What the FDA labels say about taking them together
Fluconazole and methadone
Fluconazole's FDA label (Fluconazole) of April 2, 2026 names methadone in its drug interactions section, and methadone's label names fluconazole too. The methadone label: “Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6. …”
Check it at the source: the fluconazole FDA label on DailyMed (effective April 7, 2026, Zydus Pharmaceuticals (USA) Inc.); the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC).
What does the fluconazole label say about methadone?
Fluconazole label (Mylan Pharmaceuticals Inc., April 2, 2026), drug interactionsMethadone Fluconazole may enhance the serum concentration of methadone.
Source: FDA drug label (Fluconazole, NDA020090), Mylan Pharmaceuticals Inc., effective April 2, 2026 (SPL set 737e0fac-a2d2-4053-a0d7-edbfb6248f69), via openFDA
Source: FDA drug label (fluconazole), Zydus Pharmaceuticals (USA) Inc., effective April 7, 2026 (SPL set d1364455-1537-46d4-b093-38cca3be778f), via openFDA; the full label on DailyMed
What does the methadone label say about fluconazole?
Methadone label, drug interactionsClinical Impact: The concomitant use of methadone hydrochloride tablets and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration of methadone, resulting in decreased efficacy or onset of withdrawal symptoms in patients physically dependent on methadone. … Intervention: If concomitant use is necessary, consider increasing the methadone hydrochloride tablets dosage until stable drug effects are achieved. Assess for signs of opioid withdrawal. …
Diskets label (Hikma Pharmaceuticals USA Inc., December 1, 2025), drug interactionsMacrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine).
Methadose label (SpecGx LLC, April 27, 2026), drug interactionsInhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 Clinical Impact: Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6. The concomitant use of methadone and CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitors can increase the plasma concentration of methadone, resulting in increased or prolonged opioid … (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine)
Source: FDA drug label (Diskets, NDA017058), Hikma Pharmaceuticals USA Inc., effective December 1, 2025 (SPL set e6af84de-cbfc-4a3b-bd73-6bcf77337168), via openFDA
Source: FDA drug label (Methadose, NDA017116), SpecGx LLC, effective April 27, 2026 (SPL set 808a9d0b-720b-4034-a862-5122ff514608), via openFDA
Source: FDA drug label (Methadone Hydrochloride, NDA021624), Mylan Institutional LLC, effective December 31, 2025 (SPL set 092d78eb-6423-495c-bf0d-e6532bea7138), via openFDA
Source: FDA drug label (Methadone Hydrochloride), Epic Pharma, LLC, effective December 8, 2025 (SPL set 6da7501b-b881-4bc7-891a-74214a00a3ac), 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
| Fluconazole | Methadone | |
|---|---|---|
| Labeled for | Fungal infections, Urinary tract infections | Pain, Opioid use disorder |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.380 per tablet 200 mg tablet | $0.177 per tablet 10 mg tablet |
| 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