Nirmatrelvir and ritonavir and Tramadol interaction

Nirmatrelvir and ritonavir and Tramadol: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

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

Major

…voclosporin • Microsomal triglyceride transfer protein inhibitor: lomitapide • Migraine medications: eletriptan, ubrogepant • Mineralocorticoid receptor antagonists: finerenone • Non-opioid analgesic (selective blocker of Na v 1.8 sodium channels): suzetrigine • Opioid antagonists: naloxegol • PDE5 inhibitor: sildenafil (Revatio ® ) when used for pulmonary arterial…

Contraindicationsby drug classView label on DailyMed
Major

Opioid antagonists naloxegol ↑ naloxegol Co-administration contraindicated due to the potential for opioid withdrawal symptoms [see Contraindications (4) ] .

Drug interactionsby drug classView label on DailyMed
Major

Sedative/hypnotics triazolam, oral midazolam ↑ triazolam ↑ midazolam Co-administration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4) ] .

Drug interactionsby drug classView label on DailyMed
Major

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) ] .

Drug interactionsby drug classView label on DailyMed
Moderate

Narcotic analgesics fentanyl, hydrocodone, oxycodone, meperidine ↑ fentanyl ↑ hydrocodone ↑ oxycodone ↑ meperidine Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl, hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID.

Drug interactionsby drug classView label on DailyMed

From the Tramadol (Tramadol Hydrochloride Extended-Release) label · effective 2026-01-23

Major

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex.

Boxed warningby drug classView label on DailyMed
Major

Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with Tramadol Hydrochloride Extended-Release Capsules requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1.

Boxed warningby drug classView label on DailyMed
Major

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex.

Boxed warningby drug classView label on DailyMed
Major

Evaluate patients receiving Tramadol Hydrochloride Extended-Release Capsules and any CYP3A4 inhibitor or inducer at frequent intervals for the risk for serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity and opioid withdrawal when Tramadol Hydrochloride Extended-Release Capsules is used in conjunction…

Warnings and precautionsby drug classView label on DailyMed
Moderate

Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of Tramadol Hydrochloride Extended-Release Capsules and CYP3A4 inducers can decrease the plasma concentration of tramadol [see Clinical Pharmacology (12.3) ] , resulting…

Drug interactionsnames Nirmatrelvir and ritonavirView label on DailyMed

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

Open in the checker

Not 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.