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What the FDA labels say about taking them together

Acetaminophen/benzhydrocodone and erythromycin

Acetaminophen/benzhydrocodone's FDA label of January 7, 2025 names erythromycin in its drug interactions section; the erythromycin labels PlainMeds reads (4) do 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 erythromycin FDA label on DailyMed (effective August 1, 2024, Teva Pharmaceuticals USA, Inc.).

What does the acetaminophen/benzhydrocodone label say about erythromycin?

Acetaminophen/benzhydrocodone label, drug interactions

CYP3A4 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 precautions

Use 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 erythromycin label say about acetaminophen/benzhydrocodone?

Erythromycin's label (effective August 1, 2024) and its 3 other brand-application labels do 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 (Erythromycin), Teva Pharmaceuticals USA, Inc., effective August 1, 2024 (SPL set 75a0bd5a-d09f-483b-bfd8-f8343b149eb2), 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

0Acetaminophen/benzhydrocodone generic labelers
38Erythromycin generic labelers
Acetaminophen/benzhydrocodoneErythromycin
Labeled forPainBacterial infections, Acne
Boxed warningYesNo
Pharmacy cost (NADAC)n/a$1.96 per tablet 250 mg tablet
Shortage nowNo current entryNo 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?