Antipsychotic-induced priapism in an HIV patient: a cytochrome P450-mediated drug interaction

Abstract

BackgroundWith upwards of 48% of human immunodeficiency virus (HIV)-infected persons having a probable psychiatric disorder, the possibility of cross-class drug interactions causing adverse effects or fatalities exists.AimsThis report discusses an emergent case of low-flow priapism caused by an interaction between a previously prescribed combination protease inhibitor (PI) and newly added antipsychotic medications.MethodsA 50-year-old HIV-positive man on highly active antiretroviral therapy (HAART), including the combination PI, lopinavir/ritonavir (Kaletra®), experienced an episode of priapism hours after beginning two new antipsychotic medications. Quetiapine (Seroquel®) and perphenazine (Trilafon®) were added to treat a diagnosed schizoaffective disorder.ResultsThe patient presented to the emergency department complaining of a constant, painful erection lasting approximately 42 h. Treatment with intracavernous ephedrine, irrigation, and aspiration helped achieve detumescence.ConclusionThis case displays the immediate and detrimental effects due to the addition of antipsychotic medications to previously altered cytochrome P450 (CYP450) enzyme levels. The inhibition of CYP450 enzymes 3A4 and 2D6 by the combination PI, lopinavir/ritonavir, was likely the major culprit in causing greater than expected free levels of perphenazine and quetiapine resulting in priapism.

Priapismo secundario a antipsicóticos: a propósito de un caso asociado a risperidona

“…1,2 , que podrían desaconsejar el uso de antipsicóticos con alta afinidad α-antagonista como la risperidona 6 o, en caso de su prescripción, imponer obligadamente una monitorización cercana. También se deben considerar posibles interacciones farmacocinéticas que eleven los niveles plasmáticos de los fármacos asociados con priapismo 13 . Adicionalmente se ha descrito que numerosos pacientes desarrollan erecciones prolongadas y no dolorosas antes del episodio pleno de priapismo: sin embargo, los pacientes no mencionan espontáneamente este problema (y tampoco lo abordan usualmente los facultativos) 11 .…”

Quetiapine-induced Priapism Requiring Frequent Emergency Admissions: A Case Report

“…The cytochrome P450 study was done to rule out any enzymatic or genetic abnormality interfering with metabolism of the above medications. 1 , 2 Urology was consulted and aspirated 15 cc of dark, red blood from the bilateral corpora after local anesthesia with 1% lidocaine. The patient was given 1000 mcg of phenylephrine and 750 mg of levofloxacin orally.…”

“… 3 , 4 , 5 In contrast to other cases, cytochrome P450 3A4 genetic testing was performed as our patient clearly has a propensity for priapism with use of daily dosed anti-psychotics including his prior history one year ago. 1 , 2 Furthermore, the patient denied taking more than the recommended daily dose of quetiapine and the absence of other side effects that have been previously linked to quetiapine overdose including somnolence, tachycardia, respiratory depression, and hypotension. 3 Any use of illicit substances or other medications were ruled out by GCMS.…”

“…As quetiapine and clonazepam are significant cytochrome P450 3A4 substrates, cytochrome genetic testing allowed a closer examination of the patient's enzymatic functioning. 1 We hypothesized there were likely malfunctioning hepatic cytochrome enzymes with a major role in the medications' metabolism either inherited or acquired ( Table 1 ). Upon review of his cytochrome lab results, the patient had CYP 3A4 CC genotype, which predicts normal enzyme activity.…”

Important Drug-Drug Interactions in HIV-Infected Persons on Antiretroviral Therapy: An Update on New Interactions Between HIV and Non-HIV Drugs

“…Geraci et al, reported a case of priapism starting 5-6 h after co-ingestion of perphenazine 8 mg daily (CYP2D6 substrate) and quetiapine 900 mg daily with lopinavir/ritonavir 400/100 mg twice daily, and lasting 42 h. Rapid elevations in the neuroleptic concentrations were postulated as the mechanism. The symptoms were managed with intracavernous ephedrine, irrigation and aspiration [50]. Although a formal pharmacokinetic trial is lacking, these cases illustrate that caution is warranted when quetiapine is coadministered with ritonavir-boosted regimens.…”