Darunavir and cobicistat and Fentanyl interaction

Darunavir and cobicistat and Fentanyl: 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 Darunavir and cobicistat (PREZCOBIX) label · effective 2026-02-01

Major

Narcotic analgesics metabolized by CYP3A: e.g. fentanyl, oxycodone ↑ fentanyl ↑ oxycodone Careful monitoring of therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with co-administration. tramadol ↑ tramadol A dose decrease may be needed for tramadol…

Drug interactionsnames FentanylView label on DailyMed
Major

…elbasvir/grazoprevir Lipid modifying agents: lomitapide, lovastatin, simvastatin Opioid Antagonist: naloxegol PDE-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension Sedatives/hypnotics: orally administered midazolam, triazolam PREZCOBIX or PREZCOBIX PED is contraindicated in patients receiving certain co-administered drugs for which altered plasma…

Contraindicationsby drug classView label on DailyMed
Major

Opioid Antagonist naloxegol ↑ naloxegol Co-administration of PREZCOBIX or PREZCOBIX PED and naloxegol is contraindicated due to potential for precipitating opioid withdrawal symptoms.

Drug interactionsby drug classView label on DailyMed
Major

Sedatives/hypnotics: orally administered midazolam, triazolam ↑ midazolam ↑ triazolam Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression.

Drug interactionsby drug classView label on DailyMed
Moderate

Narcotic analgesic for treatment of opioid dependence: buprenorphine, buprenorphine/naloxone, methadone buprenorphine or buprenorphine/ naloxone: effects unknown methadone: effects unknown Initiation of buprenorphine, buprenorphine/naloxone or methadone in patients taking PREZCOBIX or PREZCOBIX PED : Carefully titrate the dose of buprenorphine, buprenorphine/naloxone…

Drug interactionsby drug classView label on DailyMed

From the Fentanyl (FENTANYL CITRATE) label · effective 2026-04-07

Major

• Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl.

Boxed warningby drug classView label on DailyMed
Major

Cytochrome P450 3A4 Interaction The concomitant use of Fentanyl Citrate Injection with all cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.

Boxed warningby drug classView label on DailyMed
Major

Monitor patients receiving Fentanyl Citrate Injection and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.4) , Drug Interactions (7) , Clinical Pharmacology (12.3) ] .

Boxed warningby drug classView label on DailyMed
Moderate

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers Concomitant use of Fentanyl Citrate Injection with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of fentanyl and prolong…

Warnings and precautionsby drug classView label on DailyMed
Moderate

When using Fentanyl Citrate Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in Fentanyl Citrate Injection-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of Fentanyl Citrate Injection [see Dosage and Administration (2.1) , Drug Interactions (7) ] .

Warnings and precautionsby drug classView label on DailyMed

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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.