Ranitidine Hydrochloride

Ranitidine Hydrochloride

75mg Tablet

150mg Tablet

300mg Tablet

Drug Category: H₂ Receptor Antagonist

Structure and Chemical Name:

N[2-[[[5-[9dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N-methyl-2-nitro-1,1-ethenediamine, hydrochloride. C₁₃H₂₂N₄S.HCl

Pharmacology:

Ranitidine is a specific rapidly acting histamine H₂-antagonist. It inhibits basal and stimulated secretions of gastric acid, reducing both the volume and the acid and pepsin content of the secretion. Ranitidine has a long duration of action and a single 75-mg dose suppresses gastric acid secretion for up to twelve hours.

Clinical studies have shown that Ranitidine can relieve the symptoms of excess acid production for up to twelve hours.

Pharmacokinetics:

Ranitidine HCl is 50% absorbed after oral administration. Absorption is not significantly impaired by the administration of food or antacids. Following a single dose of 150mg, serum concentrations of ranitidine HCl are in this range up to 12 hours. However, blood levels bear no consistent relationship to dose or degree of acid inhibition.

The principal route of excretion is the urine, with approximately 30% of the orally administered dose collected in the urine as unchanged drug in 24 hours. Renal clearance is about 410ml per minute, indicating active tubular excretion.

In man, the N-oxide is the principal metabolite in he urine; however, this amounts to <4% of the dose. Other metabolites are the S-oxide (1%) and the desmethyl ranitidine (1%). The remainder of the administered dose is found in the stool.

The volume of distribution is about 1.4L/kg. Serum protein binding averages 15%.

Indications:

• Short-term treatments of active duodenal ulcer
• Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers
• The treatment of pathological hypersectory conditions (e.g. Zollinger-Ellison syndrome and systemic mastocytosis)
• Short-term treatment of active, benign gastric ulcer
• Maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers
• Treatment of GERD
• Treatment of endoscopically diagnosed erosive esophagitis
• Maintenance of healing of erosive esophagitis

Contraindications:

Ranitidine is contraindicated for patients known to be hypersensitivity to the drug or any of the ingredients of the product.

Precautions and Warnings:

• Ranitidine excreted via the kidney and so plasma levels of the drug are increased in patients with severe renal impairment. Ranitidine is not suitable for these patients.
• Patients who are taking non-steroidal anti-inflammatory drugs especially in the elderly should be referred to their doctor before taking ranitidine.
• Although clinical reports of acute intermittent porphyria associated with ranitidine administration have been rare and inconclusive; ranitidine should be avoided in patients with a history of this conditions.
• Treatment with histamine H₂-antagonist may mask symptoms associated with carcinoma of the stomach and may therefore delay diagnosis of the condition.

Use in Pregnancy and Lactation:

Ranitidine crosses the placenta but therapeutic doses administered to obstetric patients in labor or undergoing cesarean section have been without any adverse effect in labor, delivery or subsequent neonatal progress. Therefore, ranitidine should not be taken during pregnancy without consulting a doctor.

Ranitidine is also excreted in human breast milk and women who are breast feeding will be advised to speak to their doctor before taking Ranitidine.

Drug Interactions:

• Although ranitidine has been reported to bind weakly to cytochrome P-450 in vitro, recommended doses of the drug do not inhibit the action of the cytochrome P-450-linked oxygenase enzymes in the liver. However, ranitidine may affect the bioavailability of certain drugs by some mechanism.
• Increased or decreased prothrombin times have been reported during concurrent use of ranitidine and warfarin. However, in human pharmacokinetic studies with dosages of ranitidine up to 400mg per day, no interaction occurred; ranitidine had no effect on warfarin clearance or prothrombin time.
• Reduced gastric acidity due to ranitidine may result in an increase in the availability of triazolam, when used concurrently. The clinical significance of triazolam and ranitidine pharmacokinetic interaction is unknown.

Adverse Effects:

• Transient and reversible changes in liver function tests can occur. There have been occasional reports of reversible hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice.
• Leucopenia and thrombocytopenia have occurred rarely in patients. The are usually reversible.
• Rare cases of agranulocytosis or of pancytopenia, sometimes with marrow hypoplasia, or aplasia have been reported.
• Hypersensitivity reactions (urticaria, angioneurotic edema, fever, bronchospasm, hypotension, anaphylactic shock) have been seen rarely following oral administration of ranitidine. These reactions have occasionally occurred after a single dose.
• As with other H₂ receptor antagonist there have been rare reports of bradycardia and AV block.
• Headache, sometimes severe and dizziness have been reported in a very small proportion of patients. Rare cases of vasculitis and alopecia have been reported rarely.
• Reversible impotence has been reported rarely.
• Musculoskeletal symptoms such as arthralgia and myalgia have been reported rarely.
• There have been a few reports of breast symptoms (swelling and/or discomfort) in men taking ranitidine; some cases have resolved on continued ranitidine treatment.

Dosage and Administration:

Usual dosage of Ranitidine is 150mg twice daily. Alternatively, it can be given as a single bedtime dose of 300mg. Treatment should be continued for up to 4-8 weeks in most cases of duodenal ulcer, gastric ulcer and post operative ulcer and reflux esophagitis. In cases of NSAIDs induced ulceration, 150mg twice daily at bedtime should be given. In patient with Zollinger-Ellison syndrome, the starting dose is 150m twice or three times daily and this may be increased as necessary. Patients with this syndrome have been given increasing doses up to 6g/day and these doses have been well tolerated; or as prescribed by the physician.

Overdosage:

Ranitidine is very specific in action and accordingly no particular problems are expected following overdosage with the drug. Symptomatic and supportive therapy should be given as appropriate. However, in case of overdose, symptomatic treatment with gastric lavage should employed. If need be, the drug may be removed form the plasma by hemodialysis.

Storage Condition:

Store at temperatures not exceeding 30^oC.

Protect from direct sunlight.

Keep out or reach of children.