Zantac

Drugs , Gastrointestinal System / November 4, 2016

Class: Gastrointestinal System
Dosage Form: Various
Description: H2-receptor antagonist for treatment of peptic ulcer
Stock: Available
Manufacturer: GlaxoSmithKline (GSK)

Composition:

Tablets:
Ranitidine (as the hydrochloride)…………150 or 300 mg
Effervescent Tablets:
Ranitidine (as the hydrochloride)……………………150 mg
Ampoules:
Ranitidine (as the hydrochloride)…………..50 mg in 2ml

Properties:

Pharmacodynamics
Ranitidine is a specific histaime H2-antagonist. It inhibits basal and stimulated secretions of gastric acid, reducing both the volume and the acid and pepsin content of the secretion.

Pharmacokinetics
a) Oral Formulation:
Ranitidine has a relatively long duration of action and so a single 150 mg dose effectively suppresses gastric acid secretion for 12 hours. Clinical evidence has shown that ranitidine combined with amoxycillin and metronidazole eradicates Helicobacter pylori in approximately 90% of patients. This combination therapy has been shown to significantly reduce duodenal ulcer recurrence. Helicobacter pylori infects about 95% of patients with duodenal ulcer and 80% of patients with gastric ulcer.
b) Injection:
Absorption of ranitidine after IM injection is rapid and peak plasma concentrations are usually achieved within 15 min of administration.

Indications:

1.Oral Formulation:

  • Duodenal ulcer and benign gastric ulcer, including that associated with non-steroidal anti-inflammatory agents
  • Prevention of non-steroidal anti-inflammatory drug (including aspirin) associated duodenal ulcers, especially in patients with ah history of peptic ulcer disease
  • Chronic episode dyspepsia, characterized by pain (epigastirc or retrosternal) which is related to meals or disturbs sleep but not associated with the above conditions
  • Duodenal ulcer associated with Helicobacter pylori infection
  • Post-operative ulcer and reflux esophagitis
  • Symptom relief in gastro-oesophageal reflux disease
  • Zollinger-Ellison syndrome
  • Prophylaxis of stress ulceration in seriously ill patients
  • Prophylaxis of recurrent haemorrhage from peptic ulcer

2. Injection:

  • Duodenal ulcer; benign gastric ulcer; post-operative ulcer; and reflux esphagitis
  • Zollinger-Ellison syndrome
  • Prophylaxis of stress ulceration in seriously ill
  • Prophylaxis of recurrent haemorrhage from peptic ulcer
  • Prophylaxis of Mendelson’s syndrome

Contraindicatons:

Ranitidine products are contraindicated in patients known to have hypersensitivity to any component of the preparation.

Drug Interactions:

Ranitidine, at blood levels produced by standard recommended doses, does not inhibit the hepatic cytochrome P450-linked mixed function oxygenase system. Accordingly, ranitidine in usual therapeutic doses does not potentiate the actions of drugs which are inactivated by this enzyme; these include diazepam, lignocaine, phenytoin, propanolol, theophylline and warfarin.
There is no evidence of interaction between ranitidine and amoxycillin and metronidazole.
If high doses (2 g) of sucralfate are co-administered with ranitidine, the absorption of the latter may be reduced. This effect is not seen if sucralfate is taken after an interval of 2 hours.

Side Effects:

The following convention has been utilised for the classification of undesirable effects; very common (>1/10), common (>1/100), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/10,000). Adverse event frequencies have been estimiated from spontaneous reports from post-marketing data.
1. Blood and lymphatic System Disorders:

  • Very rare: Blood count changes (leucopenia, thrombocytopoenia). These are usually reversible. Agranulocytosis or pancytopoenia, sometimes with marrow hypoplasia or marrow aplasia.

2. Immune System Disorders:

  • Rare: Hypersensitivity reactions (urticaria, angioneurotic oedema, fever, bronchospasm, hypotension and chest pain)
  • Very rare: Anaphylactic shock. These events have been reported after a single dose.

3. Psychiatrist Disorders:

  • Very rare: Reversible mental confusion, depression and hallucinations These have been reported predominantly in severely ill and elderly patients.

4. Nervous System Disorders:

  • Very rare: Headache (sometimes severe), dizziness and reversible-involuntary movement disorders

5. Eye Disorders:

  • Very rare: Reversible blurred vision There have been reports of blurred vision, which is suggestive of a change in accommodation.

6. Cardiac Disorders:

  • Very rare: As with other H2-receptor antagonists bradycardia, AV block and asystole (injection only)

7. Vascular Disorders:

  • Very rare: Vasculitis

8. Gastrointestinal Disorders:

  • Very rare: Acute pancreatitis, diarrhoea

9. Hepatobiliary Disorders:

  • Rare: Transient and reversible changes in liver function tests
  • Very rare: Hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice. These were usually reversible.

10. Skin and Subcutaneous Tissue Disorders:

  • Rare: Skin rash
  • Very rare: Erythema multiforme, alopecia

11. Musculoskeletal and Connective Tissue Disorders:

  • Very rare: Musculoskeletal symptoms such as arthralgia and myalgia

12. Renal and Urinary Disorders:

  • Very rare: Acute intestinal nephritis

13. Reproductive System and Breast Disorders:

  • Very rare: Reversible impotence, breast symptoms in men

Dosage and Administration:

1. Oral Formulations:
a) Duodenal ulcer and benign gastric ulcer:

  • Acute treatment: The standard dosage regimen for duodenal or bening gastric ulcer is 150 mg twice daily or 300 mg nocte. In most cases of duodenal ulcer or benign gastric ulcer, healing occurs within one four weeks. Healing usually occurs after a further four weeks in those not fully healed after the initial four weeks.
  • Long-term management: For the long-term management of duodenal or benign gastric ulcer the usual dosage regimen is 150 mg nocte. Smoking is associated with a higher rate of duodenal ulcer relapse, and such patients should be advised to stop smoking. In those who fail to comply with such advice a dose of 300 mg nocturnally provides additional therapeutic benefit over the 150 mg dosage regimen.

b) NSAID associated peptic ulcer:

  • Acute treatment: In ulcers following non-steroidal anti-inflammatory drug therapy, or associated with continued non-steroidal anti-inflammatory drugs, 8 to 12 weeks treatment may be necessary with 150 mg twice daily or 300 mg nocte
  • Prophylaxis: For the prevention of non-steroidal anti-inflammatory drug-associated duodenal ulcers, ranitidine 150 mg twice daily may be given concomitantly with non-steroidal anti-inflammatory drug therapy

c) Duodenal ulcer associated with Helicobacter pylori infection:

  • Ranitidine 300 mg at bedtime or 150 mg twice daily may be given with oral amoxycillin 750 mg three times daily and metronidazole 500 mg three times daily for two weeks.
  • Therapy with ranitidine only should continue for a further two weeks. This dose regiment significantly reduces the frequency of duodenal ulcer recurrence.

d) Post-operative ulcer:

  • The standard dosage regimen for post-operative ulcer is 150 mg twice daily. most cases heal within four weeks
  • Those not fully healed after the intial four weeks usually do so after a further four weeks

e) Gastro-oesophageal reflux disease:

  • Acute reflux oesophagitis: In reflux oesophagitis 150 mg twice daily or 300 mg nocte is administered for up to a period of 8, or if necessary, 12 weeks. In patients with moderate-to-severe oesophagitis, the dosage of ranitidine may be increased to 150 mg four times daily for up to 12 weeks
  • Long-term management of reflux oesophagitis: For the long-term management of reflux oesophagitis, the recommended adult oral dose is 150 mg twice daily
  • Symptom relief: For the relief of symptoms associated with esophageal acid reflux, the recommended regimen is 150 mg twice daily for two weeks. This regimen may be continued for a further two weeks in those patients in whom the initial response is inadequate.

f) Zollinger-Ellison syndrome:

  • The initial dosage regimen is 150 mg three times daily, but this may be increased as necessary
  • Doses up to 6 g per day have been well tolerated

g) Chronic episodic dyspepsia:

  • The standard dosage regimen is 150 mg twice daily for up to 6 weeks. Anyone not responding or relapsing shortly afterwards should be investigated

h) Prophylaxis of Mendelson’s syndrome:

  • 150 mg 2 hours before anesthesia, and preferably 150 mg the previous evening
  • Alternatively, the injection is also available
  • In obstetric patients in labour, 150 mg every 6 hours, but if general anesthesia is required it is recommended that a non-particulate antacid (e.g. sodium citrate) be given in addition

i) Prophylaxis of haemorrhage from stress ulceration in seriously ill patients or prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration:

  • 150 mg twice daily may be substituted from the injection once oral feeling commences

2. Injection:
a) Ranitidine injection may be given as:

  • IV injection of 50 mg, diluted to a volume of 20 ml, every 6 to 8 hours
  • An intermittend IV infusion at 25 mg/h for 2 hours, repeated at 6 to 8 hour intervals
  • An IM injection of 50 mg every 6 to 8 hours

b) Prophylaxis of Mendelson’s syndrome:

  • For prophylaxis of Mendelsons’s snydrome, 50 mg by IM or slow IV injection 45 to 60 minutes before induction of general anesthesia

c) Prophylaxis of haemorrhage from stress ulceration in seriously ill patients or prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration:

  • In the prophylaxis of haemorrhage from stress ulceration in seriously ill patients or prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration, parenteral administration may be continued until oral feeding commences
  • Patients considered to be still at risk may then be treated with ranitidine tablets 150 mg twice daily
  • In the prophylaxis of upper gastrointestinal haemorrhage from stress ulceration in seriously ill patients, a priming dose of 50 mg as a slow IV injection followed by a continuous intravenous infusion of 0.125-0.250 mg/kg/h may be preferred

3. Use in Children:
a) Oral formulations:

  • The recommended oral dose for the treatment of peptic ulcer in children is 2 mg/kg up to 4 mg/kg twice daily to a maximum of 300 mg ranitidine per day

b) Injection:

  • Use in children has not been evaluated

4. Use in Renal Impairment:
a) Oral formulations:

  • Accumulation of ranitidine with resulting elevated plasma concentrations will occur in patients with severe renal impairment (creatinine clearance less than 50 ml/min)
  • It is recommended that the daily dose of ranitidine in such patients should be 150 mg
  • In patient undergoing chronic ambulatory peritoneal dialysis or chronic haemodialysis, ranitidine (150 mg) should be taken immediately after dialysis

b) Injection:

  • Accumulation of ranitidine with resulting elevated plasma concentrations will occur in patients with severe renal impairment (creatinine clearance less than 50 ml/min)
  • It is recommended in such patients that ranitidine be administered in doses of 25 mg

Overdosage:

Ranitidine is very specific in action and no particular problems are expected following overdosage with ranitidine formulatios.
Effervescent Tablets: Clinicians should be aware of the sodium content treatment.
Symptomatic and supportive therapy should be given as appropriate. If need be, the drug may be removed from the plasma by haemodialysis.

Pregnancy and Lactation:

Pregnancy
Ranitidine crosses the placenta. Like other drugs, ranitidine should only be used during pregnancy if considered essential.
Lactation
Ranitidine is excreted in human breast milk. Like other drugs, ranitidine should only be used during nursing if considered essential.

Warnings:

The possibility of malignancy should be excluded before commencement of therapy in patients with gastric ulcer (and if indications include dyspepsia; patients of middle age and over, with new or recently charged dyspeptic symptoms must be included) as treatment with ranitidine may mask symptoms of gastric carcinoma.
Ranitidine is excreted via the kidneys and so plasma levels of the drug are increased in patients with severe renal impairment.
The dosage should be adjusted as detailed above under ‘Dosage and Administration in Renal Impairment’.
Rare clinical reports suggest that ranitidine may precipitate acute prophyric attacks. Ranitidine should therefore be avoided in patients with a history of acute porphyria.
1. Oral formulations only:
Regular supervision of patients who are taking non-steroidal anti-inflammatory drugs concomitantly with ranitidine is recommended, especially in the elderly and in those with a history of peptic ulcer.

2. Effervescent tablets:
Ranitidine effervescent tablets/granules contain sodium (see excipients for sodium content). Care should therefore be taken in treating patients in whom sodium restriction is indicated.

3. Injection:
Bradycardia in association with rapid administration of ranitidine injection has been reported rarely, usually in patients with factors predisposing to cardiac rhythm disturbances. Recommended rates of administration should not be exceeded. The use of higher than recommended doses of IV H2-antagonists has been associated with rises in liver enzymes when treatment has been extended beyond five days.

Packaging:

Pack of 2 strips of 10 tablets each.
2 aluminum cylinders of 10 effervescent tablets each.
Pack of 5 ampoules of 2 ml each.

Storage:

Store at room temperature, below 25°C.

No Comments

Leave a Reply

%d bloggers like this:
Skip to toolbar