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Drug Interactions between deferasirox and erlotinib

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

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Interactions between your drugs

Moderate

erlotinib deferasirox

Applies to: erlotinib and deferasirox

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of erlotinib, which has been shown in vitro to be primarily metabolized by CYP450 3A4 (approximately 80% to 95%) and to a lesser extent by CYP450 1A2. According to the product labeling, erlotinib systemic exposure (AUC) was reduced in the presence of the potent inducer rifampin by 58% to 80%, which is equivalent to a dose of about 30 to 63 mg in lung cancer patients. In one study, pretreatment with rifampin 600 mg daily for 7 days prior to administration of a single 150 mg erlotinib dose increased clearance of erlotinib by 3-fold and reduced median AUC by 69% compared to erlotinib administered alone. In another study, pretreatment with rifampin for 11 days followed by a single 450 mg dose of erlotinib on day 8 resulted in a mean erlotinib AUC that was just 58% of that observed following a single 150 mg dose of erlotinib in the absence of rifampin treatment. Systemic exposure of the active metabolites of erlotinib (OSI-413 and OSI-420) was largely unaffected by rifampin. Consequently, the active metabolites represented 18% of the total erlotinib exposure following coadministration with rifampin relative to only 5% when erlotinib was given alone. No data are available for use with other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of erlotinib should be considered during coadministration with CYP450 3A4 inducers. Pharmacologic response to erlotinib should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the erlotinib dosage adjusted as necessary.

References

  1. Li J, Zhao M, He P, Hidalgo M, Baker SD (2007) "Differential metabolism of gefitinib and erlotinib by human cytochrome p450 enzymes." Clin Cancer Res, 13, p. 3731-7
  2. (2018) "Product Information. Tarceva (erlotinib)." Genentech
  3. (2018) "Product Information. Tarceva (erlotinib)." Hoffmann-La Roche Limited
  4. (2022) "Product Information. Tarceva (erlotinib)." Roche Products Ltd
  5. (2022) "Product Information. Tarceva (erlotinib)." Roche Products Pty Ltd
  6. Hamilton M, Wolf JL, Drolet DW, et al. (2014) "The effect of rifampicin, a prototypical CYP3A4 inducer, on erlotinib pharmacokinetics in healthy subjects" Cancer Chemother Pharmacol, 73, p. 613-21
View all 6 references

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Drug and food interactions

Moderate

erlotinib food

Applies to: erlotinib

GENERALLY AVOID: Grapefruit and grapefruit juice may increase the plasma concentrations of erlotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for ketoconazole, a potent CYP450 3A4 inhibitor that increased erlotinib systemic exposure (AUC) by 67%. In general, the effects of grapefruit products are concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (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.

GENERALLY AVOID: Cigarette smoking reduces erlotinib exposure due to induction of hepatic CYP450 1A2, one of the isoenzymes responsible for the metabolic clearance of erlotinib. Induction of CYP450 1A1 in the lungs may also contribute. In one pharmacokinetic study of healthy subjects given a single 150 mg dose of erlotinib, mean erlotinib peak plasma concentration (Cmax), systemic exposure (AUC) and plasma concentration at 24 hours were decreased by 35%, 64% and 88%, respectively, in current smokers compared to former/never smokers. Likewise, in a phase 3 non-small cell lung cancer (NSCLC) trial, the steady-state trough plasma concentrations of erlotinib in current smokers were approximately 2-fold less than in former/never smokers, accompanied by a 24% increase in apparent erlotinib plasma clearance. In a phase 1 dose-escalation study that analyzed the steady-state pharmacokinetics of erlotinib in current smokers with NSCLC, there was a dose-proportional increase in erlotinib exposure when the dose was increased from 150 mg to 300 mg, the maximum tolerated dose in the study population. Median steady-state trough plasma concentration at the 300 mg dose was approximately 3-fold higher than at the 150 mg dose. The clinical impact of smoking on erlotinib efficacy has not been studied.

ADJUST DOSING INTERVAL: Food enhances the oral absorption of erlotinib. According to the product labeling, administration with food increased the oral bioavailability of erlotinib from approximately 60% to almost 100% compared to administration in the fasting state.

MANAGEMENT: Consumption of grapefruit and grapefruit juice should be avoided or limited during treatment with erlotinib. Patients who currently smoke cigarettes are advised to stop smoking as soon as possible. If cigarette smoking is continued while taking erlotinib, the manufacturer recommends increasing the dosage of erlotinib by 50 mg increments at 2-week intervals up to a maximum of 300 mg as tolerated. However, the efficacy and long-term safety of dosages higher than 150 mg daily have not been established. Data from a double-blind, randomized phase 3 study (MO22162, CURRENTS) demonstrated no benefit in progression free survival or overall survival with an erlotinib dosage of 300 mg daily relative to the recommended dosage of 150 mg daily in active smokers (average of 38 pack years) with locally advanced or metastatic NSCLC who have failed chemotherapy, although patients in the study were not selected based on epidermal growth factor receptor (EGFR) mutation status. Safety data were comparable between the two dosages, but a numerical increase in the incidence of rash, interstitial lung disease and diarrhea was observed with the higher dosage. Patients who have received a dosage increase should immediately revert to the recommended dosage of 150 mg or 100 mg once daily (depending on indication) upon cessation of smoking. Erlotinib should be administered on an empty stomach at least one hour before or two hours after the ingestion of food.

References

  1. (2018) "Product Information. Tarceva (erlotinib)." Genentech
  2. (2018) "Product Information. Tarceva (erlotinib)." Hoffmann-La Roche Limited
  3. (2022) "Product Information. Tarceva (erlotinib)." Roche Products Ltd
  4. (2022) "Product Information. Tarceva (erlotinib)." Roche Products Pty Ltd
View all 4 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.