Drug interactions
Difelikefalin + Methadone
Severity: Moderate
Difelikefalin and Methadone: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Difelikefalin is a peripherally restricted kappa-opioid agonist, and somnolence and dizziness are reported with it. Combined with methadone, additive sedation is possible, although the effect is usually modest.
What this interaction means in plain words
Difelikefalin and Methadone can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Difelikefalin belongs to Dermatology; Methadone belongs to Musculoskeletal.
Why it happens
Additive sedative effects from opioid receptor activity (mu agonism from methadone, kappa agonism from difelikefalin).
What to do
Monitor for drowsiness and dizziness, especially in patients on dialysis. Reduce doses if excess sedation occurs.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Methadone
- Alvimopan + Methadone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Methadone Contraindicated
- Droperidol + Methadone Contraindicated
- Ibutilide + Methadone Contraindicated
- Isocarboxazid + Methadone Contraindicated
- Lefamulin + Methadone Contraindicated
Other interactions of Difelikefalin
- Acetazolamide + Difelikefalin Moderate
- Alprazolam + Difelikefalin Moderate
- Amantadine + Difelikefalin Moderate
- Amitriptyline + Difelikefalin Moderate
- Amobarbital + Difelikefalin Moderate
- Asenapine + Difelikefalin Moderate
Frequently asked questions
Can I take Difelikefalin with Methadone?
MediHelp rates the interaction as moderate. Difelikefalin and Methadone can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Difelikefalin is a peripherally restricted kappa-opioid agonist, and somnolence and dizziness are reported with it. Combined with methadone, additive sedation is possible, although the effect is usually modest.
How serious is the interaction between Difelikefalin and Methadone?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for drowsiness and dizziness, especially in patients on dialysis. Reduce doses if excess sedation occurs.
What other medicines interact with Methadone?
MediHelp also lists interactions of Methadone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Droperidol. The full list is on the Methadone page.
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