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Drug Interactions between olutasidenib and toremifene

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

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Interactions between your drugs

Moderate

toremifene olutasidenib

Applies to: toremifene and olutasidenib

MONITOR: Coadministration with olutasidenib may decrease the plasma concentrations of drugs that are substrates of CYP450 3A4. Based on in vitro studies, olutasidenib may increase clearance via induction of CYP450 3A4, resulting in decreased plasma concentrations of agents that are metabolized by the isoenzyme. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Caution is advised if olutasidenib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly sensitive substrates or those with a narrow therapeutic range. The prescribing information for olutasidenib recommends avoiding coadministration with CYP450 3A4 substrates for which minimal concentration changes may lead to therapeutic failure. If coadministration is required, clinical and laboratory monitoring may be appropriate whenever olutasidenib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.

References

  1. (2022) "Product Information. Rezlidhia (olutasidenib)." Rigel Pharmaceuticals

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Drug and food interactions

Moderate

toremifene food

Applies to: toremifene

GENERALLY AVOID: Coadministration with grapefruit juice may theoretically increase the plasma concentrations of toremifene. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit. Because toremifene is associated with dose- and concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

GENERALLY AVOID: Due to their estrogenic effect, isoflavones present in soy such as genistein and daidzein may stimulate breast tumor growth and antagonize the antiproliferative action of toremifene. Supportive data are derived primarily from in vitro and animal studies. In vitro, low concentrations of these phytoestrogens have been found to promote DNA synthesis and reverse the inhibitory effect of tamoxifen on oestrogen-dependent breast cancer cell proliferation. In contrast, high concentrations of genistein greater than 10 microM/L have been found to enhance tamoxifen effects by inhibiting breast cancer cell growth. It is not known if these high concentrations are normally achieved in humans. Plasma concentrations below 4 microM/L have been observed in healthy volunteers given a soy diet for one month or large single doses of genistein. These concentrations are comparable to the low plasma concentrations associated with tumor stimulation reported in animals. In a study of 155 female breast cancer survivors with substantially bothersome hot flashes, a product containing 50 mg of soy isoflavones (40% to 45% genistein; 40% to 45% daidzein; 10% to 20% glycitein) taken three times a day was found to be no more effective than placebo in reducing hot flashes. No toxicity or recurrence of breast cancer was reported during the 9-week study period.

MANAGEMENT: Until more information is available, patients treated with toremifene should consider avoiding the consumption of grapefruit juice and soy-containing products. Patients should be advised to contact their physician if they experience vaginal bleeding or potential signs of blood clots such as chest pain, shortness of breath, sudden loss of vision, and pain, redness or swelling in an extremity. Patients should seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.

References

  1. (2001) "Product Information. Fareston (toremifene)." Schering Corporation
  2. Therapeutic Research Faculty (2008) Natural Medicines Comprehensive Database. http://www.naturaldatabase.com

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Moderate

olutasidenib food

Applies to: olutasidenib

ADJUST DOSING INTERVAL: Coadministration with a high-fat meal may increase the plasma concentrations of olutasidenib. According to the product labeling, administration of a single 150 mg dose with a high-fat meal (approximately 800 to 1000 calories, with approximately 50% of those calories from fat) increased olutasidenib peak plasma concentration (Cmax) and systemic exposure (AUC) by 191% and 83%, respectively, in healthy subjects.

MANAGEMENT: Olutasidenib should be administered at about the same time each day, on an empty stomach at least 1 hour before or 2 hours after a meal.

References

  1. (2022) "Product Information. Rezlidhia (olutasidenib)." Rigel Pharmaceuticals

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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.