Due to her deteriorating lethargic state, a 45-year-old woman with a history of opiate use disorder and HIV infection is taken to the emergency room. The patient has recently resumed her methadone maintenance medication after being admitted to the hospital for an HIV-related illness. After receiving inpatient treatment, her illness became better, and she's still taking the right antibiotics as an outpatient. Her body temperature is at 37 C (98.6 F), blood pressure is 116/68 mm Hg, her pulse is 90 beats per minute, and her respirations are 10 beats per minute. During a physical examination, the patient is drowsy and withdraws all of his or her extremities in response to discomfort. The pupils are tiny and slow to respond. Renal function tests come back normal, and brain MRI shows no new abnormalities. Use of which of the following medications most likely contributed to this patient's current condition?

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Eductional Objective: In order to maintain therapy for opioid use disorder, methadone, a mu-opioid receptor agonist, is metabolized by the cytochrome P-450 system, in particular by CYP3A4. A number of CYP3A4 inhibitors, such as azoles, fluvoxamine, ciprofloxacin, clarithromycin, and cimetidine, can raise the plasma concentration of methadone and cause opioid toxicity (eg, sedation, respiratory depression, miosis).

Due to Her Deteriorating Lethargic State, a 45-Year-Old Woman with a History