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Drug Interactions between deferasirox and saquinavir

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

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Interactions between your drugs

Moderate

saquinavir deferasirox

Applies to: saquinavir 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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever deferasirox is added to or withdrawn from therapy.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

saquinavir food

Applies to: saquinavir

ADJUST DOSING INTERVAL: Food significantly increases the absorption of saquinavir.

MONITOR: Coadministration with grapefruit juice may increase the plasma concentrations of saquinavir. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In eight healthy volunteers, ingestion of 400 mL of grapefruit juice prior to administration of a 600 mg dose of saquinavir mesylate increased the area under the plasma concentration-time curve and oral bioavailability of saquinavir by 50% and 100%, respectively, compared to water; however, the increase is not considered clinically relevant. A high degree of intersubject variability in the grapefruit juice effect was also observed. The extent to which this interaction may occur with the saquinavir free base soft gelatin capsule is unknown. However, the saquinavir soft gelatin capsule formulation is no longer commercially available.

MANAGEMENT: Saquinavir mesylate should be taken with meals or within 2 hours after eating to enhance bioavailability. Patients should be advised to avoid the consumption of large amounts of grapefruit and grapefruit juice during saquinavir therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation.

References

  1. (2001) "Product Information. Invirase (saquinavir)." Roche Laboratories
  2. Kupferschmidt HHT, Fattinger KE, Ha HR, Follath F, Krahenbuhl S (1998) "Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man." Br J Clin Pharmacol, 45, p. 355-9
  3. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  4. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  6. Cerner Multum, Inc. "Australian Product Information."
View all 6 references

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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.


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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.