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Drug Interactions between albendazole and dabrafenib

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

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Interactions between your drugs

Moderate

albendazole dabrafenib

Applies to: albendazole and dabrafenib

MONITOR: Coadministration with dabrafenib may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4 and/or 2C9. Dabrafenib has been found in vitro to be an inducer of these isoenzymes. Onset of induction is likely to occur after 3 days of repeat dosing with dabrafenib; however, transient inhibition of CYP450 isoenzymes may be observed during the first few days of treatment. In 12 study subjects, administration of the CYP450 3A4 probe substrate midazolam following repeat doses of dabrafenib 150 mg twice daily for 15 days reduced midazolam peak plasma concentration (Cmax) by 61% and systemic exposure (AUC) by 74%. When a single 15 mg dose of warfarin was coadministered similarly with dabrafenib, the AUC of S(-) warfarin decreased by 37% and that of R(+) decreased by 33%. S(-) warfarin, the biologically more active enantiomer, is primarily metabolized by CYP450 2C9, while R(+) warfarin is a substrate of CYP450 3A4 and 1A2.

MANAGEMENT: Caution is advised when dabrafenib is prescribed with drugs that undergo metabolism by CYP450 3A4 and/or 2C9. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever dabrafenib is added to or withdrawn from therapy. Significantly reduced plasma concentrations and loss of efficacy may occur with sensitive substrates of CYP450 3A4 or 2C9 such as hormonal contraceptives, immunosuppressants (cyclosporine, everolimus, sirolimus, tacrolimus), ivacaftor, and warfarin-type anticoagulants. Alternatives to these medications should be considered if possible.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Tafinlar (dabrafenib)." GlaxoSmithKline

Drug and food interactions

Moderate

albendazole food

Applies to: albendazole

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of albendazole, which is rapidly converted by hepatocytes and intestinal mucosal cells into the active metabolite, albendazole sulfoxide (ABZSX), following absorption. The proposed mechanism is stimulation of gastric acid secretion, as the absorption of albendazole is thought to be pH-dependent. According to the product labeling, plasma concentrations of ABZSX are up to 5-fold higher on average when albendazole is administered with a fatty meal (fat content approximately 40 g) compared to administration in the fasted state. In one study of six healthy male volunteers, administration of a single 10 mg/kg oral dose of albendazole in combination with a high-fat meal (57 g fat, 1399 kcal) increased the mean ABZSX peak plasma concentration (Cmax) and systemic exposure (AUC) by 6.5- and 9.4-fold, respectively, and delayed the time to reach Cmax (Tmax) from 2.5 to 5.3 hours compared to administration in the fasted state with water. The elimination half-life was not affected.

MONITOR: Grapefruit juice may increase the oral bioavailability of albendazole, which is rapidly converted by hepatocytes and intestinal mucosal cells into the active metabolite, albendazole sulfoxide (ABZSX), following absorption. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In six healthy male volunteers, administration of a single 10 mg/kg oral dose of albendazole in combination with 250 mL of double-strength grapefruit juice increased the mean ABZSX peak plasma concentration (Cmax) and systemic exposure (AUC) by 3.2- and 3.1-fold, respectively, compared to administration with water. However, because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: To ensure maximal oral absorption, albendazole should be taken with food. Grapefruit juice may also enhance the oral bioavailability of albendazole.

References (3)
  1. Awadzi K, Hero M, Opoku NO, Buttner DW, Coventry PA, Prime MA, Orme ML, Edwards G (1994) "The chemotherapy of onchocerciasis XVII. A clinical evaluation of albendazole in patients with onchocerciasis; effects of food and pretreatment with ivermectin on drug response and pharmacokinetics." Trop Med Parasitol, 45, p. 203-8
  2. (2001) "Product Information. Albenza (albendazole)." SmithKline Beecham
  3. Nagy J, Schipper HG, Koopmans RP, Butter JJ, van Boxtel CJ, Kager PA (2002) "Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability." Am J Trop Med Hyg, 66, p. 260-3
Moderate

dabrafenib food

Applies to: dabrafenib

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of dabrafenib. In study subjects, administration of dabrafenib with a high-fat meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 31%, respectively, and delayed median Tmax by approximately 3.6 hours compared to administration in the fasted state.

MANAGEMENT: Dabrafenib should be taken at least 1 hour before or 2 hours after a meal.

References (1)
  1. (2013) "Product Information. Tafinlar (dabrafenib)." GlaxoSmithKline

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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