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Drug Interactions between Dolophine and nirogacestat

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

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Interactions between your drugs

Moderate

methadone nirogacestat

Applies to: Dolophine (methadone) and nirogacestat

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of methadone, which is metabolized primarily by CYP450 3A4, 2B6, 2C19, and to a lesser extent by CYP450 2C9 and 2D6. The possibility of prolonged and/or increased pharmacologic effects of methadone, such as central nervous system and respiratory depression, should be considered. In addition, high dosages (particularly above 200 mg/day) and serum levels of methadone have been associated with QT interval prolongation and torsade de pointes arrhythmia.

MANAGEMENT: Caution is advised if methadone is prescribed in combination with CYP450 3A4 inhibitors. Pharmacologic response to methadone should be closely monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of the CYP450 3A4 inhibitor in patients who are stabilized on their methadone regimen. Patients should be advised to report excessive drowsiness, nausea, or asthenia to their physician, and to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. ECG monitoring should be considered for patients on methadone with heart or liver disease; conduction abnormalities; electrolyte disturbances (i.e., hypokalemia, hypomagnesemia); concomitant use of drugs that may cause QT prolongation or electrolyte loss; concomitant use of CYP450 3A4 inhibitors; or use of methadone at dosages greater than 200 mg daily.

References

  1. Bell J, Seres V, Bowron P, Lewis J, Batey R "The use of serum methadone levels in patients receiving methadone maintenance." Clin Pharmacol Ther 43 (1988): 623-9
  2. Iribarne C, Berthou F, Baird S, Dreano Y, Picart D, Bail JP, Beaune P, Menez JF "Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes." Chem Res Toxicol 9 (1996): 365-73
  3. Oda Y, Kharasch ED "Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation." J Pharmacol Exp Ther 298 (2001): 1021-32
  4. Krantz MJ, Lewkowiez L, Hays H, et al. "Torsade de pointes associated with very-high-dose methadone." Ann Intern Med 137 (2002): 501-4
  5. Foster DJ, Somogyi AA, Bochner F "Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4." Br J Clin Pharmacol 47 (1999): 403-12
  6. Ehret GB, Desmeules JA, Broers B "Methadone-associated long QT syndrome: improving pharmacotherapy for dependence on illegal opioids and lessons learned for pharmacology." Expert Opin Drug Saf 6 (2007): 289-303
  7. Moody DE, Alburges ME, Parker RJ, Collings JM, Strong JM "The involvement of cytochrome P450 3A4 in the N-demethylation of L-alpha-acetylmethadol (LAAM), norLAAM, and methadone." Drug Metab Dispos 25 (1997): 1347-53
  8. "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences (2012):
View all 8 references

Drug and food interactions

Major

nirogacestat food

Applies to: nirogacestat

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit, grapefruit juice, Seville oranges, and starfruit may significantly increase the plasma concentrations and pharmacologic effects of nirogacestat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Coadministration of multiple doses of nirogacestat (150 mg twice daily) with the moderate CYP450 3A4 inhibitors erythromycin and fluconazole are predicted to increase the AUC of nirogacestat by 2.73-fold and 3.18-fold, respectively. The interaction has not been studied with grapefruit, Seville oranges, or starfruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to nirogacestat may increase the risk of adverse effects including diarrhea, ovarian toxicity, hepatotoxicity, electrolyte abnormalities, and non-melanoma skin cancers.

MANAGEMENT: Patients treated with nirogacestat should avoid consumption of grapefruit, grapefruit juice, Seville oranges, starfruit, or any supplement containing grapefruit.

References

  1. "Product Information. Ogsiveo (nirogacestat)." SpringWorks Therapeutics, Inc. (2023):
Moderate

methadone food

Applies to: Dolophine (methadone)

Grapefruit juice can increase the blood levels and effects of methadone. If you regularly consume grapefruits or grapefruit juice, you should be monitored for side effects and/or changes in methadone levels. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor. Orange juice is not expected to interact.

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Moderate

methadone food

Applies to: Dolophine (methadone)

Do not use alcohol or medications that contain alcohol while you are receiving treatment with methadone. This may increase nervous system side effects such as drowsiness, dizziness, lightheadedness, difficulty concentrating, and impairment in thinking and judgment. In severe cases, low blood pressure, respiratory distress, fainting, coma, or even death may occur. With certain long-acting formulations of narcotic pain medication, consumption of alcohol may also cause rapid release of the drug, resulting in high blood levels that may be potentially lethal. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. Do not use more than the recommended dose of methadone, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medication without first talking to your doctor.

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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.

See also

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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.

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