Famotidine-zdorovya

INSTRUCTION FOR MEDICAL USE | consumption | of the medicinal product FAMOTIDINE-ZDOROV'YA (FAMOTIDINE-ZDOROVYE)

Composition:

Active substance: famotidine;

1 tablet contains famotidine 20 mg;

Excipients: microcrystalline cellulose, lactose monohydrate, copovidone, sodium croscarmellose, magnesium stearate, anhydrous colloidal silicon dioxide, azorubine (E 122); dry mixture "Opadry II white" containing titanium dioxide (E 171), talc, polyethylene glycol, polyvinyl alcohol.

Dosage form. Coated tablets.

Main physico-chemical properties: coated tablets of pink to dark pink color. Two layers are visible in cross-section.

Pharmacotherapeutic group. Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. H2-receptor antagonists. Famotidine. ATC code A02B A03.

Pharmacological Properties

Pharmacodynamics. Famotidine is a selective H2-histamine receptor antagonist of the third generation.

Its mechanism of action is due to competitive inhibition of H2-histamine receptors in the gastric wall, thereby reducing gastric juice secretion (its volume). It suppresses both basal and stimulated hydrochloric acid production and increases the pH of gastric juice. Simultaneously, it reduces pepsin activity.

It enhances protective mechanisms of the gastric mucosa by increasing gastric mucus production and glycoprotein content within it, promoting healing of mucosal damage (including scarring of stress ulcers).

After oral administration, the effect begins within 1 hour, reaches maximum within 3 hours, and lasts, depending on the dose, from 10 to 24 hours. The action of famotidine at a dose of 20–40 mg lasts for 10–12 hours.

Pharmacokinetics. After oral administration, famotidine is rapidly absorbed in the gastrointestinal tract; concomitant food intake does not affect absorption. Cmax in plasma is reached within 1–3 hours. Protein binding in blood is 15–20%. Relative bioavailability of famotidine is 40–45%. Gastric filling status does not affect bioavailability. Famotidine penetrates into cerebrospinal fluid, crosses the placental barrier, and is excreted into breast milk.

The drug is metabolized in the liver, forming an inactive sulfone metabolite. It is primarily excreted by the kidneys (65–70%) via glomerular filtration and tubular secretion; 25–30% of the administered dose is excreted unchanged. The plasma half-life (T½) is approximately 3 hours.

In patients with severe renal impairment (creatinine clearance less than 10 ml/min), T½ is prolonged and may exceed 20 hours; in patients with anuria, it is approximately 24 hours.

Clinical characteristics.

Indications.

• Benign gastric ulcer.
• Duodenal peptic ulcer (treatment and prevention of recurrences).
• Hypersecretory conditions, such as Zollinger–Ellison syndrome.
• Treatment of gastroesophageal reflux disease (reflux esophagitis).
• Prevention of symptoms and of erosions or ulcer formation associated with gastroesophageal reflux disease.

Contraindications. Hypersensitivity to the components of the drug, other H2-histamine receptor antagonists.

Paediatric age, pregnancy or lactation period (due to lack of necessary 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 juice acidity. Therefore, famotidine should be administered at least 2 hours after intake of 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 an interaction 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 have a significant effect on famotidine therapy.

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 slow the elimination of famotidine.

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

Concomitant use of famotidine with tyrosine kinase inhibitors (TKIs), such as dasatinib, erlotinib, gefitinib, 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 additional recommendations, refer to the prescribing information of individual medicinal products containing TKIs.

Special precautions for use.

Treatment with the drug may mask the symptoms of gastric malignancy; therefore, the presence of stomach cancer must be excluded before initiating therapy.

The drug should be used with caution and in lower doses in patients with hepatic impairment.

Use with caution in patients with acute porphyria (including history thereof) and immunodeficiency.

Cross-sensitivity between H2-receptor antagonists has been reported; therefore, famotidine is contraindicated in patients with hypersensitivity to other H2-receptor antagonists.

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

Regular monitoring is necessary for patients (especially elderly patients and those with a history of peptic ulcer of the stomach and/or duodenum) who are receiving the drug concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs).

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

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

Treatment with this drug should not be initiated without a physician's prescription or without prior appropriate medical evaluation in patients with kidney or liver disease. In elderly patients with impaired liver or kidney function, confusion may occur, requiring dose reduction. Treatment should also be avoided without medical evaluation in elderly patients presenting with heartburn, symptoms of hyperacidic state, stomach pain, or postprandial hyperacidity, as well as in cases of changes in the nature of these symptoms; in patients reporting gastric discomfort accompanied by weight loss; in patients with black-colored stools; or in patients with dysphagia and/or chronic abdominal pain.

The drug contains lactose. If a patient has known sugar intolerance, consultation with a physician is recommended before taking this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy. Famotidine crosses the placenta.

Pregnancy. Famotidine crosses the placenta.

Pregnancy. Famotidine crosses the placenta.

Pregnancy. Famotidine crosses the placenta. Adequate and well-controlled studies in pregnant women have not been conducted. The drug is not recommended during pregnancy.

Breastfeeding. Famotidine is excreted in human breast milk; therefore, breastfeeding should be discontinued during treatment with this drug.

Effect on ability to drive and operate machinery. Patients should exercise caution when performing potentially hazardous activities that require heightened attention and rapid psychomotor responses, as this drug may cause dizziness.

Dosage and Administration

Administer orally, without chewing, with sufficient amount of water, regardless of food intake.

Treatment of benign gastric ulcer and duodenal peptic ulcer. Administer 40 mg (2 tablets) once daily at bedtime for 4–8 weeks.

For prevention of relapses after achievement of therapeutic effect, administer a maintenance dose of 20 mg (1 tablet) once daily at bedtime for 1–4 weeks.

Gastroesophageal reflux disease (GERD) (reflux esophagitis). Administer 20 mg (1 tablet) or 40 mg (2 tablets) (depending on disease severity) twice daily (in the morning and evening) for 6–12 weeks. For gastroesophageal reflux disease associated with erosive esophagitis or ulceration, administer 40 mg (2 tablets) twice daily for 6–12 weeks.

Prevention of symptoms and development of erosions or ulceration associated with gastroesophageal reflux disease. Administer 20 mg (1 tablet) twice daily.

Zollinger–Ellison syndrome. The dosage should be individually adjusted. For patients who have not previously received antisecretory drugs, initiate treatment with a dose of 20 mg (1 tablet) four times daily (every 6 hours). For patients previously treated with other H₂-receptor antagonists, a higher initial dose may be immediately prescribed—40 mg (2 tablets) every 6 hours. Subsequently, adjust the dose according to gastric juice secretion levels and the patient's clinical condition. Treatment should continue as long as clinical symptoms of the disease are present.

If necessary, gradually increase the daily dose according to individual response until the optimal dose is achieved. Data exist that the highest doses of famotidine taken by patients with severe forms of the disease reached up to 160 mg every 6 hours.

Discontinue the drug gradually to avoid the risk of rebound syndrome following abrupt withdrawal.

Patients with severe renal impairment (creatinine clearance less than 30 mL/min, serum creatinine level above 3 mg/100 mL), reduce the daily dose to 20 mg or extend the dosing interval to 36–48 hours.

Elderly patients do not require dose adjustment unless they have renal impairment.

Children. Do not administer the drug to children due to lack of experience with its use in this patient population.

Overdose.

Symptoms: vomiting, motor agitation, tremor, decreased arterial pressure, tachycardia, collapse.

Treatment: discontinue the drug, induce vomiting and/or perform gastric lavage. If necessary, provide appropriate symptomatic and supportive therapy: administer intravenous diazepam in case of seizures; atropine in case of bradycardia; lidocaine in case of ventricular arrhythmias. Hemodialysis is effective.

Adverse Reactions

The drug is generally well tolerated; however, the following adverse reactions may occur:

Blood system disorders: thrombocytopenia, agranulocytosis, pancytopenia, leukopenia, neutropenia.

Gastrointestinal disorders: dry mouth, nausea, vomiting, dysgeusia, cholestatic jaundice, acute pancreatitis, hepatitis, diarrhea, constipation, anorexia, flatulence, stomach pain, increased levels of liver enzymes.

Nervous system disorders: headache, dizziness, convulsions, paresthesia, disturbances of equilibrium.

Psychiatric disorders: depression, hallucinations, excitation, fear, insomnia, somnolence, confusion.

General disorders: fatigue, fever.

Sensory organ disorders: conjunctivitis, tinnitus.

Cardiovascular disorders: arrhythmia, atrioventricular block, decreased blood pressure, bradycardia, tachycardia.

Respiratory system disorders: airway obstruction.

Skin disorders: acne, alopecia, dry skin, pruritus, rash, Lyell's syndrome, Stevens-Johnson syndrome, exfoliative dermatitis, erythema, xeroderma.

Musculoskeletal system disorders: myalgia, bone pain or arthralgia.

Reproductive system and breast disorders: gynecomastia (very rare and reversible upon discontinuation of treatment); decreased libido, impotence.

Immune system disorders: hypersensitivity reactions including anaphylaxis, angioneurotic edema, urticaria, eye swelling.

If any serious adverse reactions occur, treatment with the drug must be discontinued.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 tablets per blister; 1 or 2 blisters per cardboard box; 20 tablets per blister; 1 blister per cardboard box.

Prescription category. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Limited Liability Company "FARMEKS GROUP".

Manufacturer's address and location of business activity. Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, building 22.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA")

Ukraine, 08301, Kyiv region, city of Boryspil, Shevchenka Street, building 100.

(Limited Liability Company "FARMEKS GROUP")