Peptil H

Approved Indications (before withdrawal in many countries):

• Duodenal Ulcer:
• Short-term treatment of active duodenal ulcers.
• Maintenance therapy to prevent recurrence.
• Gastric Ulcer:
• Short-term treatment of benign gastric ulcers.
• Maintenance therapy for healed ulcers.
• Gastroesophageal Reflux Disease (GERD):
• Treatment of erosive esophagitis and symptomatic relief of GERD.
• Zollinger-Ellison Syndrome:
• Management of pathological hypersecretory conditions.
• Prevention of Stress Ulcers:
• In critically ill hospitalized patients.
• Prevention and Treatment of NSAID-induced Ulcers:
• When NSAID use is necessary.
• Heartburn and Acid Indigestion (OTC use):
• Relief and prevention of acid-related symptoms.

Clinically Accepted Off-Label Uses:

• Pediatric GERD and Ulcers:
• Short-term use in infants and children under specialist supervision.
• Anaphylaxis Adjunct:
• Used with H1-antihistamines to reduce histamine effects.

Adults:

• Duodenal/Gastric Ulcers:
  150 mg orally twice daily or 300 mg once daily at bedtime.
  Maintenance: 150 mg once daily at bedtime.
• GERD and Erosive Esophagitis:
  150 mg twice daily for 8–12 weeks.
• Zollinger-Ellison Syndrome:
  Initial: 150 mg orally three times daily; may increase up to 6 g/day.
• OTC Heartburn Relief:
  75–150 mg once or twice daily, 30–60 minutes before eating.

Pediatrics:

• GERD/Ulcers:
  2–4 mg/kg/dose orally every 8–12 hours.
  Maximum: 300 mg/day.

Elderly:

• Use lower end of dosing range due to potential for decreased renal function.

Renal Impairment:

• Creatinine clearance <50 mL/min:
  Reduce dose to 150 mg once daily.

Hepatic Impairment:

• Generally well tolerated but caution advised; monitor liver enzymes.

Route of Administration:

• Oral (tablets/syrup), IV, or IM.

Ranitidine is a selective histamine H₂-receptor antagonist that competitively inhibits histamine binding on gastric parietal cells, thereby suppressing basal and stimulated gastric acid secretion. By reducing both the volume and concentration of gastric acid, it promotes ulcer healing, decreases gastric irritation, and relieves acid-related symptoms in GERD and peptic ulcer disease. It does not affect acetylcholine or gastrin-induced acid secretion directly.

• Absorption:
  Rapid and well-absorbed orally; peak plasma levels in 1–3 hours.
• Bioavailability:
  Approximately 50% (due to first-pass metabolism).
• Distribution:
  Widely distributed; ~15% plasma protein binding.
• Metabolism:
  Partially hepatic (N-oxide, S-oxide, desmethyl ranitidine).
• Half-life:
  2–3 hours (prolonged in renal dysfunction).
• Excretion:
  Primarily via kidneys (30%–70% unchanged); some fecal elimination.

• Pregnancy:
  FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk. Use only if clearly needed.
• Lactation:
  Ranitidine is excreted into breast milk in small amounts. No known adverse effects in nursing infants, but caution is advised during prolonged use.

• Primary Class: H₂-Receptor Antagonist (H₂ Blocker)
• Subclass: Second-generation acid-reducing agent

• Known hypersensitivity to ranitidine or any formulation component
• History of acute porphyria (ranitidine may trigger attacks)
• Use in patients with confirmed gastric malignancy (may mask symptoms)

• Carcinogenic Impurities:
  Detection of NDMA (N-nitrosodimethylamine), a probable human carcinogen, led to worldwide withdrawal/suspension.
• Masking of Malignancy:
  Symptom relief may delay gastric cancer diagnosis. Evaluate unexplained weight loss or persistent symptoms.
• Hepatic Effects:
  Rare cases of hepatitis and liver enzyme abnormalities reported.
• Renal Impairment:
  Accumulation may increase CNS adverse effects (e.g., confusion in elderly).
• Bradycardia (IV use):
  Reported with rapid IV administration.

Common:

• Headache
• Diarrhea or constipation
• Abdominal discomfort
• Dizziness

Less Common:

• Rash
• Nausea or vomiting
• Elevated liver enzymes

Serious (Rare):

• Hepatitis, cholestatic jaundice
• Blood dyscrasias (thrombocytopenia, neutropenia)
• CNS effects (confusion, hallucinations—especially in elderly)
• Anaphylaxis or bronchospasm

Onset:

• Typically occurs within hours to days of initiation. CNS side effects more common in high doses or renal failure.

• Ketoconazole, Itraconazole:
  Reduced absorption due to decreased gastric acidity.
• Atazanavir, Delavirdine:
  Decreased plasma concentrations (acid-dependent absorption).
• Warfarin:
  Increased anticoagulant effect (monitor INR).
• Procainamide, N-acetylprocainamide:
  Increased levels in renal dysfunction.
• No CYP450 inhibition, but alters absorption of drugs dependent on gastric pH.

• FDA Update (April 2020):
  All ranitidine products were removed from the U.S. market due to unacceptable NDMA levels over time and temperature.
• EMA & WHO Statements:
  Advised discontinuation and replacement with alternative H₂ blockers or PPIs.
• Guideline Adjustments:
  Clinical guidelines now favor famotidine or PPIs (e.g., omeprazole) for acid suppression due to safety concerns.

• Temperature:
  Store at 20°C to 25°C (68°F to 77°F).
  Excursions permitted to 15°C–30°C.
• Humidity/Light:
  Protect from excessive moisture. Store in a tightly closed container.
• Handling:
  Protect from freezing. Do not expose to heat sources that may accelerate NDMA formation.
• IV Solutions:
  Reconstituted solutions are stable for 48 hours under refrigeration.