RECIM-200 TABLETS

Indications

• Benign gastric ulceration
• Benign duodenal ulceration
• Gastroesophageal reflux disease
• Pathological hypersecretion conditions
• NSAID-associated ulceration
• Prophylaxis of stress ulceration

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidance.

Adults: 400 mg twice daily, adjusted according to response, to be taken with breakfast and at bedtime. For NSAID-associated ulceration, 400 mg twice daily for 8 weeks, to be taken with breakfast and at night.

Mechanism of action

Cimetidine binds to H2-receptors located on the basolateral membrane of gastric parietal cells, competitively inhibiting histamine's effects. This leads to reduced gastric acid secretion and a decrease in gastric volume and acidity. The drug also inhibits acid secretion stimulated by gastrin and, to a lesser extent, muscarinic agonists. It affects both basal and nocturnal acid secretion as well as secretion triggered by food and other pharmacological agents.

Pharmacodynamics

Cimetidine significantly reduces basal and nocturnal gastric acid secretion, as well as the volume and acidity of gastric juice. It treats gastrointestinal disorders like gastric and duodenal ulcers, gastroesophageal reflux disease, and hypersecretory conditions. It also inhibits various isoenzymes of the hepatic CYP450 system and can increase the gastric bacterial flora.

Pharmacokinetics

Cimetidine is absorbed through the gastrointestinal tract, with peak plasma concentrations typically occurring within 1-2 hours after oral administration. It undergoes hepatic metabolism and is excreted primarily in urine. The drug's half-life is approximately 2 hours, but it may be prolonged in cases of renal impairment. Dose adjustments are necessary for patients with reduced renal function.

Adverse effects

• Anaphylactic reaction
• Aplastic anaemia
• Confusion
• Depression
• Erectile dysfunction
• Gynaecomastia
• Hallucination
• Hepatic disorders
• Leucopenia
• Nausea
• Tachycardia
• Agranulocytosis
• Alopecia
• Arthralgia
• Fever
• Galactorrhoea
• Pancytopenia
• Thrombocytopenia
• Vasculitis

Interactions

• Cimetidine + anthracyclines: Severe (increases exposure)
• Cimetidine + epirubicin: Severe (increases exposure)
• Cimetidine + fampridine: Severe (increases concentration)
• Cimetidine + aminophylline: Moderate (increases concentration)
• Cimetidine + flecainide: Moderate (increases exposure)
• Cimetidine + lidocaine: Moderate (increases exposure)
• Cimetidine + propafenone: Moderate (increases exposure)
• Cimetidine transiently + antiepileptics: Moderate (increases concentration)
• Cimetidine transiently + carbamazepine: Moderate (increases concentration)
• Cimetidine + antiepileptics: Moderate (increases concentration)

Precautions

• Caution in patients with signs and symptoms of gastric cancer
• Caution in hepatic impairment (increased risk of confusion)
• Caution in renal impairment (dose adjustments required)
• Monitor for confusion or depressive symptoms

Pregnancy

Cimetidine should be used during pregnancy only if clearly needed. There are no adequate and well-controlled studies in pregnant women.

Breast-feeding

Significant amounts are present in breast milk. While not known to be harmful, the manufacturer advises caution.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Cimetidine 200 mg tablets
• Cimetidine 400 mg tablets

Mechanism of action

Cimetidine binds to an H₂-receptor located on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity. H2 antagonists inhibit gastric acid secretion elicited by histamine & other H2 agonists in a dose-dependent, competitive manner; the degree of inhibition parallels the concentration of the drug in plasma over a wide range. The H2 antagonists also inhibit acid secretion elicited by gastrin &, to a lesser extent, by muscarinic agonists. Importantly, these drugs inhibit basal (fasting) & nocturnal acid secretion & that stimulated by food, sham feeding, fundic distention, & various pharmacological agents; this property reflects the vital role of histamine in mediating the effects of diverse stimuli. The H2 antagonists reduce both the volume of gastric juice secreted & its H+ concentration. The output of pepsin, which is secreted by the chief cells of gastric glands (mainly under cholinergic control), generally falls in parallel with the reduction in volume of gastric juice. /H2 antagonists/ Cimetidine blocks H2-receptors, which in part are responsible for the inflammatory response, in the cutaneous blood vessels of humans. The effects of cimetidine, omeprazole and atropine sulfate on the healing of acetic acid-induced gastric ulcers in rats with limited food intake time (9:00-10:00 am and 5:00-6:00 pm) were evaluated 15 days after the acid injection. Oral repeated admin of cimetidine (25-100 mg/kg twice daily) or omeprazole (10-50 mg/kg once daily) dose dependently accelerated ulcer healing. ... A single oral admin of omeprazole (50 mg/kg) or cimetidine (100 mg/kg) resulted in potent and long-lasting anti-acid secretory and gastrin-releasing actions. The degree and duration of anti-acid secretion by atropine sulfate were equal to those of cimetidine, but the elevation of gastrin release by atropine sulfate was weak and temporary. These results indicate that the gastric ulcers of rats with a limited food intake time are useful for evaluating the healing effects of cimetidine and omeprazole on gastric ulcers. In addition, the effects of both drugs may be related to the incr gastrin release rather than to the reduced acid secretion. Both KB-5492, a new anti-ulcer agent, and cimetidine, admin po at 25-200 mg/kg, dose-dependently prevented cysteamine (400 mg/kg, sc)-induced duodenal ulcers in rats with ED50 values of 63 and 40 mg/kg, respectively. Anti-ulcer doses of cimetidine, but not KB-5492, inhibited gastric acid hypersecretion induced by cysteamine (400 mg/kg, sc). In contrast, anti-ulcer doses of KB-5492, but not cimetidine, incr duodenal HC03- secretion in normal anesthetized rats. These findings suggest that KB-5492 prevents cysteamine-induced duodenal ulcers by stimulating duodenal HC03- secretion, whereas cimetidine does so by inhibiting cysteamine-induced gastric acid hypersecretion.

Pharmacodynamics

Cimetidine is a histamine H₂-receptor antagonist. It reduces basal and nocturnal gastric acid secretion and a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli including food, caffeine, insulin, betazole, or pentagastrin. It is used to treat gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. Cimetidine inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Cimetidine include an increase in gastric bacterial flora such as nitrate-reducing organisms.