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Drug Interactions between Dura-Dumone and pitolisant

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

testosterone pitolisant

Applies to: Dura-Dumone (estradiol / testosterone) and pitolisant

MONITOR: Coadministration with pitolisant may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. Pitolisant is a borderline/weak inducer of CYP450 3A4. When studied with midazolam, a probe substrate for CYP450 3A4, pitolisant was found to reduce midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by less than 25%.

MANAGEMENT: Caution is advised when pitolisant is used in combination with sensitive CYP450 3A4 substrates. Clinical and laboratory monitoring may be appropriate whenever pitolisant is added to or withdrawn from therapy, and dosage adjustments made if necessary. It may be advisable to avoid concomitant use of pitolisant and CYP450 3A4 substrates with a narrow therapeutic index, if possible.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2019) "Product Information. Wakix (pitolisant)." Harmony Biosciences, LLC

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Drug and food interactions

Minor

estradiol food

Applies to: Dura-Dumone (estradiol / testosterone)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T (1995) "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet, 20, p. 219-24

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.