Ranitidine euro

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT RANITIDINE EURO (RANITIDINE EURO)

Composition:

Active substance: ranitidine;

One 150 mg film-coated tablet contains ranitidine hydrochloride equivalent to ranitidine 150 mg;

One 300 mg film-coated tablet contains ranitidine hydrochloride equivalent to ranitidine 300 mg;

Excipients: 150 mg or 300 mg tablets: microcrystalline cellulose, magnesium stearate, sodium croscarmellose, Opadry Orange 80W53259 AMB (polyvinyl alcohol, talc, titanium dioxide (E 171), Yellow West FCF dye (E 110), lecithin (E 332), aluminium lake (E 173), xanthan gum, iron oxide red (E 172)), talc.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: round, biconvex, orange-colored tablets, film-coated.

Pharmacotherapeutic group. Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. H₂-receptor antagonists.

ATC code A02B A02.

Pharmacological Properties

Pharmacodynamics

The active component of the drug, ranitidine, is an H₂-histamine receptor blocker of gastric mucosal parietal cells. The mechanism of action of ranitidine involves competitive, reversible inhibition of histamine action at H₂-receptors on the membranes of parietal cells in the gastric mucosa.

Ranitidine reduces both basal and stimulated hydrochloric acid secretion induced by baroreceptor stimulation, food intake, and the action of hormones and biogenic stimulants (gastrin, histamine, pentagastrin, caffeine). It decreases the volume of gastric juice and its hydrochloric acid content, increases the pH of gastric contents, thereby reducing pepsin activity. It does not affect plasma gastrin concentration or mucus production. At therapeutic oral doses, it does not influence prolactin levels. The drug inhibits microsomal enzymes. The duration of action after a single dose is up to 12 hours.

Ranitidine does not affect the hepatic cytochrome P450 enzyme system.

Pharmacokinetics

The drug is rapidly absorbed, and food intake does not affect the extent of absorption. After oral administration, the bioavailability of ranitidine is approximately 50%. Maximum plasma concentration is reached within 2–3 hours after administration. Plasma protein binding does not exceed 15%. Ranitidine is minimally metabolized in the liver, forming N-oxide, desmethylranitidine, and S-oxides of ranitidine. It exhibits a first-pass effect through the liver. The rate and extent of elimination are minimally dependent on liver function. The elimination half-life after oral administration is 2–3 hours; when creatinine clearance is 20–30 mL/min, the half-life extends to 8–9 hours. The drug is excreted by the kidneys within 24 hours, primarily in urine (60–70%, of which 35% is unchanged), with a small amount excreted in feces.

Ranitidine poorly crosses the blood-brain barrier but crosses the placental barrier. It is excreted into breast milk (concentrations in breast milk during lactation are higher than those in maternal plasma).

The rate and extent of elimination are minimally influenced by liver function and are primarily related to renal function.

In patients aged 50 years and older, the elimination half-life is prolonged (3–4 hours), and clearance is reduced corresponding to age-related decline in renal function. However, systemic exposure and accumulation are about 50% higher. This difference exceeds the effect of reduced renal function and also indicates increased bioavailability in elderly patients.

Clinical characteristics.

Indications.

• Gastric and duodenal peptic ulcer 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 to other components of the drug; presence of malignant diseases of the stomach, history of liver cirrhosis with portosystemic encephalopathy, hepatic insufficiency, severe renal insufficiency (creatinine clearance <50 mL/min).

Interaction with other medicinal products and other forms of interaction.

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 action of drugs metabolized by this system (diazepam, lidocaine, phenytoin, propranolol, theophylline, etc.).

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

Ranitidine increases the plasma concentration of metoprolol when used concomitantly.

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.

Smoking reduces the effectiveness of ranitidine.

Special precautions for use.

Allergic reactions to ranitidine may occur in patients with a history of allergy to other drugs from the H2-receptor blocker group; therefore, the drug should be used with caution in patients with known hypersensitivity to other agents of this class.

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

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

Since ranitidine is metabolized in the liver, it should be used with caution in patients with severe hepatic dysfunction.

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 peptic ulcer of the stomach and/or duodenum) who are taking ranitidine concomitantly with nonsteroidal anti-inflammatory drugs.

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

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.

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

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, Ranitidine Europe tablets should not be prescribed to patients who drive vehicles or operate potentially hazardous machinery, as well as those engaged in other activities requiring high concentration and rapid psychomotor responses.

Administration and Dosage.

For use in 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 (during exacerbation phase). Administer 150 mg twice daily (morning and evening) or 300 mg at bedtime for 4 weeks. For non-healing ulcers, continue treatment for an additional 4 weeks.

Peptic ulcer of the stomach and duodenum associated with nonsteroidal anti-inflammatory drugs (NSAIDs). Administer 150 mg twice daily or 300 mg at bedtime during NSAID therapy (for 8–12 weeks).

Functional dyspepsia. Administer 150 mg twice daily or 300 mg once daily for 2–3 weeks.

Chronic gastritis with increased gastric acid secretion in the exacerbation phase. Administer 150 mg twice daily or 300 mg once daily for 2–4 weeks.

Gastroesophageal reflux disease (GERD). To relieve symptoms, administer 150 mg twice daily for 2 weeks; if necessary, extend the treatment course. For exacerbation and long-term treatment, administer 150 mg twice daily or 300 mg 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 150 mg.

Children.

Children aged 12 years and older may be prescribed the drug to shorten the duration of treatment for peptic ulcer 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.

Exaggeration of adverse reactions.

Treatment: provide appropriate symptomatic and supportive therapy.

The drug may be removed by hemodialysis.

Adverse Reactions

Cardiovascular system: bradycardia, tachycardia, extrasystoles, asystole, arterial hypotension, atrioventricular block, arrhythmia, vasculitis, chest pain.

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

Nervous system: headache (sometimes severe), dizziness, somnolence, involuntary movements (reversible), excitement, fatigue.

Eye disorders: blurred vision, visual disturbances, clouding of vision associated with accommodation disorder.

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

Renal and urinary system: acute interstitial nephritis, renal function impairment, increased plasma creatinine levels (usually mild, normalize with continued treatment).

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

Musculoskeletal system: arthralgia, myalgia.

Immune system: hypersensitivity reactions (urticaria, angioneurotic edema, fever, bronchospasm, arterial hypotension, chest pain), urticaria, anaphylactic shock, erythema multiforme exudativum, exfoliative dermatitis, Stevens-Johnson syndrome, Lyell's syndrome, hyperthermia, dyspnea.

Hepatobiliary system: transient and reversible changes in levels of certain laboratory parameters (transaminases, gamma-glutamyl transferase, alkaline phosphatase, bilirubin); hepatitis (hepatocellular, cholestatic, or mixed hepatitis), with or without jaundice (usually reversible).

Reproductive system: hyperprolactinemia, decreased potency and/or libido, gynecomastia, galactorrhea, amenorrhea.

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

Shelf life. 3 years.

Storage conditions. Store at a temperature not exceeding 30 °C in the original packaging. Keep out of reach of children.

Packaging.

For 150 mg dosage: 10 tablets in blisters; 2, 5, or 10 blisters in a cardboard box.

For 300 mg dosage: 10 tablets in blisters; 2 or 5 blisters in a cardboard box.

Prescription category. Prescription only.

Manufacturer. Unique Pharmaceuticals Laboratories (a division of "J. B. Chemicals and Pharmaceuticals Ltd.").

Manufacturer's address. Plot No. 215-219, G.I.D.C. Industrial Area, Panoli – 394 116, Bharuch District, India.