Comprehensive Overview of Ranitidine

Ranitidine, a histamine H2-receptor antagonist, is a pharmacological agent that inhibits gastric acid secretion by competitively blocking H2 receptors on the parietal cells of the stomach. Introduced under the brand name Zantac in the late 1970s, ranitidine rapidly gained prominence as a treatment for acid-related gastrointestinal disorders due to its improved safety and efficacy over earlier H2 antagonists like cimetidine. Although global recalls were initiated in response to contamination with N-nitrosodimethylamine (NDMA), the reformulation and reapproval of ranitidine under strict regulatory standards have reinstated its clinical relevance.

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Clinical Uses

Ranitidine is indicated for a broad range of gastrointestinal conditions linked to excessive gastric acid production. These include gastroesophageal reflux disease (GERD), peptic ulcer disease (both duodenal and gastric), Zollinger-Ellison syndrome, and non-ulcer dyspepsia. It also serves a prophylactic function in preventing stress ulcers in critically ill patients and can be used in combination regimens to eradicate Helicobacter pylori. In paediatric cases, ranitidine is prescribed for reflux oesophagitis and other hypersecretory disorders, with careful consideration of dosing parameters.

Dosage and Administration

Ranitidine is administered orally or intravenously, tailored to the patient's clinical condition. For adults, the typical oral dosage is 150 mg twice daily or a single 300 mg dose at bedtime. In hospital settings, IV dosing is usually 50 mg every 6 to 8 hours. Ranitidine can be taken with or without food; however, consistent timing supports better absorption. For children, dosing is weight-based (mg/kg), with strict adherence to maximum limits to ensure safety.

Dose Adjustment in Special Populations

Renal Impairment

As ranitidine is primarily excreted through the kidneys, dosage must be reduced in patients with renal insufficiency (creatinine clearance <50 mL/min). A 50% dose reduction or prolonged dosing intervals are typically recommended to prevent drug accumulation.

Hepatic Impairment

Although the hepatic metabolism of ranitidine is limited, patients with liver disease should be monitored closely, especially during long-term therapy, to avoid potential hepatic decompensation.

Pregnancy

Ranitidine is classified as a Category B drug during pregnancy, meaning no harm was noted in animal studies. However, due to limited human data, its use should be restricted to necessary cases. The lowest effective dose should be administered for the shortest duration possible.

Adverse Effects

Ranitidine is generally well tolerated. Common side effects include gastrointestinal disturbances such as constipation, diarrhoea, and abdominal discomfort. Neurological symptoms like headache and dizziness, as well as dermatological reactions such as rash, are also possible. Less common but more serious effects include elevated liver enzymes, cardiac arrhythmias, interstitial nephritis, and haematologic abnormalities like thrombocytopenia. Long-term acid suppression has been linked to vitamin B12 deficiency, increased susceptibility to infections such as Clostridioides difficile, and alterations in gut microbiota.

Drug Combinations and Infusion Considerations

Ranitidine is frequently used alongside other medications to improve therapeutic outcomes. It may be combined with proton pump inhibitors in resistant cases or with NSAIDs to protect the gastric lining. When administered intravenously, it must be diluted (e.g., in 20 mL of 0.9% saline) and infused over at least 5 minutes to avoid hypotension or bradycardia. Monitoring is particularly vital in elderly or haemodynamically unstable patients.

Pharmaceutical Presentations and Dosage Forms

Dosage Form	Strength	Notes
Tablets	75 mg, 150 mg, 300 mg	Oral administration for adults and teens
Oral Syrup	15 mg/mL	Suitable for paediatrics and swallowing issues
Intravenous (IV)	25 mg/mL	Used in acute care settings

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Pharmacokinetics and Pharmacodynamics

Ranitidine has a moderate oral bioavailability of approximately 50% due to first-pass hepatic metabolism. Peak plasma concentrations are reached within 1 to 3 hours, and its half-life is around 2.5 to 3 hours. The drug is largely excreted via the kidneys. Ranitidine’s mechanism of action involves reversible inhibition of H2 receptors, thereby reducing both basal and meal-stimulated gastric acid secretion. Although not antimicrobial, this effect supports mucosal healing and aids in H. pylori treatment when used with antibiotics.

Drug Interactions

Ranitidine’s suppression of gastric acid can affect the absorption of pH-sensitive drugs such as ketoconazole, itraconazole, and atazanavir. It may also alter the effects of drugs with narrow therapeutic indices, such as warfarin and theophylline, through minor alterations in hepatic enzyme activity. Alcohol metabolism may be impaired, necessitating caution due to the potential for increased systemic alcohol levels. Unlike cimetidine, ranitidine exerts minimal influence on CYP450 enzymes.

Comparison with Other H2-Receptor Antagonists

Agent	Acid Suppression Potency	Duration of Action	Adverse Effect Profile	Clinical Notes
Ranitidine	Moderate	8–12 hours	Generally well tolerated	Reformulated after NDMA concerns
Famotidine	High	10–12 hours	Excellent safety profile	Preferred first-line H2 antagonist
Cimetidine	Low	6–8 hours	Higher risk of interactions	Inhibits CYP450, extensive drug interactions

Precautions and Special Considerations

Prior to prescribing ranitidine, it is crucial to rule out malignancy in patients presenting with new or atypical gastrointestinal symptoms, as symptom relief might mask serious underlying conditions. Extended use warrants monitoring for vitamin B12 deficiency. Dosage should be cautiously adjusted in elderly patients and those with renal impairment, as they are more susceptible to central nervous system effects. Alcohol consumption should be minimised to avoid pharmacokinetic interactions.

Toxicity and Overdose Management

Overdose with ranitidine is uncommon but may present with confusion, dizziness, nausea, vomiting, and bradycardia. No specific antidote exists. Management is supportive and includes gastric lavage, activated charcoal administration, fluid resuscitation, electrolyte balance, and cardiac monitoring. Severe cases may necessitate hospitalisation for continuous observation.

Recent Updates and Guidelines (2025)

In 2025, the reintroduction of ranitidine was approved by leading regulatory bodies such as the MHRA and EMA. Reformulated versions are manufactured with stringent quality control to ensure NDMA levels are below harmful thresholds. According to updated NICE guidelines, ranitidine should only be considered when alternatives like famotidine are unavailable or contraindicated, and should be used for the shortest effective duration. Ongoing surveillance programs are in place to monitor long-term safety outcomes.