Ranitidine

Ranitidine

Overview

Ranitidine is an H2 receptor antagonist. It’s a competitive, reversible inhibitor of the action of histamine at the histamine H2-receptors, including receptors on the gastric cells. Ranitidine does not lower serum Ca++ in hypercalcemic states. Also, it is not an anticholinergic agent.

Uses

  • Short-term treatment of active duodenal ulcer. Most patients heal within 4 weeks. Studies available to date have not assessed the safety of ranitidine in uncomplicated duodenal ulcer for periods of more than 8 weeks.
  • Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers. No placebo-controlled comparative studies have been carried out for periods of longer than 1 year.
  • The treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome and systemic mastocytosis).
  • Short-term treatment of active, benign gastric ulcer. Most patients heal within 6 weeks and the usefulness of further treatment has not been demonstrated. Studies available to date have not assessed the safety of ranitidine in uncomplicated, benign gastric ulcer for periods of more than 6 weeks.
  • Maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers. Placebo-controlled studies have been carried out for 1 year.
  • Treatment of GERD.
  • Treatment of endoscopically diagnosed erosive esophagitis.
  • Maintenance of healing of erosive esophagitis. Placebo-controlled trials have been carried out for 48 weeks.

Pharmacological Classification

H2 blocker.

Brand names

Zantac, Zantac 25, Zantac 150, Zantac 300

Dosage form

Tablets: Zantac 150, Zantac 300

Effervescent tablets: Zantac 25

Syrup: Zantac

Mechanism of Action

Ranitidine is a competitive inhibitor of histamine at the parietal cell H2 receptor. It suppresses the normal secretion of acid by parietal cells as well as the meal-stimulated acid secretion by parietal cells. This is achieved by two mechanisms:

  • Histamine, which is released by ECL cells in the stomach, is blocked from binding with H2 receptors on parietal cell, which stimulates acid secretion.
  • When the H2 receptors are blocked, substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells.

Dosage & Administration

Adult Dose

For the treatment of active duodenal ulcers

  • Tablets:
    • 1 tablet of Zantac 150 twice a day.
    • An alternative dose of 1 tablet of Zantac 300 tablet once a day after the evening meal or at bedtime can be used for patients in whom dosing convenience is important.
  • Syrup:
    • 10 ml (2 teaspoonfuls) of Zantac syrup twice a day. This (10 ml) is equivalent to Ranitidine 150 mg.
    • An alternative dose of 20 ml (4 teaspoonfuls) of Zantac syrup once a day after the evening meal or at bedtime can be used for patients in whom dosing convenience is important.

Note: In a clinical trials conducted in the US on atients suffering from active duodenal ulcers, it has been found that smaller doses are equally effective in inhibiting gastric acid secretions. Several other trials conducted in foreign countires also suggest that a dose of 100 mg twice a day is equally efficacious to a dose of 150 mg.

Maintenance of Healing of Duodenal Ulcers

  • Tablets:
    • 1 tablet of Zantac 150 once a day at bedtime.
  • Syrup:
    • 10 ml (2 teaspoonfuls) of Zantac syrup once a day at bedtime. This (10 ml) is equivalent to Ranitidine 150 mg.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome)

  • Tablets:
    • 1 tablet of Zantac 150 twice a day.
  • Syrup:
    • 10 ml (2 teaspoonfuls) of Zantac syrup twice a day. This (10 ml) is equivalent to Ranitidine 150 mg.

In some patients, frequent administration of Zantac 150 mg doses may be necessary. However, dosage should be adjusted according to individual patient’s need and it should be continued as long as clinically indicated. Dosages up to 6 g/day have been employed in patients with severe disease.

Benign Gastric Ulcer

  • Tablets:
    • 1 tablet of Zantac 150 twice a day.
  • Syrup:
    • 10 ml (2 teaspoonfuls) of Zantac syrup twice a day. This (10 ml) is equivalent to Ranitidine 150 mg.

Maintenance of Healing of Gastric Ulcers

  • Tablets:
    • 1 tablet of Zantac 150 once a day at bedtime.
  • Syrup:
    • 10 ml (2 teaspoonfuls) of Zantac syrup once a day at bedtime. This (10 ml) is equivalent to Ranitidine 150 mg.

GERD

  • Tablets:
    • 1 tablet of Zantac 150 twice a day.
  • Syrup:
    • 10 ml (2 teaspoonfuls) of Zantac syrup twice a day. This (10 ml) is equivalent to Ranitidine 150 mg.

Erosive Esophagitis

  • Tablets:
    • 1 tablet of Zantac 150 4 times a day.
  • Syrup:
    • 10 ml (2 teaspoonfuls) of Zantac syrup 4 times a day. This (10 ml) is equivalent to Ranitidine 150 mg.

Maintenance of Healing of Erosive Esophagitis

  • Tablets:
    • 1 tablet of Zantac 150 twice a day.
  • Syrup:
    • 10 ml (2 teaspoonfuls) of Zantac syrup twice a day. This (10 ml) is equivalent to Ranitidine 150 mg.

Pediatric Dose

Note: The safety and efficacy of Ranitidine (Zantac) has been established in the age-group of 1 month to 16 years.

Treatment of Duodenal and Gastric Ulcers

  • The recommended oral dose for the treatment is 2 to 4 mg/kg twice a day to a maximum of 300 mg/day.

Maintenance of Healing of Duodenal and Gastric Ulcers

  • The recommended oral dose for the maintenance is 2 to 4 mg/kg twice a day to a maximum of 150 mg/day.

Treatment of GERD and Erosive Esophagitis

  • Limited data exist for these conditions in pediatric conditions.
  • A dosage of 5 to 10 mg/kg per day, usually given as 2 divided doses.

Renal Dose Adjustment

Patients with severely impaired renal function with a creatinine clearance <50 mL/min

  • 150 mg tablet or 10 ml of syrup (2 teaspoonfuls) every 24 hours.
  • If required, the dosing frequency may be increased to every 12 hours or even further, but with caution.
  • Since hemodialysis reduces the level of circulating ranitidine, the dosing schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.

Elderly Dose Adjustment

  • Elderly patients are more likely to have decreased renal function. Hence caution should be exercised in dose selection, and it may be useful to monitor renal function.

Overdosage

  • Limited data available on overdose.
  • Side effects observed or experienced in an event of overdose are similar to the ones experienced under normal dosage conditions.
  • Abnormalities on gait and hypotension have been reported.
  • When overdosage occurs, the usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.
  • Haemodialysis reduces the level of circulating ranitidine.

Side Effects or Unwanted Effects

Headache – mild to severe.

CNS (Central nervous System) Side effects

  • Malaise
  • Dizziness
  • Somnolence
  • Insomnia
  • Vertigo
  • In severely ill elderly patients, rare cases of reversible mental confusion, agitation, depression, and hallucinations have been reported.
  • Rare cases of reversible blurred vision suggestive of a change in accommodation have been reported.
  • Rare reports of reversible involuntary motor disturbances have been received.

Cardiovascular Side effects

Just like with other H2 blockers, occurrences of below-mentioned arrhythmias have been rarely reported.

  • Tachcardia
  • Bradycardia
  • Atrioventricular block
  • Premature ventricular beats

Gastrointestinal Side Effects

  • Diarrhea
  • Constipation
  • Nausea and Vomitting
  • Abdominal discomfort or pain
  • Pancreatitis (Rarely reported)

Hepatic Side Effects

  • Reports of occasional occurrence of hepatocellular, cholestatic, or mixed hepatitis with or without jaundice. Ranitidine should be immediately discontinued.
    • These events are usually reversible but in rare cases, death has occurred.
  • Rare cases of hepatic failure has also been reported.

Musculoskeletal Side Effects

  • Arthralgia
  • Myalgia

Hematologic Side Effects

  • Reversible side effects
    • Leukopenia
    • Granulocytopenia
    • Thrombocytopenia
  • Rare occurrences of:
    • Agranulocytosis
    • Pancytopenia
    • Marrow hypoplasia
    • Aplastic anemia
  • Exceedingly rare cases of:
    • Acquired immune hemolytic anemia

Endocrine Side Effects

  • Occasional occurrences of:
    • Gynecomastia
    • Impotence
    • Loss of libido
  • No stimulation of any pituitary hormone
  • No antiandrogenic activity
  • Cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when Ranitidine has been substituted.

Integumentary Side Effects

  • Rash
  • Rare occurrences of:
    • Erythema multiforme
    • Alopecia
    • Vasculitis

Other Side Effects

  • Rare cases of
    • Hypersensitivity reactions like:
      • Bronchospasm
      • Fever
      • Rash
      • Eosinophilia
    • Anaphylaxis
    • Angioneurotic edema
    • Small increases in serum creatinine

Warnings & Precautions

  • Symptomatic response to therapy with Ranitidine does not preclude the presence of gastric malignancy.
  • Since Ranitidine is excreted primarily by the kidney, dosage should be adjusted in patients with impaired renal function.
  • Caution should be observed in patients with hepatic dysfunction since Ranitidine is metabolized in the liver.
  • Rare reports suggest that Ranitidine may precipitate acute porphyric attacks in patients with acute porphyria. Ranitidine should, therefore, be avoided in patients with a history of acute porphyria.
  • Information for Patients: Phenylketonurics: ZANTAC 25 EFFERdose Tablets contain phenylalanine 2.81 mg per 25 mg of ranitidine. ZANTAC 150 EFFERdose Tablets contain phenylalanine 16.84 mg per 150 mg of ranitidine. ZANTAC EFFERdose Tablets should not be chewed, swallowed whole, or dissolved on the tongue.

Contraindications

  • Ranitidine is contraindicated in patients known to have hypersensitivity to the drug or any of the ingredients of the formulation.

Pregnancy

Category B, which means that Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Nursing Mothers

  • Ranitidine is secreted in mother’s milk.
  • Caution should be exercised when Ranitidine is administered to a nursing mother.

Interactions

Drug-drug interactions

  • Acalabrutinib: Ranitidine reduces the level of acidity in the stomach which may interfere with the absorption of Acalabrutinib.
    • In order to prevent this, Acalabrutinib should be taken at least 2 hours before Ranitidine.
  • Acetohexamide: Concomitant use of Acetohexamide with Ranitidine may increase the effects of Acetohexamide, which may cause a person’s blood pressure to get too low.
    • Talk to your doctor if you are taking these medications. This may require dose adjustments of either 1 or both of these medicines. Your doctor may ask you to get some tests done before making any changes in the dosage.
  • Adefovir: Concomitant use of Adefovir and Ranitidine may increase the blood levels or side effects of any 1 or both the medicines.
    • Talk to your doctor if you are taking these medications. This may require dose adjustments of either 1 or both of these medicines. Your doctor may ask you to get some tests done before making any changes in the dosage.
  • Aminophylline: Ranitidine may increase the effects of Aminophylline.
    • Concomitant use of Ranitidine and Aminophylline may require dose adjustment.
  • Atazanavir, Dabrafenib, Delavirdine, Donepezil: Ranitidine may reduce the effectiveness of these medicines.
  • Bacampicillin: Ranitidine may decrease the absorption and blood levels of Bacampicillin and hence reduces the effectiveness of bacampicillin.
  • Tenofovir: Ranitidine may increase the blood levels and effects of both the medicines.
  • Bosutinib: Ranitidine reduces the levels of acid in the stomach, which may interfere with the absorption of Bosutinib and reduce its effectiveness.
  • Brigatinib: Ranitidine and Brigatinib may have an additive effect in lowering the heart rate.
  • Metformin: Concomitant use of Metformin and Ranitidine may increase the effects of
    Metformin , which may lead to a life-threatening condition called lactic acidosis.
  • Cefditoren, Cefpodoxime, Cefuroxime, Ceritinib: Ranitidine reduces the levels of acidity in the stomach which may decrease the absorption of these medicines, making them less effective.
  • Quinidine: Ranitidine can increase the effects of Quinidine.