Int J Emerg Med (2010) 3:81–84 medications have the ability to induce or inhibit one or many of the CYP450 enzymes. This induction or inhibition can cause unforeseen variances in drug metabolism, adverse events, and therapeutic failures. Concomitant administration of inducers or inhibitors with other drugs that are metabolized by the CYP450 system can result in altered metabolism and kinetics throughout the body. Many well-known drugs alter P450 enzyme levels. Most CYP450 drug interactions can be managed through vigilance and dose adjustment. In examining the PIs affinity for CYP450 enzymes, lopinavir is a substrate of the enzyme CYP3A4, while ritonavir is a substrate of CYP1A2, 2B6, 2D6, and 3A4. Ritonavir also is a strong inhibitor of CYP2C8, 2D6, and 3A4. Due to the fact that perphenazine is a major substrate of CYP2D6, levels can be increased by 2D6 inhibitors, such as ritonavir. Quetiapine binds to CYP3A4 and 2D6 as a substrate; the PIs inhibit and also bind to 3A4 and 2D6 creating a larger amount of active quetiapine in the serum. The combination of these drugs increases the free amount of both perphenazine and quetiapine in the blood, predis- posing the patient to possible toxicity and unwanted side effects, such as priapism (see Table 1) [12]. Harrison et al. encountered a case of priapism in an HIV patient due to quetiapine and reported the possibility of a Table 1 CYP450 enzyme characteristics by medication [12] 83 drug interaction due to illicit amphetamine use [7]. Their case made no mention of any antiretroviral medication or PI their patient used, so a correlation between PI use and quetiapine could not be made. The current patient did not have any amphetamines in his system, as verified by a post- procedure urine toxicology screen. A review conducted by Sood et al. states that priapism, although rare, can occur with all atypical-antipsychotic medications [4]. As stated above, priapism can occur with initial doses, after years of use, or with the addition of new medications to a regimen. In reviewing 50 publications and cases regarding priapism and drug-drug reactions, there is no mention of priapism due to the combination of HAART medications and antipsychotics. Although the possibility exists that the patient would have developed priapism using one or both of the antipsychotics as a single agent, the immediate onset of this situation was enhanced and is most likely fully to blame upon previously altered CYP450 enzyme levels due to the HAART, specifically the patient’s PI. The Naranjo algorithm is a questionnaire designed to determine the likelihood of whether an adverse drug reaction is actually due to the drug rather than the result of other factors. It is the most widely used algorithm to assess such events and has been tested for internal validity