Pimozide SSRIs

Hypersensitivity to SSRIs in combination with a monoamine oxidase inhibitor (MAOl), or within 14 days of discontinuing an MAOl administration of thioridazine with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued coadministration of fluvoxamine with cisapride, thioridazine or pimozide concomitant use of thioridazine with paroxetine concomitant use of pimozide with sertraline coadministration of sertraline oral concentrate and disulfiram. 

Drugs that may be affected by SSRIs Drugs that may be affected by SSRIs include alcohol, benzodiazepines, beta blockers, buspirone, carbamazepine, cisapride, clozapine, cyclosporine, diltiazem, digoxin, haloperidol, hydantoins, lithium, methadone, mexiletine, nonsedating antihistamines, NSAIDs, olanzapine, phenothiazines, phenytoin, pimozide, procyclidine, ritonavir, ropivacaine, sumatriptan, sulfonylureas, sympathomimetics, tacrine, theophylline, tolbutamide, tricyclic antidepressants, and warfarin. 

There are several antipsychotics that are substrates to CYP2D6 (von Bahr et ah, 1991 Jerling et ah, 1996 Ring et ah, 1996 (Fang and Gorrod, 1999 Flockhart and Oesterheld, 2000) (Table 26.3). Moreover, several antipsychotics may act as inhibitors of CYP2D6-mediated biotransformation. These include thioridazine, chlorpromazine, haloperidol, fluphenazine, and pimozide (Desta et ah, 1998 Shin et ah, 1999). Of particular salience is the fact that the serotonin selective reuptake inhibitors (SSRIs) fluoxetine and paroxetine are metabolized to a significant extent by this isoenzyme. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Clinically important, potentially hazardous interactions with amiodarone, azithromycin, bepredil, bosentan, bretylium, cisapride, clarithromycin, disopyramide, erythromycin, erythromycin fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, metronidazole, miconazole, nefazodone, nilotinib, paroxetine, pimozide, probucol, procainamide, quinidine, quinine, ritonavir, saquinavir, sertraline, sotalol, SSRIs, terfenadine, troleandomycin, voriconazole, zileuton, ziprasidone... 

Pimozide levels are expected to rise when used with fluoxetine, fluvoxamine, paroxetine, or sertraline, which would increase the risk of potentially fatal torsade de pointes arrhythmias. The use of SSRIs and pimozide has also led to extrapyramidal adverse effects, oculogyric crises and sedation in rare cases. 

The SSRIs can, to varying degrees inhibit the cytochrome P450 isoenzyme CYP2D6 (and fluvoxamine possibly also inhibits CYP3A4) by which pimozide is metabolised. Concurrent use would therefore be expected to lead to raised pimozide levels. 

Evidence is limited, however the interaction is potentially severe as raised pimozide levels can cause torsade de pointes arrhythmias, which can be fatal. The manufacturers of pimozide contraindicate its use with SSRIs, and in the UK they specifically name sertraline, paroxetine, and citalo-pram which has been seen to cause QT prolongation with pimozide, and its isomer, escitalopram. The US manufacturers additionally contraindicate fluvoxamine." Neither manufacturer mentions fluoxetine (except with regard to the possibility of additive bradycardia"), but as it is known to have greater effects on CYP2D6 than either sertraline or citalopram, it would seem prudent to also consider it as contraindicated. 

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