Nirmatrelvir and ritonavir and Trazodone interaction
Nirmatrelvir and ritonavir and Trazodone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Nirmatrelvir and ritonavir (Paxlovid) label · effective 2026-02-19
…(selective blocker of Na v 1.8 sodium channels): suzetrigine • Opioid antagonists: naloxegol • PDE5 inhibitor: sildenafil (Revatio ® ) when used for pulmonary arterial hypertension (PAH) • Sedative/hypnotics: triazolam, oral midazolam • Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin • Vasopressin receptor antagonists: tolvaptan ➢ Drugs that…
Sedative/hypnotics triazolam, oral midazolam ↑ triazolam ↑ midazolam Co-administration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4) ] .
Serotonin receptor 1A agonist/ serotonin receptor 2A antagonist flibanserin ↑ flibanserin Co-administration contraindicated due to potential for hypotension, syncope, and CNS depression [see Contraindications (4) ] .
A lower dose of trazodone should be considered.
Antidepressants bupropion ↓ bupropion and active metabolite hydroxy-bupropion Monitor for an adequate clinical response to bupropion. trazodone ↑ trazodone Adverse reactions of nausea, dizziness, hypotension, and syncope have been observed following co-administration of trazodone and ritonavir.
From the Trazodone (RALDESY TM) label · effective 2026-09-01
The use of RALDESY Should be avoided in patients with known QT prolongation or in combination with other drugs that are inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, voriconazole), or known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic…
CYP3A4 Inhibitors: Consider RALDESY dose reduction based on tolerability ( 2.5 , 7 ).
Strong CYP3A4 Inhibitors Clinical Impact: The concomitant use of RALDESY and strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of RALDESY alone.
Intervention: If RALDESY is used with a potent CYP3A4 inhibitor, the risk of adverse reactions, including cardiac arrhythmias, may be increased and a lower dose of RALDESY should be considered [see Dosage and Administration (2.5) , Warnings and Precautions (5.3) ].
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.