, the recommended dose of Quamatel® is 40 mg twice daily for 6-12 weeks.

Prevention of symptoms and development of erosions or ulceration associated with gastroesophageal reflux disease (maintenance therapy)

The recommended dose is 20 mg twice daily.

Zollinger-Ellison syndrome

The initial dose is usually 20 mg every 6 hours in patients who have not previously received antisecretory therapy. The dose should then be adjusted according to the patient's condition.

Patients previously treated with another H2-antihistamine agent may switch to Quamatel® using a higher initial dose – 40 mg every 6 hours. The dose should be adjusted based on gastric juice secretion levels and the patient's clinical condition. Treatment should continue as long as clinically indicated. The daily dose may be increased as needed, depending on individual patient characteristics, to achieve the optimal dose. According to published data, maximum doses of famotidine used in patients with severe forms of the disease reached up to 160 mg every 6 hours.

Renal impairment

Since famotidine is primarily excreted by the kidneys, it should be used with caution in patients with impaired renal function.

If creatinine clearance is <30 mL/min and serum creatinine level 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.

Use in elderly patients

Dose adjustment based on age is not required.

Children.

The efficacy and safety of the drug in children have not been established. The use of Quamatel® film-coated tablets in children and adolescents is not recommended.

Overdose.

Adverse reactions in overdose are similar to those observed in usual clinical practice (see section "Adverse Reactions"). Patients with Zollinger-Ellison syndrome have tolerated daily oral doses of famotidine up to 800 mg for more than 1 year without development of serious adverse effects.

Treatment in case of overdose

Following ingestion of a high dose of the drug, gastric lavage, symptomatic and supportive therapy, and clinical monitoring are required.

Adverse reactions.

Famotidine is generally well tolerated.

The adverse reactions listed below have been reported very rarely or rarely. However, in many cases, a causal relationship to famotidine administration has not been established.

* Rare cases of gynecomastia have been reported; however, in controlled clinical trials, the incidence was not higher than with placebo. The effect is reversible upon discontinuation of treatment.

After marketing authorization, it is important to report suspected adverse reactions. This enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

Shelf life.

Quamatel®, film-coated tablets, 20 mg:

4 years.

Quamatel®, film-coated tablets, 40 mg:

5 years.

Storage conditions.

Store at temperatures not exceeding 30 °C in the original packaging to protect from light.

Keep out of reach of children.

Packaging.

Quamatel® film-coated tablets, 20 mg:

14 tablets in a blister pack, 2 blisters per cardboard box.

Quamatel® film-coated tablets, 40 mg:

14 tablets in a blister pack, 1 blister per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Gedeon Richter Plc., Hungary.

Manufacturer's address and location of its operations.

H-1103 Budapest, Demrédi út 19–21, Hungary.