Drug interactions
Difelikefalin + Tramadol
Severity: Moderate
Difelikefalin and Tramadol: 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 that can still cause somnolence and dizziness. Combined with tramadol, CNS depression may be additive. Risk is greater in dialysis patients, who have reduced clearance of many drugs.
What this interaction means in plain words
Difelikefalin and Tramadol 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; Tramadol belongs to Musculoskeletal.
Why it happens
Additive CNS depressant effects of kappa-opioid agonism and mu-opioid agonism.
What to do
Monitor for excess sedation, dizziness and respiratory depression, especially after starting or raising doses. Reduce the tramadol dose if sedation develops.
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 Tramadol
- Isocarboxazid + Tramadol Contraindicated
- Olanzapine / samidorphan + Tramadol Contraindicated
- Phenelzine + Tramadol Contraindicated
- Procarbazine + Tramadol Contraindicated
- Rasagiline + Tramadol Contraindicated
- Safinamide + Tramadol 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 Tramadol?
MediHelp rates the interaction as moderate. Difelikefalin and Tramadol 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 that can still cause somnolence and dizziness. Combined with tramadol, CNS depression may be additive. Risk is greater in dialysis patients, who have reduced clearance of many drugs.
How serious is the interaction between Difelikefalin and Tramadol?
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 excess sedation, dizziness and respiratory depression, especially after starting or raising doses. Reduce the tramadol dose if sedation develops.
What other medicines interact with Tramadol?
MediHelp also lists interactions of Tramadol with, for example, Isocarboxazid, Olanzapine / samidorphan, Phenelzine. The full list is on the Tramadol page.
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