Cimetidine

Cimetidine can prolong the elimination of drugs metabolised by oxidation in the liver. Although pharmacological interactions with a number of drugs, e.g. Diazepam, Propranolol, have been demonstrated, only those with oral anticoagulants, phenytoin, theophylline and intravenous lidocaine appear, to date, to be of clinical significance. Close monitoring of patients on Cimetidine receiving oral anticoagulants or phenytoin is recommended and a reduction in the dosage of these drugs may be necessary.

Due to possible interaction with coumarins, close monitoring of prothrombin time is recommended when cimetidine is concurrently used.

Co-administration of therapeutic agents with a narrow therapeutic index, such as phenytoin or theophylline, may require dosage adjustment when starting or stopping concomitantly administered cimetidine.

Inhibition of certain cytochrome P450 enzymes (including CYP1A2, CYP2C9, CYP2D6 and CYP3A3/A4, and CYP2C18); Inhibition of these enzymes may result in increased plasma levels of certain drugs including warfarin-type coumarin anticoagulants (e.g. warfarin), tricyclic antidepressants (e.g. amitriptyline), class I antiarrhythmics (e.g. lidocaine), calcium channel blockers (e.g. nifedipine, diltiazem), oral sulfonylureas (e.g. glipizide), phenytoin, theophylline and metoprolol.

Dosage should be reduced in patients with impaired renal function according to creatinine clearance.

The following doses are suggested:

Creatinine clearance of 0 to 15ml per minute, 200mg twice a day;
Creatinine clearance of 15 to 30ml per minute, 200mg three times a day;
Creatinine clearance of 30 to 50ml per minute, 200mg four times a day;
Creatinine clearance of over 50 ml per minute, normal dosage.

Cimetidine is removed by haemodialysis, but not to any significant extent by peritoneal dialysis.

Alteration of gastric pH

The bioavailability of certain drugs may be affected. This can result in either an increase in absorption (e.g. atazanavir) or a decrease in absorption (e.g. some azole antifungals such as ketoconazole, itraconazole or posaconazole).

Cimetidine may potentiate the myelosuppressive effects (e.g. neutropenia, agranulocytosis) of chemotherapeutic agents such as carmustine, fluorouracil, epirubicin, or therapies such as radiation. Isolated cases of clinically relevant interactions have been documented with narcotic analgesics (e.g. morphine).

Competition for renal tubular secretion. This may result in increased plasma levels of certain drugs including procainamide, metformin, ciclosporin and tacrolimus.

Although tests in animals and clinical evidence have not revealed any hazards from the administration of cimetidine during pregnancy, both animal and human studies have shown that it does cross the placental barrier. As with most drugs, the use of cimetidine should be avoided during pregnancy unless essential.

Although tests in animals and clinical evidence have not revealed any hazards from the administration of cimetidine during lactation, both animal and human studies have shown that is excreted in breast milk. As with most drugs, the use of cimetidine should be avoided during lactation unless essential.

None known.