Ranitidine-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RANITIDINE-DARNITSA (RANITIDINE-DARNITSA)

Composition:

Active substance: ranitidine;

1 tablet contains ranitidine hydrochloride equivalent to 150 mg of ranitidine;

Excipients: microcrystalline cellulose, povidone, lactose monohydrate, potato starch, talc, magnesium stearate, Opadry AMB 80 W yellow.

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties: yellow to yellow-orange, round, biconvex film-coated tablets. Cross-section reveals two layers.

Pharmacotherapeutic group. Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. H2-histamine receptor antagonists. Ranitidine. ATC code A02BA02.

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 membranes of parietal cells in 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 plasma gastrin concentration, and does not influence 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%. Maximum plasma concentration 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 undergoes demethylation.

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

Ranitidine penetrates through histohematogenous barriers, including the placental barrier, but poorly crosses the blood-brain barrier. Clinically 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 ulcer not associated with Helicobacter pylori (in the acute phase), including ulcers related to the use of nonsteroidal anti-inflammatory drugs (NSAIDs);
• functional dyspepsia;
• chronic gastritis with increased gastric acid secretion in the acute phase;
• gastroesophageal reflux disease (for symptom relief) or reflux esophagitis.

Contraindications.

Hypersensitivity to ranitidine and other components of the drug; presence of malignant gastric diseases; history of liver cirrhosis with portosystemic encephalopathy; hepatic insufficiency; severe renal insufficiency (creatinine clearance < 30 mL/min).

Interaction with other medicinal products and other forms of interactions.

Ranitidine may affect the absorption, metabolism, and renal excretion of other medicinal products.

Ranitidine, at therapeutic doses, does not alter the activity of the cytochrome P450 enzyme system and does not potentiate the effects 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 lead either to increased absorption (triazolam, midazolam, glipizide) or decreased 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 serum concentrations.

Ranitidine, when used concomitantly with coumarin anticoagulants (warfarin), may alter 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 of these substances.

Data on interactions between ranitidine and amoxicillin or metronidazole are lacking.

Tobacco smoking reduces the effectiveness of ranitidine.

Special precautions for use.

Allergic reactions to ranitidine are possible in patients with a history of allergy to other histamine H2-receptor antagonists; therefore, the drug should be used with caution in patients with known hypersensitivity to other drugs of this class.

Use the drug with caution in patients with acute porphyria (including in medical history), immunodeficiency, or phenylketonuria.

Ranitidine is excreted by the kidneys; therefore, in patients with severe renal impairment, its plasma levels are increased (see dosage recommendations for such patients in the section "Dosage and administration").

Confusion may occur in elderly patients with impaired liver or kidney function, necessitating dose reduction.

Ranitidine treatment may mask symptoms of gastric carcinoma; therefore, malignancy of the stomach 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.

Plasma theophylline levels should be monitored and dosage adjusted when ranitidine is used concomitantly with theophylline.

An increased risk of developing community-acquired pneumonia has been observed in elderly patients, patients with chronic lung diseases, diabetes mellitus, or those with compromised immune systems.

Ranitidine therapy should be discontinued gradually due to the risk of rebound syndrome following abrupt discontinuation.

Ranitidine should not be used in patients with hepatic insufficiency.

Important information about excipients.

The medicinal product contains lactose, which should be taken into account in patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

If a patient has been diagnosed with intolerance to certain sugars, they should consult a physician 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.

Effect on ability to drive or operate 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 medicinal product.

Method of Administration and Dosage

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

Peptic ulcer of the stomach and duodenum, not associated with Helicobacter pylori (in the acute phase): Administer 150 mg (1 tablet) twice daily in the morning and evening, or 300 mg (2 tablets) once at night 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): For symptom relief, administer 150 mg (1 tablet) twice daily in the morning and evening for 2 weeks; if necessary, extend the treatment course.

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 night for 8 weeks; if necessary, extend the treatment course up to 12 weeks.

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

Children

The use of the drug in children aged 12 years and older is indicated for shortening the healing time of peptic ulcers of the stomach and duodenum, for the treatment of gastroesophageal reflux disease, including reflux esophagitis, and for relief of symptoms 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 blood serum by hemodialysis.

Side effects.

Eye disorders: blurred vision, accommodation disorders.

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

Hepatobiliary disorders: transient and reversible changes in liver function parameters (transaminases, gamma-glutamyl transferase, alkaline phosphatase, bilirubin), hepatocellular, cholestatic or mixed hepatitis with or without jaundice (usually reversible).

Renal and urinary disorders: renal dysfunction, acute interstitial nephritis, increased plasma creatinine levels.

Nervous system disorders: headache (sometimes severe), dizziness, reversible involuntary movement disorders.

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

Cardiovascular disorders: decreased blood pressure, bradycardia, tachycardia, asystole, atrioventricular block, vasculitis, chest pain, arrhythmia, extrasystoles.

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, angioneurotic edema, anaphylactic shock, bronchospasm, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), hyperthermia.

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

Musculoskeletal and connective tissue disorders: arthralgia, myalgia.

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

General disorders: fever.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization is an important procedure. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 2 years.

Storage conditions.

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

Packaging.

10 tablets in a blister pack; 1 or 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical company "Darnytsia".

Manufacturer's address and location of business activity.

13 Boryspylska Street, Kyiv, 02093, Ukraine.