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Drug Interactions between imatinib and Jalyn

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

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Interactions between your drugs

Moderate

tamsulosin imatinib

Applies to: Jalyn (dutasteride / tamsulosin) and imatinib

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or 2D6 may increase the plasma concentrations of tamsulosin, which is primarily metabolized in the liver by these isoenzymes. In 24 healthy volunteers, administration of a single 0.4 mg dose of tamsulosin with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily for 5 days) resulted in a 2.2-fold increase in tamsulosin peak plasma concentration (Cmax) and a 2.8-fold increase in systemic exposure (AUC) compared to administration alone. Likewise, concomitant treatment with the potent CYP450 2D6 inhibitor paroxetine (20 mg once daily for 9 days) resulted in an increase in the Cmax and AUC of a single 0.4 mg dose of tamsulosin by a factor of 1.3 and 1.6, respectively. The effects of concomitant administration of a moderate CYP450 3A4 inhibitor such as erythromycin or a moderate CYP450 2D6 inhibitor such as terbinafine on the pharmacokinetics of tamsulosin have not been evaluated. The effects of coadministration of both a CYP450 3A4 and a CYP450 2D6 inhibitor have also not been evaluated. However, there is a potential for significant increase in tamsulosin exposure relative to coadministration with either inhibitor alone. Similarly, a significant increase in exposure may occur when tamsulosin is administered with a CYP450 3A4 inhibitor to individuals who have genetic polymorphisms of CYP450 2D6 resulting in reduced or absent enzyme activity, or so-called CYP450 2D6 poor metabolizers (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent).

MANAGEMENT: Caution is advised if tamsulosin is used concomitantly with moderate CYP450 3A4 inhibitors (e.g., amiodarone, aprepitant, diltiazem, dronedarone, erythromycin, fluconazole, fluvoxamine, fusidic acid, imatinib, isavuconazonium, verapamil) and/or moderate to potent CYP450 2D6 inhibitors (e.g., abiraterone, bupropion, celecoxib, cinacalcet, darifenacin, dronedarone, duloxetine, fluoxetine, lorcaserin, paroxetine, propafenone, quinidine, ranolazine, rolapitant, terbinafine), particularly at a dosage higher than 0.4 mg/day. The potential for increased risk of adverse effects such as postural hypotension, syncope, and priapism should be considered. It should be noted that rolapitant, a moderate CYP450 2D6 inhibitor, can increase plasma concentrations and the risk of adverse effects of tamsulosin for at least 28 days after administration of rolapitant. Patients should be advised to avoid rising abruptly from a sitting or recumbent position, and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medication affects them.

References

  1. (2001) "Product Information. Flomax (tamsulosin)." Boehringer-Ingelheim
  2. Franco-Salinas G, de la Rosette JJ, Michel MC (2010) "Pharmacokinetics and pharmacodynamics of tamsulosin in its modified-release and oral controlled absorption system formulations." Clin Pharmacokinet, 49, p. 177-88
  3. Kamimura H, Oishi S, Matsushima H, et al. (1998) "Identification of cytochrome P450 isozymes involved in metabolism of the alpha1-adrenoceptor blocker tamsulosin in human liver microsomes." Xenobiotica, 28, p. 909-22
  4. (2015) "Product Information. Varubi (rolapitant)." Tesaro Inc.
View all 4 references

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Moderate

imatinib dutasteride

Applies to: imatinib and Jalyn (dutasteride / tamsulosin)

MONITOR: Based on in vitro data, coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of dutasteride, which is metabolized by the isoenzyme. No clinical drug interaction studies have been conducted. However, a population pharmacokinetic analysis found decreased clearance of dutasteride when it is coadministered with the moderate CYP450 3A4 inhibitors, verapamil and diltiazem (37% and 44%, respectively). In contrast, no decrease in dutasteride clearance was seen during coadministration with amlodipine, a calcium channel blocker that is not a CYP450 3A4 inhibitor.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of dutasteride should be considered during concomitant therapy with CYP450 3A4 inhibitors, particularly potent ones like itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics.

References

  1. (2002) "Product Information. Duagen (dutasteride)." GlaxoSmithKline Healthcare

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Drug and food interactions

Moderate

tamsulosin food

Applies to: Jalyn (dutasteride / tamsulosin)

ADJUST DOSING INTERVAL: Food may delay the gastrointestinal absorption of tamsulosin. The time to maximum plasma concentration (Tmax) is reached by 4 to 5 hours under fasted conditions and by 6 to 7 hours when tamsulosin is administered with food. The delay in Tmax has the desirable effect of smoothing the tamsulosin plasma concentration profile, thereby reducing fluctuation of the plasma peak and trough concentrations with multiple dosing. Food may also affect the extent of absorption of tamsulosin. It has been reported that taking tamsulosin under fasted conditions results in a 30% increase in bioavailability (AUC) and 40% to 70% increase in peak plasma concentration (Cmax) compared to fed conditions. The effects of food on the pharmacokinetics of tamsulosin are consistent regardless of whether tamsulosin is taken with a light meal or a high-fat meal.

MANAGEMENT: To ensure uniformity of absorption, tamsulosin should be administered approximately one-half hour following the same meal each day.

References

  1. (2001) "Product Information. Flomax (tamsulosin)." Boehringer-Ingelheim

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Moderate

imatinib food

Applies to: imatinib

GENERALLY AVOID: Coadministration of imatinib with strong CYP450 3A4 inhibitors such as grapefruit juice, may significantly increase the plasma concentrations of imatinib, a known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of imatinib by certain compounds present in grapefruits. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. In a single-dose study, coadministration of imatinib with ketoconazole (a strong CYP450 3A4 inhibitor) increased imatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 26% and 40%, respectively.

MANAGEMENT: Patients treated with imatinib should preferably avoid the consumption of grapefruit or grapefruit juice. If coadministration is unavoidable, monitor for prolonged and/or increased pharmacologic effects of imatinib, including edema, hematologic toxicity and immunosuppression.

References

  1. (2022) "Product Information. Gleevec (imatinib)." Novartis Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."

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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.