indication

For the treatment and the management of acid-reflux disorders (GERD), peptic ulcer disease, heartburn, and acid indigestion.

pharmacology

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.

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.

toxicity

Symptoms of overdose include nausea, vomiting, diarrhea, increased saliva production, difficulty breathing, and a fast heartbeat.

biotransformation

Hepatic

absorption

Rapid 60-70%

half life

2 hours

route of elimination

The principal route of excretion of cimetidine is the urine.

drug interactions

Acenocoumarol: Cimetidine may increase the anticoagulant effect of acenocoumarol.

Alfentanil: Increases the effect of the narcotic

Alprazolam: Cimetidine may increase the effect of the benzodiazepine, alprazolam.

Aminophylline: Cimetidine may increase the serum concentration of aminophylline by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of aminophylline if cimetidine is initiated, discontinued or dose changed.

Amitriptyline: Cimetidine may increase the effect of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if cimetidine is initiated, discontinued or dose changed.

Amoxapine: Cimetidine may increase the effect of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if cimetidine is initiated, discontinued or dose changed.

Anisindione: Cimetidine may increase the anticoagulant effect of anisindione.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Atazanavir: This gastric pH modifier decreases the levels/effects of atazanavir

Carbamazepine: Cimetidine may increase the serum concentration of carbamazepine during the first few days of concomitant therapy. Monitor for changes in the therapeutic and adverse effects of carbamazepine if cimetidine is initiated, discontinued or dose changed.

Carmustine: Increases myelosuppression caused by carmustine

Cefditoren: H2-Antagonists such as cimetidine may decrease the serum concentration of cefditoren. Cefditoren prescribing information recommends to avoid concomitant use with H2-antagonists (eg, famotidine, ranitidine) and antacids as well. Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided.

Chlordiazepoxide: Cimetidine may increase the effect of the benzodiazepine, chlordiazepoxide.

Clomipramine: Cimetidine may increase the effect of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if cimetidine is initiated, discontinued or dose changed.

Clonazepam: Cimetidine may increase the effect of the benzodiazepine, clonazepam.

Clorazepate: Cimetidine may increase the effect of the benzodiazepine, clorazepate.

Clozapine: Cimetidine may increase the serum concentratin of clozapine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if cimetidine is initiated, discontinued or dose changed.

Codeine: Cimetidine may decrease the therapeutic effect of codeine by decreasing its metabolism to its active metabolite, morphine. Monitor for changes in the therapeutic effect of codeine if cimetidine is initiated, discontinued or dose changed.

Desipramine: Cimetidine may increase the effect of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if cimetidine is initiated, discontinued or dose changed.

Diazepam: Cimetidine may increase the effect of the benzodiazepine, diazepam.

Dicumarol: Cimetidine may increase the anticoagulant effect of dicumarol.

Dihydroquinidine barbiturate: Increases the effect of quinidine

Dofetilide: Increases effect/toxicity of dofetilide

Donepezil: Possible antagonism of action

Doxepin: Cimetidine may increase the effect of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if cimetidine is initiated, discontinued or dose changed.

Dyphylline: Increases the effect of theophylline

Enoxacin: Cimetidine may decrease the absorption of enoxacin.

Epirubicin: Cimetidine can increase epirubicin levels

Estazolam: Cimetidine may increase the effect of the benzodiazepine, estazolam.

Ethotoin: Increases the effect of hydantoin

Fentanyl: Cimetidine, a moderate CYP3A4 inhibitor, may decrease the metabolism of fentanyl. Closely monitor changes in the therapeutic and adverse effects of fentanyl if cimetidine is initiated, discontinued or dose changed.

Flecainide: Cimetidine, a moderate CYP2D6 inhibitor, may decrease the metabolism of flecainide.

Flurazepam: Cimetidine may increase the effect of the benzodiazepine, flurazepam.

Fosphenytoin: Cimetidine may increase the serum concentration of fosphenytoin by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of fosphenytoin if cimetidine is initiated, discontinued or dose changed.

Galantamine: Possible antagonism of action

Halazepam: Cimetidine may increase the effect of the benzodiazepine, halazepam.

Heroin: Cimetidine increases the effect of the narcotic

Imipramine: Cimetidine may increase the effect of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if cimetidine is initiated, discontinued or dose changed.

Itraconazole: The H2-receptor antagonist, cimetidine, may decrease the absorption of itraconazole.

Ketazolam: Cimetidine may increase the effect of the benzodiazepine, ketazolam.

Ketoconazole: The H2-receptor antagonist, cimetidine, may decrease the absorption of ketoconazole.

Labetalol: Cimetidine may increase the serum concentration of labetolol by decreasing its metabolism.

Lidocaine: Increases the effect and toxicity of lidocaine

Mephenytoin: Increases the effect of hydantoin

Metformin: Cimetidine may increase the therapeutic and adverse effects of metformin by increasing its serum concentration. Consider alternate therapy.

Methadone: Cimetidine, a moderate CYP3A4 inhibitor, may increase the serum concentration of metahdone, a CYP3A4 substrate. Monitor for changes in the therapeutic and adverse effects of methadone if cimetidine is initiatied, discontinued or dose changed.

Metoprolol: Cimetidine may increase the serum concentration of metoprolol by decreasing its metabolism.

Midazolam: Cimetidine may increase the effect of the benzodiazepine, midazolam.

Moclobemide: Cimetidine may increase the serum concentration of moclobemide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of moclobemide if cimetidine is initiated, discontinued or dose changed.

Nalbuphine: Increases the effect of the narcotic

Nifedipine: Cimetidine may increase the effect of the calcium channel blocker, nifedipine.

Nimodipine: Cimetidine increases the effect of the calcium channel blocker, nimodipine.

Nitrendipine: Cimetidine increases the effect of the calcium channel blocker, nitrendipine.

Nortriptyline: Cimetidine may increase the effect of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if cimetidine is initiated, discontinued or dose changed.

Oxtriphylline: Cimetidine may increase the serum concentration of oxtriphylline by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of oxtriphylline if cimetidine is initiated, discontinued or dose changed.

Oxycodone: Cimetidine, a moderate CYP3A4 inhibitor, may decrease the metabolism of oxycodone. Monitor for changes in the therapeutic and adverse effects of oxycodone if cimetidine is initiated, discontinued or dose changed.

Oxymorphone: Increases the effect of the narcotic

Phenytoin: Cimetidine may increase the therapeutic effect of phenytoin.

Posaconazole: Significant decrease of posaconazole levels

Pramipexole: Cimetidine may increase the effect and toxicity of pramipexole.

Prazepam: Cimetidine may increase the effect of the benzodiazepine, prazepam.

Procainamide: The histamine H2-receptor antagonist, cimetidine, may increase the effect of procainamide.

Propoxyphene: Cimetidine, a moderate CYP3A4 inhibitor, may decrease the metabolism of propoxyphene. Monitor for changes in the therapeutic and adverse effects of propoxyphene if cimetidine is intitiated, discontinued or dose changed.

Propranolol: Cimetidine may increase the serum concentration of propranolol by decreasing its metabolism.

Protriptyline: Cimetidine may increase the effect of tricyclic antidepressant, protriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if cimetidine is initiated, discontinued or dose changed.

Quazepam: Cimetidine may increase the effect of the benzodiazepine, quazepam.

Quinidine: Cimetidine may increase the serum concentration of quinidine. Monitor for changes in the therapeutic and adverse effects of quinidine if cimetidine is initiated, discontinued or dose changed.

Quinidine barbiturate: Increases the effect of quinidine

Rivastigmine: Possible antagonism of action

Sildenafil: Increases the effect and toxicity of sildenafil

Sufentanil: Increases the effect of the narcotic

Tacrine: The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Cimetidine, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Cimetidine is initiated, discontinued or if the dose is changed.

Tacrolimus: Cimetidine may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Cimetidine therapy is initiated, discontinued or altered.

Tamoxifen: Cimetidine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.

Tamsulosin: Cimetidine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cimetidine is initiated, discontinued, or dose changed.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Theophylline: Cimetidine may increase the effect of theophylline.

Ticlopidine: Cimetidine may increase Ticlopidine levels. Avoid concomitant therapy.

Timolol: Cimetidine may increase the serum concentration of timolol by decreasing its metabolism.

Tizanidine: Cimetidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Tolazoline: Anticipated loss of efficacy of tolazoline

Tolterodine: Cimetidine may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.

Tramadol: Cimetidine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Cimetidine may decrease the effect of Tramadol by decreasing active metabolite production.

Trazodone: The CYP3A4 inhibitor, Cimetidine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Cimetidine is initiated, discontinued or dose changed.

Triazolam: Cimetidine may increase the serum concentration of triazolam by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of triazolam if cimetidine is initiated, discontinued or dose changed.

Trimipramine: Cimetidine may increase the effect of tricyclic antidepressant, trimipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if cimetidine is initiated, discontinued or dose changed.

Vilazodone: Cimetidine may decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Consider using an alternative H2-antagonist to avoid the risk of selective serotonin reuptake inhibitor (SSRI) toxicity. Monitor for increased therapeutic or toxic effects of SSRI if cimetidine is initiated/dose increased, or decreased effects if cimetidine is discontinued/dose decreased.

Warfarin: Cimetidine may increase the serum concentration of warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if cimetidine is initiated, discontinued or dose changed.

Zaleplon: Cimetidine may increase the serum concentration of zaleplon by decreasing its metabolism. Reduce the initial dose of zaleplon to 5 mg in patients receiving cimetidine.