Citalopram Cimetidine

Citalopram (Celexa) [Antidepressant/SSRI] WARNING Closely monitor for worsening depression or emergence of suicidality, particularly in pts <24 y Uses Depression Action SSRI Dose Initial 20 mg/d, may t to 40 mg/d X in elderly hqjatic/renal insuff Caution [C, +/-] Hx of mania, Szs pts at risk for suicide Contra MAOI or w/in 14 d of MAOI use Disp Tabs, cap, soln SE Somnolence, insomnia, anxiety, xerostomia, diaphoresis, sexual dysfxn Notes May cause X Na /SIADH Interactions t Effects W/ azole antifungals, cimetidine, Li, macrolides, EtOH t effects OF BBs, carbamazepine, CNS drugs, warfarin X effects W/ carbamaz ine X effects OF phenytoin may cause fatal Rxn W/ MAOIs EMS Use caution w/ CNS depressants, may need a reduced dose concurrent EtOH... 

Coadministration of cimetidine reduced citalopram oral clearance by 29%, whereas the addition of fluvoxamine caused a significant increase in plasma concentrations of citalopram. At this time, esci-talopram is considered unbkely to be involved in cbnically important pharmacokinetic interactions, althongh coadministration of escitalo-pram and desipramine resnlted in a donbling of the area nnder the cnrve for desipramine. ... 

Citalopram Cimetidine Reduced oral clearance of citalopram... 

A two-period crossover, double-blind study in 20 subjects given fluoxetine 20 mg or a placebo daily for 28 days, with zolmitriptan 10 mg on day 28, found that the pharmacokinetics of zolmitriptan were unaffected by fluoxetine. Only very slight changes were seen in the pharmacokinetics of its active metabolite. Sertraline, paroxetine, and citalopram are also not expected to alter the pharmacokinetics of zolmitriptan. However, fluvoxamine, a CYP1A2 inhibitor, is predicted to increase levels of zolmitriptan, based on the known interaction with cimetidine (see Triptans Zolmitriptan + Cimetidine , p.608). 

Citalopram, escitalopram, paroxetine and sertraline levels are moderately increased by cimetidine but the only clinically relevant effect appears to be a slight increase in adverse effects with sertraline. 

PriskornM, Larsen F, Segonzac A, Moulin M. Pharmacokinetic interaction study of citalopram and cimetidine in healthy subjects. EurJ Clin Pharmacol (1997) 52, 241-2. 

Twelve healthy subjeets were given eitalopram 40 mg daily for 21 days and then for the next 8 days they were also given cimetidine 400 mg twice daily. The cimetidine caused a 29% decrease in the oral clearance of the citalopram, a 39% rise in its maximum serum levels and a 43% increase in its AUC. Some changes in the renal clearance of the citalopram metabolites were also seen. ... 

Cimetidine 400 mg twice daily increased the mean plasma level of escitalopram by about 70%. There was also a 22% increase in the maximum plasma level of citalopram, but this was not considered to be clinically significant. ... 

The authors of the citalopram study say that while cimetidine certainly causes an increase in the serum levels of citalopram, the extent is only moderate and because the drug is well tolerated and there are very considerable pharmacokinetic variations between individual subjects, they consider that there is no need to reduce the citalopram dosage. This advice is most likely applicahle to escitalopram, the S-isomer of citalopram. However, the manufacturer of escitalopram suggests caution, and advises that a reduction in the dose of escitalopram may he necessary (based on monitoring of adverse effects) during concurrent treatment. ... 

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