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Drug Interactions between mitapivat and Thioplex

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

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Interactions between your drugs

Moderate

thiotepa mitapivat

Applies to: Thioplex (thiotepa) and mitapivat

MONITOR: Coadministration with CYP450 3A4 and/or 2B6 inducers may decrease plasma concentrations of thiotepa and increase concentrations of its active metabolite triethylenephosphoramide (TEPA). Thiotepa is a prodrug that is primarily converted to TEPA by these isoenzymes. In a study involving a 42-year-old male with relapsing germ-cell cancer, the pharmacokinetics of thiotepa and its active metabolite (TEPA) were assessed during two high-dose chemotherapy courses (cyclophosphamide 1500 mg/m2/day, thiotepa 120 mg/m2/day, and carboplatin), with phenytoin initiated five days before the second course for seizure management. In the second course, TEPA exposure increased by 115% and thiotepa exposure decreased by 29%, resulting in a thiotepa dose reduction of nearly 40% on day 3 due to the increased risk of toxicity from higher TEPA exposure. Clinical data for thiotepa use in combination with other less potent CYP450 3A4 inducers or with CYP450 2B6 inducers are not available.

MANAGEMENT: Caution and closer monitoring for adverse effects is advised when thiotepa is used concurrently with CYP450 3A4 and/or 2B6 inducers. Patients should be more closely monitored for thiotepa-related toxicities such as myelosuppression, cutaneous toxicity, and neurotoxicity. A dosage reduction of thiotepa may be necessary. Pretreatment and subsequent blood counts may be used to guide dose adjustments in accordance with product labeling.

References (5)
  1. de Jonge ME, Huitema AD, van Dam SM, Beijnen JH, Rodenhuis S (2005) "Significant induction of cyclophosphamide and thiotepa metabolism by phenytoin." Cancer Chemother Pharmacol, 55, p. 507-10
  2. (2023) "Product Information. Thiotepa (thiotepa)." Meitheal Pharmaceuticals Inc.
  3. (2023) "Product Information. Tepadina (thiotepa)." Link Medical Products Pty Ltd T/A Link Pharmaceuticals, 3
  4. (2022) "Product Information. Thiotepa (thiotepa)." MSN Laboratories Europe Ltd
  5. (2021) "Product Information. Tepadina (thiotepa)." Adienne SA

Drug and food interactions

Major

mitapivat food

Applies to: mitapivat

GENERALLY AVOID: Theoretically, the coadministration with grapefruit juice may increase the plasma concentrations of mitapivat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. 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. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid or limit consumption of grapefruit or grapefruit juice during therapy with mitapivat if possible. If concomitant use is unavoidable, close monitoring of hemoglobin levels and for the development of adverse effects such as atrial fibrillation, gastroenteritis, rib fracture, musculoskeletal pain, arthralgia, increased urate levels, and in males, for decreased estrone and estradiol levels, is recommended. The product labeling should be consulted for dose adjustments of mitapivat in the event of the development of adverse reaction or hemoglobin levels above normal.

References (33)
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  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
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  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
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  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
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  33. (2022) "Product Information. Pyrukynd (mitapivat)." Agios Pharmaceuticals, Inc.

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.

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