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Drug Interactions between deferasirox and Revatio

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

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Interactions between your drugs

Moderate

sildenafil deferasirox

Applies to: Revatio (sildenafil) and deferasirox

MONITOR: Coadministration with deferasirox may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism may involve induction of CYP450 3A4 activity by deferasirox, although in vitro, the drug has been shown to inhibit CYP450 3A4. In healthy volunteers, administration of the CYP450 3A4 probe substrate midazolam in combination with deferasirox resulted in a reduction of midazolam peak concentration by 23% and systemic exposure by 17%. In the clinical setting, this effect may be more pronounced.

MANAGEMENT: Caution is advised if deferasirox must be used concomitantly with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever deferasirox is added to or withdrawn from therapy.

References

  1. (2005) "Product Information. Exjade (deferasirox)." Novartis Pharmaceuticals
  2. Skerjanec A, Wang J, Maren K, Rojkjaer L (2010) "Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers." J Clin Pharmacol, 50, p. 205-13

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Drug and food interactions

Moderate

sildenafil food

Applies to: Revatio (sildenafil)

GENERALLY AVOID: Coadministration with grapefruit juice may slightly increase the oral bioavailability and delay the onset of action of sildenafil. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In a randomized, crossover study with 24 healthy male volunteers, ingestion of 250 mL of grapefruit juice one hour before and concurrently with a 50 mg dose of sildenafil increased the mean area under the plasma concentration-time curve (AUC) of sildenafil and its pharmacologically active N-desmethyl metabolite by 23% and 24%, respectively, compared to water. Peak plasma concentrations (Cmax) were unaltered, but the time to reach sildenafil Cmax was prolonged by 0.25 hour. The observed increase in sildenafil bioavailability is unlikely to be of clinical significance in most individuals. However, pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability and may be significant in the occasional susceptible patient. Indeed, one subject in the study had a 2.6-fold increase in sildenafil concentrations.

MANAGEMENT: It may be advisable to avoid administration of sildenafil with grapefruit juice to prevent potential toxicity and delay in onset of action.

References

  1. Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. (2002) "Effects of grapefruit juice on the pharmacokinetics of sildenafil." Clin Pharmacol Ther, 71, p. 21-29

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Moderate

deferasirox food

Applies to: deferasirox

ADJUST DOSING INTERVAL: According to product labeling, the bioavailability of deferasirox was variably increased when taken with a meal.

MANAGEMENT: To ensure consistent plasma drug levels, deferasirox should be taken on an empty stomach 30 minutes before eating preferably at the same time everyday.

References

  1. (2005) "Product Information. Exjade (deferasirox)." Novartis 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.

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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