Does Hydrocodone Acetaminophen Interact With Ketoconazole?

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers Concomitant use of hydrocodone bitartrate and acetaminophen tablets 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 hydrocodone bitartrate and acetaminophen tablets and prolong opioid adverse reactions, and which may cause potentially fatal respirato…

Severity: Moderate

Severity basis: warnings section (keywords: may increase). Combining Hydrocodone Acetaminophen (Opioid analgesic combination) and Ketoconazole (Azole antifungal (strong CYP3A4 inhibitor)) is classified as a moderate interaction.

What to Do

Use this combination with caution. Your prescriber may monitor you more closely or adjust doses.

From the FDA Label

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers Concomitant use of hydrocodone bitartrate and acetaminophen tablets 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 hydrocodone bitartrate and acetaminophen tablets and prolong opioid adverse reactions, and which may cause potentially fatal respirato…

Source: FDA structured product labeling (set_id ee248dfd-7aa7-7dcc-e053-2995a90af19f).

Hydrocodone Acetaminophen

Opioid analgesic combination

Brands: Norco, Vicodin, Lortab

View Hydrocodone Acetaminophen safety profile

Ketoconazole

Azole antifungal (strong CYP3A4 inhibitor)

Brands: Nizoral

View Ketoconazole safety profile

Check these against your full medication list in our free Interaction Checker

This information is educational — not medical advice.

This page is provided for general educational purposes and summarizes publicly available data from sources such as the U.S. Food & Drug Administration. It is not a substitute for the judgment of a licensed clinician and should not be used to start, stop, or change any medication. It may be incomplete or out of date, and individual circumstances vary. Always talk with your prescriber or pharmacist about your specific medications and health conditions. If you think you may have a medical emergency, call 911.

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