Rantac^® (Solution) Instructions for Use

Marketing Authorization Holder

Unique Pharmaceutical Laboratories (India)

Company Division

J. B. Chemicals & Pharmaceuticals, Ltd. (India)

ATC Code

A02BA02 (Ranitidine)

Active Substance

Ranitidine (Rec.INN registered by WHO)

Dosage Forms

	Rantac®	Solution for intravenous and intramuscular administration 50 mg/2 ml: amp. 10 pcs.
		Film-coated tablets, 150 mg: 20 or 50 pcs.
		Film-coated tablets, 300 mg: 20 or 50 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets orange, round, biconvex.

Excipients: microcrystalline cellulose, corn starch, hypromellose, Opadry-OY-53020 orange, purified talc.

10 pcs. – strips (2) – packs.
10 pcs. – strips (5) – packs.

Film-coated tablets orange, round, biconvex.

Excipients: microcrystalline cellulose, corn starch, hypromellose, Opadry-OY-53020 orange, purified talc.

10 pcs. – strips (2) – packs.
10 pcs. – strips (5) – packs.

Solution for IV and IM administration clear, from colorless to yellow.

Excipients: phenol, potassium dihydrogen phosphate, sodium hydrogen phosphate, water for injections.

2 ml – ampoules (10) – packs.

Clinical-Pharmacological Group

Histamine H₂-receptor blocker. Antiulcer drug

Pharmacotherapeutic Group

H2 histamine receptor blocker

Pharmacological Action

Ranitidine blocks histamine H₂-receptors of parietal cells of the gastric mucosa, reduces basal and stimulated secretion of hydrochloric acid caused by baroreceptor irritation, food load, action of hormones and biogenic stimulants (gastrin, histamine, pentagastrin).

Ranitidine reduces the volume of gastric juice and the content of hydrochloric acid in it, increases the pH of the stomach contents, which leads to a decrease in pepsin activity. After oral administration in therapeutic doses, it does not affect prolactin levels. Inhibits microsomal enzymes.

The duration of action after a single dose is up to 12 hours.

Pharmacokinetics

Rapidly absorbed, food intake does not affect the degree of absorption. When taken orally, the bioavailability of ranitidine is approximately 50%. C_max in plasma is reached 2-3 hours after administration. Plasma protein binding does not exceed 15%.

Slightly metabolized in the liver to form desmethylranitidine and ranitidine S-oxide. Has a first-pass effect through the liver. The rate and extent of elimination are slightly dependent on the state of the liver. T_1/2 after oral administration is 2.5 hours, with a creatinine clearance of 20-30 ml/min – 8-9 hours.

It is excreted mainly in the urine (60-70%, 35% unchanged), a small amount – in the feces.

When administered intravenously, 93% of the dose is excreted in the urine, and 70% of ranitidine is excreted unchanged.

Penetrates poorly through the BBB. Penetrates through the placenta. Excreted in breast milk (the concentration in breast milk in lactating women is higher than in plasma).

Indications

Tablets

• Treatment and prevention of exacerbations of gastric and duodenal ulcers;
• Gastric and duodenal ulcers associated with the use of non-steroidal NSAIDs;
• Reflux esophagitis, erosive esophagitis;
• Zollinger-Ellison syndrome;
• Treatment and prevention of postoperative, stress ulcers of the upper gastrointestinal tract;
• Prevention of recurrent bleeding from the upper gastrointestinal tract;
• Prevention of gastric juice aspiration during operations under general anesthesia (Mendelson’s syndrome).

Solution for IV and IM administration

• Prevention of bleeding from stress ulcers and recurrent bleeding in patients with gastric and duodenal ulcers;
• Prevention of the development of Mendelson’s syndrome.

ICD codes

Dosage Regimen

Tablets

Rantac^® is taken regardless of meals, without chewing, with a small amount of liquid.

Adults and children over 12 years

Gastric and duodenal ulcer. For treatment of exacerbations, 150 mg 2 times/day (morning and evening) or 300 mg at night is prescribed. If necessary – 300 mg 2 times/day. The duration of the treatment course is 4-8 weeks. For prevention of exacerbations, 150 mg at night is prescribed, for smoking patients – 300 mg at night.

Ulcers associated with NSAID use. Prescribe 150 mg 2 times/day or 300 mg at night for 8-12 weeks. Prevention of ulcer formation when taking NSAIDs – 150 mg 2 times/day.

Postoperative and stress ulcers. Prescribe 150 mg 2 times/day for 4-8 weeks.

Erosive reflux esophagitis. Prescribe 150 mg 2 times/day or 300 mg at night. If necessary, the dose can be increased to 150 mg 4 times/day. The course of treatment is 8-12 weeks. Long-term preventive therapy – 150 mg 2 times/day.

Zollinger-Ellison syndrome. The initial dose is 150 mg 3 times/day, if necessary, the dose can be increased. The duration of treatment is as needed.

Prevention of recurrent bleeding. 150 mg 2 times/day. The duration of treatment is as needed.

Prevention of the development of Mendelson’s syndrome. Prescribed in a dose of 150 mg 2 hours before anesthesia, and also preferably 150 mg the night before.

In case of concomitant impaired liver function, a dose reduction may be required.

For patients with renal failure with creatinine clearance less than 50 ml/min, the recommended dose is 150 mg once/day.

Solution for IM and IV administration

Prevention of bleeding from stress ulcers and recurrent bleeding in patients with gastric and duodenal ulcers.

IM injections: 50 mg (2 ml) every 6-8 hours.

IV injections: 50 mg (2 ml) every 6-8 hours. The contents of the ampoule (50 mg) are diluted with 0.9% sodium chloride solution or dextrose for injection to a total volume of 20 ml and slowly administered over 5 minutes. The drug is prescribed parenterally until oral administration is impossible.

Prevention of the development of Mendelson’s syndrome. 50 mg IM or IV 45-60 minutes before general anesthesia.

For patients with renal failure with creatinine clearance less than 50 ml/min, the recommended single dose is 25 mg.

Adverse Reactions

From the digestive system: nausea, dry mouth, constipation, vomiting, diarrhea, abdominal pain, increased activity of liver transaminases, hepatocellular, cholestatic or mixed hepatitis, acute pancreatitis.

From the hematopoietic organs: leukopenia, thrombocytopenia, agranulocytosis, pancytopenia, hypo- and aplasia of the bone marrow, immune hemolytic anemia.

From the cardiovascular system: decreased blood pressure, bradycardia, arrhythmia, AV block, asystole (with parenteral administration).

From the CNS: increased fatigue, drowsiness, headache, dizziness, confusion, irritability, hallucinations (mainly in elderly patients and severely ill patients), involuntary movements.

From the senses: blurred vision, accommodation paresis, tinnitus.

From the musculoskeletal system: arthralgia, myalgia.

From the endocrine system: hyperprolactinemia, gynecomastia, amenorrhea, decreased libido, impotence.

Allergic reactions: urticaria, skin rash, angioedema, anaphylactic shock, bronchospasm, multiforme exudative erythema.

Other: alopecia, hypercreatininemia, increased activity of glutamyl transpeptidase, acute porphyria.

Contraindications

• Pregnancy;
• Lactation period;
• Children under 12 years of age;
• Hypersensitivity to ranitidine or other components of the drug.

With caution – renal and/or hepatic impairment, liver cirrhosis with a history of portosystemic encephalopathy, acute porphyria (including history).

Use in Pregnancy and Lactation

Contraindicated.

Use in Hepatic Impairment

With caution – hepatic impairment, liver cirrhosis with a history of portosystemic encephalopathy, acute porphyria (including history).

In case of concomitant impaired liver function, a dose reduction may be required.

Use in Renal Impairment

With caution – renal failure.

Pediatric Use

The safety and efficacy of ranitidine in children under 12 years of age have not been established.

Special Precautions

Treatment with ranitidine may mask symptoms associated with gastric carcinoma, so before starting treatment, it is necessary to exclude the presence of a malignant neoplasm.

Ranitidine should not be abruptly discontinued (rebound syndrome).

During long-term treatment of debilitated patients under stress, bacterial lesions of the stomach with subsequent spread of infection are possible.

Histamine H₂-receptor blockers should be taken 2 hours after taking itraconazole or ketoconazole to avoid a significant reduction in their absorption.

Taking ranitidine may cause a false-positive reaction when testing for protein in the urine.

Histamine H₂-receptor blockers may counteract the effect of pentagastrin and histamine on gastric acid production, so it is not recommended to use histamine H₂-receptor blockers within 24 hours preceding the test.

Histamine H₂-receptor blockers may suppress the skin reaction to histamine, thus leading to false-positive results (before performing diagnostic skin tests to detect an immediate allergic skin reaction, it is recommended to discontinue the use of histamine H₂-receptor blockers).

The safety and efficacy of ranitidine in children under 12 years of age have not been established.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: convulsions, bradycardia, ventricular arrhythmias.

Treatment: symptomatic. For developing convulsions – diazepam IV, for bradycardia or ventricular arrhythmias – atropine, lidocaine. Hemodialysis is effective.

Drug Interactions

Tobacco smoking reduces the effectiveness of ranitidine.

Increases the concentration of metoprolol in blood serum (by 80% and 50%, respectively), while the half-life of metoprolol increases from 4.4 to 6.5 hours.

Due to an increase in the pH of the stomach contents, simultaneous administration may reduce the absorption of itraconazole and ketoconazole.

Inhibits the metabolism in the liver of phenazone, aminophenazone, diazepam, hexobarbital, propranolol, diazepam, lidocaine, phenytoin, theophylline, aminophylline, indirect anticoagulants, glipizide, buformin, metronidazole, calcium antagonists.

Drugs that suppress the bone marrow increase the risk of neutropenia.

When used simultaneously with antacids, sucralfate in high doses, the absorption of ranitidine may be slowed, so the interval between taking these drugs should be at least 2 hours.

Storage Conditions

List B. Store at a temperature not exceeding 30°C (86°F) in a place protected from light. Do not freeze the solution.

Shelf Life

The shelf life of the tablets is 3 years, the solution for IM and IV administration is 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.