In this case scenario, we outline the Paxlovid alprazolam interaction. A 42-year-old woman with a long-standing history of severe generalized anxiety disorder, managed with alprazolam 1 mg orally twice daily for several years, presented to the emergency department with marked sedation, confusion, slurred speech, and difficulty walking. Her husband reported that she had been unusually drowsy over the past day and nearly fell while moving around the house. She also complained of dizziness and generalized weakness.
Three days prior, she was diagnosed with COVID-19 and was prescribed Paxlovid (nirmatrelvir/ritonavir) for a five-day course. She continued her usual alprazolam regimen during this period. On examination, she was drowsy but arousable, with mild ataxia and dysarthric speech. Vital signs were stable, and basic laboratory tests, including renal function and electrolytes, were within normal limits.
The clinical picture was consistent with alprazolam toxicity caused by a drug-drug interaction with ritonavir, a component of Paxlovid. Ritonavir is a potent inhibitor of CYP3A4 (excellent board exam nugget), the primary enzyme responsible for metabolizing alprazolam in the liver. When CYP3A4 is inhibited, the metabolism of alprazolam slows dramatically, leading to a rapid increase in plasma concentrations. This can result in excessive sedation, respiratory depression, impaired coordination, and cognitive impairment, as seen in this patient.
Management of the Paxlovid alprazolam interaction involved holding alprazolam, providing supportive care, monitoring neurological status, and ensuring fall precautions. The patient and her caregivers were educated about the significant interaction between CYP3A4 inhibitors and benzodiazepines. This case highlights the importance of reviewing all medications, including chronic anxiolytics, before prescribing strong CYP3A4 inhibitors like ritonavir. Clinicians should reduce the dose of alprazolam to prevent potentially serious toxicity when Paxlovid is prescribed. If you are looking for more on alprazolam, it was part of my podcast series on the Top 200 drugs.
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