A 45-year-old woman with a history of opioid use disorder and HIV infection is brought to the emergency department due to worsening lethargy. The patient receives methadone maintenance therapy, which she recently restarted after being hospitalized for an HIV-related infection. Her infection improved after inpatient treatment, and she continues to take appropriate antimicrobials as an outpatient. Her current temperature is 37 C (98.6 F), blood pressure is 116/68 mm Hg, pulse is 90/min, and respirations are 10/min. On physical examination, the patient is somnolent and withdraws all extremities to painful stimuli. The pupils are small and sluggish to react. Brain imaging reveals no new findings, and renal function tests are within normal limits. Use of which of the following medications most likely contributed to this patient's current condition?

Question

A 45-year-old woman with a history of opioid use disorder and HIV infection is brought to the emergency department due to worsening lethargy.  The patient receives methadone maintenance therapy, which she recently restarted after being hospitalized for an HIV-related infection.  Her infection improved after inpatient treatment, and she continues to take appropriate antimicrobials as an outpatient.  Her current temperature is 37 C (98.6 F), blood pressure is 116/68 mm Hg, pulse is 90/min, and respirations are 10/min.  On physical examination, the patient is somnolent and withdraws all extremities to painful stimuli.  The pupils are small and sluggish to react.  Brain imaging reveals no new findings, and renal function tests are within normal limits.  Use of which of the following medications most likely contributed to this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3c56_b7f3_9249_e55e54bdb693_MD0001_00 Methadone is a mu-opioid receptor agonist used for maintenance treatment of opioid use disorder. It has a long half-life, which allows it to effectively suppress cravings and withdrawal symptoms. Like all opioid medications, methadone carries a risk of overdose, which is characterized by somnolence, miosis, and respiratory depression (ie, bradypnea). Another side effect is QTc prolongation, which can predispose to torsade de pointes. Methadone is extensively metabolized by the cytochrome P-450 system, particularly by CYP3A4. In this case, the patient likely received fluconazole, an antifungal medication that is used in the treatment of cryptococcal meningitis (which typically occurs in patients with a CD4 count <100 cells/µL). Fluconazole inhibits CYP3A4, which can increase plasma methadone concentration and lead to opioid toxicity. Interestingly, not all P-450 3A4 inhibitors prolong methadone effects; other medications known to cause similar interactions with methadone include voriconazole, ketoconazole, ciprofloxacin, clarithromycin, cimetidine, and fluvoxamine. (Choices A and B) Atovaquone and dapsone are alternative agents used to prevent pneumocystis pneumonia in patients with trimethoprim-sulfamethoxazole allergy. Common side effects of dapsone include hemolytic anemia and methemoglobinemia, particularly in patients with glucose-6-phosphate dehydrogenase deficiency. Neither medication has significant interactions with methadone. (Choice D) Rifampin is used (in combination with other antibiotics) in the treatment of multiple mycobacterial infections (eg, tuberculosis, mycobacterium avium complex). It is a cytochrome P-450 inducer and can result in lower plasma concentrations of methadone, thereby decreasing its effects. (Choice E) Valganciclovir is used for treatment and secondary prophylaxis of cytomegalovirus retinitis. Side effects include bone marrow suppression and diarrhea. It does not interact with methadone. Educational objective: Methadone is a mu-opioid receptor agonist used for maintenance treatment for opioid use disorder; it is metabolized by the cytochrome P-450 system, particularly by CYP3A4. Certain inhibitors of CYP3A4 (eg, azoles, fluvoxamine, ciprofloxacin, clarithromycin, cimetidine) can increase plasma methadone concentration and lead to opioid toxicity (eg, sedation, respiratory depression, miosis).

A 45-Year-Old Woman with a History of Opioid Use Disorder