Ranitidine

INSTRUCTIONS for medical use | consumption | of the medicinal product RANITIDINE (RANITIDINE)

Composition:

Active substance: ranitidine;

1 tablet contains 150 mg of ranitidine;

Excipients: celactose (a mixture of lactose monohydrate and powdered cellulose (75:25)), sodium croscarmellose, colloidal anhydrous silicon dioxide, magnesium stearate, hypromellose, titanium dioxide (E 171), tropaeolin 0.

Medicinal form. Film-coated tablets.

Main physico-chemical properties: film-coated tablets, yellow to orange-yellow in color, with a characteristic odor. Two layers are visible in cross-section.

Pharmacotherapeutic group. Agents for treatment of peptic ulcer and gastroesophageal reflux disease. H₂-histamine receptor antagonists. ATC code A02B A02.

Pharmacological properties.

Pharmacodynamics. Ranitidine is an anti-ulcer agent, an H₂-histamine receptor antagonist.

Its mechanism of action is due to competitive inhibition of H₂-histamine receptors on the membrane of parietal cells of the gastric mucosa. It reduces both basal and stimulated secretion of hydrochloric acid, decreasing the volume of gastric juice induced by stimulation of baroreceptors (gastric distension), food intake, and the action of hormones and biogenic stimulants (gastrin, histamine, pentagastrin, caffeine). Ranitidine reduces the amount of hydrochloric acid in gastric juice, does not affect gastrin concentration in blood plasma, or mucus production. Ranitidine is characterized by a prolonged duration of action.

Ranitidine does not affect the hepatic cytochrome P450 enzyme system.

Pharmacokinetics. After oral administration, ranitidine is rapidly absorbed in the gastrointestinal tract. Bioavailability is approximately 50%. Cmax in blood is reached within 2–3 hours and amounts to 478 ng/mL. It is partially metabolized in the liver to N-oxide (the main metabolite, 4% of the dose), S-oxide, and by demethylation.

The half-life (after oral administration) is 2–3 hours with normal creatinine clearance, and 8–9 hours with reduced clearance (20–30 mL/min). It is excreted by the kidneys within 24 hours, with about 30% of the orally administered dose being eliminated unchanged.

Ranitidine penetrates through histohematogenous barriers, including the placental barrier, but poorly crosses the blood-brain barrier. Significant concentrations are detected in breast milk. The rate and extent of elimination depend minimally on liver function and are primarily related to kidney function.

Clinical characteristics.

Indications.

− Gastric and duodenal peptic ulcers not associated with Helicobacter pylori (in the acute phase), including ulcers associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs);

− functional dyspepsia;

− chronic gastritis with increased gastric acid secretion in the acute phase;

|ulcers|

− gastroesophageal reflux disease (for symptom relief) or reflux esophagitis.

Contraindications. Hypersensitivity to ranitidine and other components of the drug; malignant diseases of the stomach, liver cirrhosis with portosystemic encephalopathy in medical history, hepatic insufficiency, severe renal insufficiency (creatinine clearance < 30 ml/min).

Interaction with other medicinal products and other types of interactions. Ranitidine may affect the absorption, metabolism, and renal excretion of other medicinal products.

Ranitidine in therapeutic doses does not alter the activity of the cytochrome P450 enzyme system and does not potentiate the effect of drugs metabolized by this system (diazepam, lidocaine, phenytoin, propranolol, theophylline).

Ranitidine, by altering gastric acidity, may affect the bioavailability of certain medicinal products. This may either increase their absorption (triazolam, midazolam, glipizide) or reduce their absorption (ketoconazole, itraconazole, atazanavir, gefitinib).

Antacids and sucralfate delay the absorption of ranitidine; therefore, the interval between administration of these medicinal products and ranitidine should be at least 1–2 hours.

Concomitant use with metoprolol may lead to increased metoprolol concentration in blood serum.

Ranitidine, when used concomitantly with coumarin anticoagulants (warfarin), may alter the prothrombin time (monitoring of prothrombin time is recommended).

High doses of ranitidine may slow the excretion of procainamide and N-acetylprocainamide, leading to increased plasma levels.

Data on the interaction between ranitidine and amoxicillin or metronidazole are lacking.

Tobacco smoking reduces the effectiveness of ranitidine.

Special precautions for use.

Allergic reactions to ranitidine may occur in patients with allergies to other drugs from the histamine H2-receptor antagonist group; therefore, the drug should be used with caution in patients with hypersensitivity to other drugs of this class.

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

Ranitidine is eliminated by the kidneys; therefore, in patients with severe renal impairment, its plasma levels are elevated (see dosing recommendations for such patients in the section "Administration and dosage").

In elderly patients with impaired liver or kidney function, confusion may occur, necessitating dose reduction.

Treatment with this drug may mask symptoms of gastric carcinoma; therefore, the possibility of malignant gastric tumors should be excluded before initiating therapy.

Regular monitoring is required for patients (especially elderly patients and those with a history of gastric and/or duodenal peptic ulcer) who are taking ranitidine concomitantly with NSAIDs.

An increased risk of community-acquired pneumonia has been observed in elderly patients, individuals with chronic lung diseases, diabetes mellitus, or those with weakened immunity.

The drug treatment should be discontinued gradually due to the risk of rebound syndrome following abrupt discontinuation.

The drug contains lactose. If a patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding. The drug is contraindicated during pregnancy. If use of the drug is necessary, breastfeeding should be discontinued.

Ability to influence reaction rate when driving or operating machinery. Given that adverse reactions (dizziness, hallucinations, accommodation disorders) may occur in sensitive patients during treatment, patients should refrain from driving or operating machinery while taking this drug.

Dosage and Administration

For use in adults and children aged 12 years and older. Take orally, without chewing, with a small amount of water, independent of food intake.

Peptic ulcer of the stomach and duodenum not associated with Helicobacter pylori (during acute phase): Administer 150 mg (1 tablet) twice daily in the morning and evening, or 300 mg (2 tablets) once daily at bedtime for 4 weeks. For non-healing ulcers, continue treatment for an additional 4 weeks.

Prophylaxis of peptic ulcer of the stomach and duodenum associated with NSAID use: Administer 150 mg (1 tablet) twice daily in the morning and evening throughout the duration of NSAID therapy.

Functional dyspepsia: Administer 150 mg (1 tablet) twice daily in the morning and evening for 2–3 weeks.

Chronic gastritis with increased gastric acid secretion in the acute phase: Administer 150 mg (1 tablet) twice daily in the morning and evening for 2–4 weeks.

Gastroesophageal reflux disease (GERD): To relieve symptoms, administer 150 mg (1 tablet) twice daily in the morning and evening for 2 weeks; if necessary, continue treatment.

For long-term treatment and during exacerbations of gastroesophageal reflux disease, administer 150 mg (1 tablet) twice daily in the morning and evening, or 300 mg (2 tablets) once daily at bedtime for 8 weeks; if necessary, extend treatment up to 12 weeks.

Patients with severe renal impairment (creatinine clearance < 50 ml/min): The daily dose for this patient group is 1 tablet (150 mg of ranitidine).

Children. For children aged 12 years and older, the drug is indicated to shorten healing time of peptic ulcers of the stomach and duodenum, for the treatment of gastroesophageal reflux disease including reflux esophagitis, and for symptom relief of gastroesophageal reflux disease.

Overdose. May result in intensification of adverse reactions.

Treatment: if necessary, provide appropriate symptomatic and supportive therapy. Ranitidine can be removed from the blood plasma by hemodialysis.

Adverse Reactions.

Blood and lymphatic system disorders: leukopenia, reversible thrombocytopenia, agranulocytosis or pancytopenia, sometimes with hypoplasia or aplasia of the bone marrow, neutropenia, immune hemolytic and aplastic anemia (usually reversible).

Immune system disorders: hypersensitivity reactions, including urticaria, angioedema, fever, anaphylactic shock, bronchospasm, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, Lyell's syndrome, hyperthermia.

Psychiatric disorders: increased fatigue, reversible confusion, drowsiness, excitement, insomnia, emotional lability, restlessness, anxiety, depression, nervousness, hallucinations, tinnitus, irritability, disorientation, disoriented state. These manifestations are mainly observed in severely ill or elderly patients.

Nervous system disorders: headache, dizziness, and reversible involuntary movement disorders.

Eye disorders: blurred vision, accommodation disturbances.

Cardiac and vascular disorders: decreased arterial pressure, bradycardia, tachycardia, asystole, atrioventricular block, vasculitis, chest pain, arrhythmia, extrasystole.

Gastrointestinal disorders: dry mouth, nausea, vomiting, constipation, diarrhea, abdominal pain, flatulence, acute pancreatitis, decreased appetite.

Hepatobiliary disorders: transient and reversible changes in liver function tests; hepatocellular, cholestatic, or mixed hepatitis with or without jaundice (usually reversible).

Skin and subcutaneous tissue disorders: hyperemia, pruritus, skin rashes, erythema multiforme, alopecia, dry skin.

Musculoskeletal and connective tissue disorders: arthralgia, myalgia.

Renal and urinary disorders: renal function impairment, acute interstitial nephritis.

Reproductive system disorders: hyperprolactinemia, galactorrhea, gynecomastia, amenorrhea, decreased potency (reversible) and/or libido.

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. Tablets | tablets | No. 10, No. 10×2, No. 20 in blister packs in a box.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Limited Liability Company "FARMEKS GROUP".

Manufacturer's address and place of business.

Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, 22.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA")

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

(Limited Liability Company "FARMEKS GROUP")