Tips on Averting Cimetidine Drug Interactions

After cimetidine was releasedin the late 1970s,case reports of clinicallysignificant drug interactionsquickly emerged. ^1-3Controlled trials soon validated theseinitial clinical observations. Since1983, when a comprehensive reviewof cimetidine drug interactions waspublished,⁴ more interactions havebeen reported, as use of this agenthas increased because of cost constraintsand the rapid growth of managedcare. Examples of well-documentedinteractions are listed in theTable.MECHANISMS OF CIMETIDINEDRUG INTERACTIONS
Cimetidine inhibits the cytochromeP-450 system and thus reduceshepatic drug metabolism. Becauseit inhibits several P-450 isoenzymes,it decreases the clearance ofnumerous drugs. ⁵ Cimetidine wasinitially reported to decrease hepaticblood flow, but this finding has beenquestioned as a mechanism of druginteraction.^6,7 Some cimetidine interactionsresult from inhibition of therenal cation transport system.⁸CIRCUMVENTINGINTERACTIONS
The most prudent approach is tocircumvent drug interactions. Whenhistamine type 2-receptor antagonist(H₂ blocker) therapy is indicated, useranitidine, famotidine, or nizatidine toavoid the interactions associated with cimetidine. A proton pump inhibitoris another alternative.REMEMBER TO CHECKFOR INTERACTIONS
In the extremely busy environmentof patient care, it is easy to forgetabout cimetidine drug interactions.For example, when a patient ishospitalized, cimetidine is likely to becontinued and potentially interactingdrugs (eg, phenytoin or theophylline)may be added. In the outpatient setting,cimetidine may be prescribedbecause it is on the formulary of amanaged care organization, and itmay interact with a drug that the patientis already receiving.It may be helpful simply to recognizecimetidine as a drug with numerousinteractions rather than attemptto remember all the specific interactions.Quickly screen for potential interactions(eg, with the Table in thisarticle or with handheld software).Alternatively, ask a clinical pharmacycolleague to check for any clinicallysignificant interactions.CIMETIDINE DOSERELATIONSHIP ANDDRUG INTERACTIONS
If nonprescription-strength cimetidineis taken at the recommendeddosages, clinically relevant druginteractions are unlikely to occur.⁹However, many patients take prescription-strength dosages of overthe-counter (OTC) medications.Therefore, it is wise to ask patients about the use and dosages of OTCdrugs (and herbal medicines) as wellas prescription medications.Most cimetidine drug interactionswere discovered when the standarddosage was 300 mg 4 timesdaily (1200 mg/d). Although for thepast several years the common prescriptiondosage has been 400 mgtwice daily--which may not produceas many interactions as higherdosages--it is prudent to circumventpotential interactions until sufficientstudies are conducted with currentlyused dosages.Finally, bear in mind that cimetidineis renally eliminated. In patientswith decreased renal function, relatively low dosages are, in fact, equivalentto "normal" or high dosages.Therefore, drug interactions mayoccur in this setting because serumconcentrations of cimetidine are highenough to inhibit the metabolism ofother agents.WHEN TO BE MOST ALERTFOR INTERACTIONS
The times of greatest risk forcimetidine drug interactions are:

• At higher dosages (eg, 1200 mg/d).
• At current typical dosages (eg,800 mg/d) in patients with renaldysfunction.
• When cimetidine is added ordiscontinued.

References:

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