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What the FDA labels say about taking them together

Methadone and ritonavir

Methadone's FDA label of December 8, 2025 names ritonavir in its drug interactions section, and ritonavir's label names methadone 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 methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC); the ritonavir FDA label on DailyMed (effective July 23, 2026, AbbVie Inc.).

What does the methadone label say about ritonavir?

Methadone label, drug interactions

Clinical 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 interactions

Macrolide 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 interactions

Inhibitors 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 … 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)

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

What does the ritonavir label say about methadone?

Ritonavir label, drug interactions

Concomitant Drug Class/Drug Name: Analgesics, Opioid: tramadol, propoxyphene, methadone, fentanyl; Effect on Concentration of Ritonavir or Concomitant Drug: ↑ analgesics ↓ methadone ↑ fentanyl; Clinical Comment: A dose decrease may be needed for these drugs when co-administered with ritonavir. Dosage increase of methadone may be considered. Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl is concomitantly administered with NORVIR.

Source: FDA drug label (Norvir), AbbVie Inc., effective July 23, 2026 (SPL set 2849298e-de6e-47bb-8194-56e075b33fc3), 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

18Methadone generic labelers
7Ritonavir generic labelers
MethadoneRitonavir
Labeled forPain, Opioid use disorderHIV
Boxed warningYesYes
Pharmacy cost (NADAC)$0.177 per tablet 10 mg tablet$0.607 per tablet 100 mg tablet
Shortage nowNo current entryA presentation being discontinued

Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)

What next?