What the FDA labels say about taking them together
Acetaminophen/benzhydrocodone and ketoconazole
Acetaminophen/benzhydrocodone's FDA label of January 7, 2025 names ketoconazole in its drug interactions section; the ketoconazole label PlainMeds reads does not name acetaminophen/benzhydrocodone. The acetaminophen/benzhydrocodone label: “The concomitant use of APADAZ and CYP3A4 inducers can decrease the plasma concentration of hydrocodone, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical …”
Check it at the source: the acetaminophen/benzhydrocodone FDA label on DailyMed (effective January 7, 2025, Zevra Therapeutics, Inc.); the ketoconazole FDA label on DailyMed (effective January 28, 2026, E. Fougera & Co. a division of Fougera Pharmaceuticals, LLC).
What does the acetaminophen/benzhydrocodone label say about ketoconazole?
Acetaminophen/benzhydrocodone label, drug interactionsCYP3A4 Inducers Clinical Impact: The concomitant use of APADAZ and CYP3A4 inducers can decrease the plasma concentration of hydrocodone, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone. … Intervention: If concomitant use is necessary, consider increasing the APADAZ dosage until stable drug effects are achieved [see Dosage and Administration ( 2 )]. Assess for signs of opioid withdrawal. …
Acetaminophen/benzhydrocodone label, warnings and precautionsUse or Discontinuation of Cytochrome P450 CYP3A4 Inhibitors and Inducers Concomitant use of APADAZ 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 and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see Warnings and Precautions ( 5.3 )], particularly when an inhibitor is added after a stable dose of APADAZ is achieved.
Source: FDA drug label (APADAZ), Zevra Therapeutics, Inc., effective January 7, 2025 (SPL set 0590d4e5-7107-4015-a6a8-deac14265aa2), via openFDA; the full label on DailyMed
What does the ketoconazole label say about acetaminophen/benzhydrocodone?
Ketoconazole's label (effective January 28, 2026) does not name acetaminophen/benzhydrocodone in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (ketoconazole), E. Fougera & Co. a division of Fougera Pharmaceuticals, LLC, effective January 28, 2026 (SPL set cad7c647-34a9-4e4e-83b3-8d78e58f588f), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Acetaminophen/benzhydrocodone | Ketoconazole | |
|---|---|---|
| Labeled for | Pain | Fungal infections |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | n/a | $0.249 per gram 2% cream |
| Shortage now | No current entry | No current entry |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once