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Drug Interactions between Givlaari and Mintezol

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

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Interactions between your drugs

Moderate

thiabendazole givosiran

Applies to: Mintezol (thiabendazole) and Givlaari (givosiran)

MONITOR: Coadministration with givosiran may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of CYP450 1A2 and/or CYP450 2D6. The proposed mechanism is decreased clearance due to givosiran-mediated inhibition of CYP450 1A2 and 2D6 isoenzymes. Concomitant administration of a single subcutaneous dose of givosiran (2.5 mg/kg) increased the systemic exposure (AUC) and peak plasma concentration (Cmax) of caffeine (sensitive CYP450 1A2 substrate) by 3.1-fold and 1.3-fold, respectively, and dextromethorphan (sensitive CYP450 2D6 substrate) by 2.4-fold and 2.0-fold, respectively.

MANAGEMENT: Caution and monitoring are recommended when givosiran is given with drugs that are substrates of CYP450 1A2 and/or 2D6. Concomitant use should generally be avoided with CYP450 1A2 or 2D6 substrates that have a narrow therapeutic range where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, the dosage of the CYP450 1A2 or 2D6 substrate should be reduced according to approved product labeling or clinical response and tolerance. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever givosiran is added to or withdrawn from therapy with these drugs.

References (1)
  1. (2019) "Product Information. Givlaari (givosiran)." Alnylam Pharmaceuticals

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Drug and food interactions

Moderate

thiabendazole food

Applies to: Mintezol (thiabendazole)

MONITOR: Coadministration with thiabendazole may increase the plasma concentrations of caffeine. The mechanism is thiabendazole inhibition of the CYP450 1A2 metabolism of caffeine. In ten healthy, nonsmoking volunteers, administration of a single 136.5 mg dose of caffeine in combination with a single 500 mg dose of thiabendazole resulted in a nearly 60% increase in the area under the plasma concentration-time curve (AUC) of caffeine compared to administration without thiabendazole. In addition, the half-life of caffeine was increased from 11.9 to 28.6 hours, and oral clearance was reduced by 67% during coadministration with thiabendazole. The formation of paraxanthine from caffeine, which is primarily mediated by CYP450 1A2, was almost completely abolished until after the thiabendazole was cleared from the system.

MANAGEMENT: Patients should be advised that pharmacologic effects of caffeine may be increased during coadministration with thiabendazole.

References (1)
  1. Bapiro TE, Sayi J, Hasler JA, et al. (2005) "Artemisinin and thiabendazole are potent inhibitors of cytochrome P450 1A2 (CYP1A2) activity in humans." Eur J Clin Pharmacol, 61, p. 755-61

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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.