Rhinit®

INSTRUCTION for medical use of the medicinal product RINIT® (RINIT®)

Composition:

Active substance: ranitidine;

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

Excipients: microcrystalline cellulose, sodium croscarmellose, magnesium stearate, Opadry II 85G53691 orange coating: polyvinyl alcohol, talc, polyethylene glycol, titanium dioxide (E 171), sunset yellow FCF (E 110), lecithin, ponceau 4R (E 124), indigocarmine (E 132).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: round, biconvex, film-coated tablets of orange color.

Pharmacotherapeutic group.

Agents for treatment of peptic ulcer and gastroesophageal reflux disease. H₂-histamine receptor antagonists. ATC code A02BA02.

Pharmacological properties.

Pharmacodynamics.

Ranitidine is an H2-histamine receptor antagonist. Its mechanism of action is due to competitive inhibition of H2-histamine receptors on parietal cells of the gastric mucosa, suppressing both basal and stimulated secretion of hydrochloric acid and reducing pepsin activity, thereby increasing the pH of gastric contents. It reduces 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). The duration of effect after a single dose is approximately 12 hours.

Pharmacokinetics.

Ranitidine is rapidly absorbed following oral administration. Absorption is not affected by food intake. Peak plasma concentrations within the range of 300–500 mcg/mL are reached within 1–3 hours after oral administration of a 150 mg dose. The bioavailability of ranitidine is 50%. Plasma concentrations of ranitidine are proportional to the administered dose. Plasma protein binding is 15%. Ranitidine is partially metabolized in the liver.

Elimination of the drug occurs primarily via the kidneys (60–70% of the oral dose), with 26% excreted in feces. The elimination half-life is 2–3 hours. Approximately 30% of the oral dose is excreted unchanged.

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 or to any of the excipients.
• Malignant gastric diseases.
• Liver cirrhosis with a history of portosystemic encephalopathy.
• Severe renal impairment (creatinine clearance < 30 mL/min).
• Hepatic impairment.

Interaction with other medicinal products and other forms of interaction.

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

Altered pharmacokinetics may require dose adjustment of the affected medicinal product or discontinuation of treatment.

Interactions occur via several mechanisms:

Inhibition of the cytochrome P450 mixed-function oxygenase system

Ranitidine, at usual therapeutic doses, does not alter the activity of the cytochrome P450 enzyme system and does not potentiate the effects of drugs inactivated by this system (e.g., diazepam, lidocaine, phenytoin, propranolol, theophylline).

Changes in prothrombin time have been reported when ranitidine is used concomitantly with coumarin anticoagulants (e.g., warfarin). Due to the narrow therapeutic index, careful monitoring of prothrombin time is recommended during concomitant treatment with ranitidine.

Competition for renal tubular secretion

Since ranitidine is partially eliminated via the cationic pathway, it may affect the clearance of other drugs eliminated by this route. High doses of ranitidine (e.g., as used in the treatment of Zollinger–Ellison syndrome) may slow the excretion of procainamide and N-acetylprocainamide, leading to increased plasma levels.

Alteration of gastric juice pH

The bioavailability of certain drugs may be altered. This may either increase absorption (e.g., triazolam, midazolam, glipizide) or decrease absorption (e.g., ketoconazole, atazanavir, delavirdine, gefitinib).

Concomitant administration of 300 mg ranitidine and erlotinib reduced erlotinib concentrations [AUC] and maximum concentrations [Cmax] by 33% and 54%, respectively. However, when erlotinib was administered 2 hours before or 10 hours after 150 mg ranitidine twice daily, erlotinib concentrations [AUC] and maximum concentrations [Cmax] decreased by only 15% and 17%, respectively.

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

If high doses (2 g) of sucralfate are taken concomitantly with ranitidine, its absorption may be reduced. This effect is not observed when sucralfate is administered with a 2-hour interval.

Special precautions for use.

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

Malignant neoplasms

Prior to initiating therapy, the presence of malignant tumors should be excluded in patients with gastric ulcer or in middle-aged or older individuals who have developed new or recently changed dyspeptic symptoms, since treatment with ranitidine may mask symptoms of gastric carcinoma.

Renal disease

Ranitidine is eliminated via the kidneys; therefore, plasma levels of ranitidine increase in patients with severe renal impairment. Dosage adjustment of ranitidine is required as described in the section "Administration and dosage".

Porphyria

Rare clinical reports suggest that ranitidine may provoke acute attacks of porphyria. Therefore, ranitidine should be avoided in patients with a history of acute porphyria.

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

An increased predisposition to the development of community-acquired pneumonia has been observed in elderly patients, individuals with chronic lung diseases, diabetes mellitus, and in those with compromised immune systems. Data indicate an increased risk of community-acquired pneumonia in patients taking ranitidine compared to those who discontinued this therapy. Post-marketing surveillance data report reversible confusion, depression, and hallucinations, which occur most frequently in severely ill and elderly patients (see section "Adverse reactions").

The medicinal product contains the colouring agents "Yellow Sunset FCF" (E 110) and "Ponceau 4R" (E 124), which may cause allergic reactions.

Use during pregnancy or breastfeeding.

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

Ability to influence reaction rate while driving or operating machinery.

Given that adverse reactions (dizziness, hallucinations, accommodation disorders) may occur in sensitive patients, patients should refrain from driving or operating machinery while taking this medicine.

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 (in the 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 nonsteroidal anti-inflammatory drugs (NSAIDs): 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 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 bedtime for 8 weeks; if necessary, continue 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 ranitidine).

Children:

In children aged 12 years and older, the medicinal product is indicated to shorten the duration of treatment of 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

Symptoms: May include intensification of adverse reactions.

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

Adverse Reactions.

Blood system disorders: reversible 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, fever, anaphylactic shock, bronchospasm, multiform exudative erythema, exfoliative dermatitis, Stevens-Johnson syndrome, Lyell's syndrome, hyperthermia, hypotension, chest pain, dyspnea.

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

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

Eye disorders: visual disturbances, reversible blurred vision, accommodation disorders.

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

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

Musculoskeletal system disorders: arthralgia, myalgia.

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

Increased plasma creatinine levels (usually mild, normalizing with continued treatment).

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

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Packaging.

10 tablets per strip, 1 strip per cardboard pack.

10 tablets per strip, 10 strips per cardboard pack.

Prescription category.

Prescription only.

Manufacturer.

KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and location of business operations.

SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.