Ranitidine-zdorovya forte

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT RANITIDINE-ZDOROVYE FORTE (RANITIDINE-ZDOROVYE FORTE)

Composition:

Active substance: ranitidine;

One tablet contains ranitidine 300 mg;

Excipients: lactose monohydrate; hypromellose; sodium croscarmellose; microcrystalline cellulose; magnesium stearate; colloidal anhydrous silicon dioxide; titanium dioxide (E 171); tropaeolin 0.

Medicinal form. Film-coated tablets.

Main physicochemical properties: film-coated tablets of yellow color with a specific 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 basal and stimulated secretion of hydrochloric acid, decreasing the volume of gastric juice produced in response to stimulation of baroreceptors (gastric distension), food intake, and the action of hormones and biogenic stimulants (gastrin, histamine, pentagastrine, caffeine). Ranitidine reduces the amount of hydrochloric acid in gastric juice, does not affect plasma gastrin concentration, 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 from 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 dose), S-oxide, and is demethylated.

T½ (after oral administration) with normal creatinine clearance is 2–3 hours; when reduced (20–30 mL/min), T½ extends to 8–9 hours. It is excreted by the kidneys within 24 hours; about 30% of the orally administered dose is excreted unchanged.

Ranitidine penetrates 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 are only minimally dependent on liver function and are primarily related to kidney function.

Clinical characteristics.

Indications.

− Peptic ulcers of the stomach and duodenum 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;

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

Contraindications. Hypersensitivity to ranitidine and other components of the drug; presence of malignant diseases of the stomach, history of liver cirrhosis with portosystemic encephalopathy, liver failure, severe renal impairment (creatinine clearance < 50 ml/min).

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

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 drugs. This may either increase their absorption (triazolam, midazolam, glipizide) or decrease their absorption (ketoconazole, itraconazole, atazanavir, gefitinib).

Antacids and sucralfate slow down the absorption of ranitidine; therefore, the interval between administration of these drugs 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 prothrombin time (monitoring of prothrombin time is recommended).

High doses of ranitidine may slow down 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 in the histamine H2-receptor blocker group; therefore, the drug should be used with caution in patients with known hypersensitivity to other drugs in this class.

The drug should be used with caution in patients with acute porphyria (including history of), immunodeficiency, or phenylketonuria.

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

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

Treatment with this drug may mask symptoms of gastric carcinoma; therefore, malignancy of the stomach should be ruled out 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 compromised immune systems.

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

Ranitidine should not be used in patients with hepatic insufficiency.

The drug contains lactose. If the patient has been diagnosed with 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 affect reaction speed 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 vehicles or machinery while taking this drug.

Dosage and Administration

For adults and children aged 12 years and older, take orally without chewing, with a small amount of water, regardless of food intake.

Peptic ulcer of the stomach and duodenum, not associated with Helicobacter pylori (in the acute phase). Administer 1 tablet (300 mg) once daily at bedtime for 4 weeks. For ulcers that have not healed, continue treatment for an additional 4 weeks.

Peptic ulcer of the stomach and duodenum associated with NSAIDs. In the acute phase, administer 1 tablet (300 mg) once daily at bedtime for 8–12 weeks.

Functional dyspepsia. Administer 1 tablet (300 mg) once daily for 2–3 weeks.

Chronic gastritis with increased gastric acid secretion in the acute phase. Administer 1 tablet (300 mg) once daily for 2–4 weeks.

Gastroesophageal reflux disease (GERD). For acute episodes and long-term treatment, administer 1 tablet (300 mg) at bedtime for 8 weeks; if necessary, extend treatment up to 12 weeks.

Patients with severe renal impairment (creatinine clearance < 50 ml/min). This ranitidine dosage form is contraindicated in these patients; they should use ranitidine at a lower dose.

Children. For children aged 12 years and older, the drug is indicated to shorten 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 an increase in adverse reactions.

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

Side effects.

Blood 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, multiform exudative erythema, 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 patients or elderly patients.

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

Eye disorders: blurred vision, accommodation disturbances.

Cardiovascular system 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, itching, skin rashes, multiform erythema, alopecia, dry skin.

Musculoskeletal and connective tissue disorders: arthralgia, myalgia.

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

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 in blisters in a box.

Prescription status. 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")