Siamidine

Cimetidine.

SIAMIDINE (200 MG TABLET): 200 mg: Each tablet contains Cimetidine 200 mg.
SIAMIDINE (400 MG TABLET): Each tablet contains Cimetidine 400 mg.
SIAMIDINE INJECTION (100 MG/ML): Each ampoule (2 mL) contains cimetidine (as hydrochloride) 200 mg.
Clear, colorless sterile solution in clear glass ampoule.

Pharmacology: Pharmacodynamics: Cimetidine is a H₂ antagonist which is a competitive H₂ blocker that inhibit histamine at H₂ receptor of gastric parietal cells which inhibits gastric acid secretion. Cimetidine inhibits both daytime and nighttime basal gastric acid, and also when stimulated by food, insulin, histamine, pentagastrin, and caffeine.
Pharmacokinetics: Film-coated tablet: Cimetidine is rapidly and well absorbed following oral administration, the bioavailability is approximately 60%. Peak plasma concentration occurs after about 45-90 minutes and the blood concentration remain above those required to provide 80% inhibition of basal gastric acid secretion for 4-5 hours following a 300 mg dose. Cimetidine is widely distributed and has a volume of distribution of about 1 L/Kg and is weakly bound to plasma protein about 20%. Cimetidine crosses the placenta and is distributed into breast milk. Cimetidine is metabolized in the liver to the major metabolite sulfoxide and also 5-hydroxymetyl derivatives. 48% of an oral dose is excreted unchanged in urine. The elimination half-life from plasma is about 2 hours.
Injection: The blood concentration of Cimetidine remains above those required to provide 80% inhibition of basal gastric acid secretion for 4-5 hours following a parenteral dose of 300 mg. Cimetidine is widely distributed and has a volume of distribution of about 1 L/Kg and is weakly bound to plasma protein about 20%. Cimetidine crosses the placenta and is distributed into breast milk. Cimetidine is metabolized in the liver to the major metabolite sulfoxide and 5-hydroxylmetyl derivatives. 75% of an intravenous dose is excreted unchanged in urine. The elimination half-life from plasma is about 2 hours.

Duodenal and benign gastric ulceration, gastroesophageal reflux disease, other conditions where reduction of gastric acid secretion is likely to be beneficial and pathologic GI hypersecretory conditions (e.g. Zollinger-Ellison Syndrome).

Recommended dose: Film-coated tablet: 1. Duodenal ulcer or benign gastric ulceration: A single daily dose of 800 mg at bed time or 400 mg twice daily with breakfast and at bedtime. Treatment should be given initially for at least four weeks for duodenal ulcer (six weeks in benign gastric ulcer, eight weeks in ulcer associated with continued non-steroidal anti-inflammatory agents) even if symptomatic relief has been achieved sooner.
Maintenance dose: 400 mg at bedtime, or 400 mg in the morning and at bedtime.
2. Gastroesophageal reflux disease: 400 mg four times a day, with meals and at bedtime, for 4-12 weeks.
3. For relieving symptoms due to excessive gastric acid (acid indigestion, heartburn, or sour stomach): 200 mg daily (maximum dose is 400 mg/day).
4. Pathologic GI hypersecretory conditions (e.g. Zollinger-Ellison Syndrome): 400 mg four times a day.
Pediatric: Safety and efficacy are limited. Cimetidine is not recommended for children younger than 16 years, unless anticipated benefits outweigh potential risks. In very limited experience, Cimetidine 20-40 mg/kg/day in divided dose has been used. Nonprescription use is not recommended in children younger than 12 years.
Injection: Adult: 300 mg every 6 to 8 hours given by intravenous or intramuscular injection, or 37.5 mg/hr continuous IV infusion (with or without a 150 mg intravenous loading dose). The total daily dose should not exceed 2.4 g.
Pediatric: Cimetidine is not recommended for children younger than 16 years, unless anticipated benefits outweigh potential risks. In very limited experience, Cimetidine 20-40 mg/kg/day in divided dose has been used.
Renal impairment: In severe renal impairment, the recommended dose is 300 mg every 12 hours, may increase frequency with caution. When hepatic impairment is also present, further reductions in dosage may be necessary. Alternative recommendations: See table.

Click on icon to see table/diagram/image

Haemodialysis: Cimetidine is removed by haemodialysis, therefore it should be administered at the end of dialysis and every 12 hours during the interdialysis period.
Dose after dialysis: CRRT (continuous renal replacement therapy): Administer 50% of normal dose.
Peritoneal dialysis: 300 mg every 8 to 12 hours.
Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage adjustment may be needed in patient with both renal and hepatic impairment.
Mode of Administration: Film-coated tablet: Cimetidine can be given orally, the total daily dose should not normally exceed 2.4 g. Antacid may be given as necessary for relief of pain in patients with ulcers but should not be administered simultaneously with oral Cimetidine, since antacids may interfere with absorption.
Injection: Cimetidine may be given parenterally by the intravenous or intramuscular routes in patients unable to take oral medications or in patients hospitalized with pathological hypersecretory conditions or intractable ulcers. Cimetidine is physically compatible with most intravenous solution such as sodium chloride 0.9%, 5% or 10% dextrose and lactated Ringer's solution.
IM injection: Cimetidine may be given undiluted or diluted 300 mg to 20 mL and injected over at least 5 minutes.
IV injection: 300 mg of Cimetidine is diluted to final volume of 20 mL with 0.9% sodium chloride injection or another compatible IV solution and injected over at least 5 minutes.
Intermittent IV infusion: 300 mg of Cimetidine is diluted to at least 50 mL of 5% dextrose injection or another compatible IV solution and infused over 15-20 minutes.
Continuous IV infusion: 900 mg of Cimetidine is diluted to 100 to 1000 mL of a compatible IV solution and infused over 24 hours. Volumetric pump recommended for 24-hour volumes less than 250 mL. The drug usually is infused at a rate of 37.5 mg/hour, but the rate should be individualized according to patient requirements. An initial 150 mg IV loading dose may be required.

Overdose and treatment: Cimetidine has a large therapeutic window, and no more than minimal toxicity is expected even large overdoses. The total daily dose should not normally exceed 2.4 g. Doses up to 20 g were associated with transient adverse effects similar to those occurring with usual doses. For the treatment of Cimetidine overdosage, the usual measures to remove unabsorbed drug from gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.
Injection: There is no specific antidote for Cimetidine, management of mild to moderate toxicity is symptomatic and supportive treatment. For severe toxicity, intravenous fluids for hypotension, supportive care for CNS depression may be needed.

Cimetidine is contraindicated in patients with a history of hypersensitivity to Cimetidine, or any component of the product.

According to Beers Criteria, Cimetidine should be avoided in older adults with or at high risk of delirium because of potential of inducing or worsening delirium.
Reversible confusional states have been reported and increased risk in severely ill patients, advancing age (i.e. 50 years of age or older), and preexisting liver or renal disease; discontinuation may be warranted.
Cimetidine may increase risk of strongyloidiasis hyperinfection in immunocompromised patient.
Symptomatic response to Cimetidine therapy does not rule out the presence of gastric malignancy.
Injection: Cardiac arrhythmias and hypotension, with rapid administration by IV bolus injection, have been reported rarely.
Use in Children: Cimetidine is not recommended to use in pediatric patient under 16 years of age, unless benefit outweighs risk.

Pregnancy: Pregnancy category: B.
Cimetidine can cross the placenta. An increased risk of congenital malformations or adverse event in the newborn has generally not been observed following maternal use of these agents during pregnancy. H₂ antagonists may be used for aspiration prophylaxis prior to cesarean delivery. However, the use of Cimetidine during pregnancy should be avoided unless considered essential by the physician.
Lactation: Cimetidine is excreted in breast milk. The concentration of Cimetidine in maternal serum in comparison to breast milk is highly variable. Breast-feeding is not recommended unless considered essential by the physician.

Adverse reaction to Cimetidine is generally infrequent. The common side effects may include diarrhea, gastrointestinal disturbance, headache, dizziness, tiredness, somnolence, gynecomastia, rash, myalgia and arthralgia.
Other adverse reactions may include: Central nervous system: Headache, reversible confusional states.
Cardiovascular: Rare case of bradycardia, tachycardia, atrioventricular heart block; (injection): cardiac arrhythmias and hypotension following rapid IV administration.
Dermatologic: Very rare case of Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme, exfoliative dermatitis, generalized exfoliative erythroderma.
Endocrine: Gynecomastia.
Gastrointestinal: Diarrhea.
Hematologic: Agranulocytosis, neutropenia.
Hepatic: Increased in serum AST, increased in serum ALT.
Renal: Increased in plasma creatinine.
Musculoskeletal: Arthralgia, myalgia.
Miscellaneous: Extremely rare case of strongyloidiasis hyperinfection in immunocompromised patients.

Drug metabolized by hepatic microsomal enzymes (Cytochrome P450): Cimetidine inhibits cytochrome P450 (CYP) , including CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP2E1, CYP3A4, CYP3A3 and CYP2C18. Inhibition of these enzymes may result in increased plasma levels of certain drugs including coumarin anticoagulants (e.g., warfarin), phenytoin, propanolol, some benzodiazepines, lidocaine, metronidazole, triamterene, some tricyclic antidepressants, and theophylline.
Antiarrhythmic agent: Concurrent use of Cimetidine and antiarrhythemic agent such as disopyramide, dofetilide, procainamide, quinidine, sotalol may result in prolong QT interval and increase the risk of life-threatening cardiac arrhythmias, including torsades de pointes cardiac arrest.
Antifungal: Cimetidine alters gastric pH and may decrease the absorption of some azole antifungals such as ketoconazole. If concomitant therapy with such drugs is needed, they should be administered at least 2 hours prior to Cimetidine administration.
Anticoagulant: Concurrent use of Cimetidine and warfarin may result in an increased risk of bleeding. If the drugs must be administered concurrently, prothrombin time should be carefully monitored and dosage adjustment of the anticoagulant may be necessary.
Myelosuppressive drugs: Cimetidine may potentiate the myelosuppressive effects (e.g. neutropenia, agranulocytosis) of myelosuppressive drugs such as alkylating agents (e.g. carmustine), antimetabolites or therapies (e.g, radiation).
Film-coated tablet: Antacid: Antacids may reduce the absorption of Cimetidine. To prevent any potential interaction, antacids should probably be taken 1 hour before or after Cimetidine in the fasting state, or 1 hour after Cimetidine is taken with food.

Store below 30°C.

Antacids, Antireflux Agents & Antiulcerants

A02BA01 - cimetidine ; Belongs to the class of H2-receptor antagonists. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).

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