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Drug Interactions between imatinib and Seroquel XR

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

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Interactions between your drugs

Moderate

QUEtiapine imatinib

Applies to: Seroquel XR (quetiapine) and imatinib

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of quetiapine, which is primarily metabolized by the isoenzyme. In 12 healthy volunteers, administration of a single 25 mg dose of quetiapine with the potent CYP450 3A4 inhibitor ketoconazole (200 mg once daily for 4 days) increased mean quetiapine peak plasma concentration (Cmax) and systemic exposure (AUC) by 3.4- and 6.2-fold, respectively, and decreased mean oral clearance by 84% compared to quetiapine administered alone. A case report describes a patient treated with quetiapine 700 mg/day who developed severely impaired consciousness and respiratory depression requiring intensive care surveillance following two 500 mg doses of clarithromycin, another potent CYP450 3A4 inhibitor. Quetiapine plasma level was found to be nearly 5 times the high end of the recommended therapeutic range. The patient recovered a week after quetiapine was withdrawn. The interaction was also suspected in a case report of two patients receiving quetiapine with ritonavir-boosted atazanavir. One patient experienced significant increases in appetite and serum glucose and a weight gain of more than 22 kg over six months. The patient's weight returned to baseline five months after stopping both treatments. The second patient had increased sedation and mental confusion, which resolved several days following self-discontinuation of quetiapine.

MANAGEMENT: Pharmacologic response to quetiapine should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the quetiapine dosage adjusted as necessary. Patients should be monitored for potentially increased adverse effects such as dizziness, drowsiness, dry mouth, constipation, increased appetite, weight gain, extrapyramidal symptoms, tardive dyskinesia, hyperglycemia, dyslipidemia, hyperprolactinemia (galactorrhea, amenorrhea, gynecomastia), orthostatic hypotension, blood pressure increases (in children and adolescents), QT prolongation, cognitive and motor impairment, dysphagia, and heat-related illnesses due to disruption of body temperature regulation.

References

  1. (2001) "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals
  2. (1997) "Quetiapine for schizophrenia." Med Lett Drugs Ther, 39, p. 117-8
  3. DeVane CL, Nemeroff CB (2001) "Clinical pharmacokinetics of quetiapine - An atypical antipsychotic." Clin Pharmacokinet, 40, p. 509-22
  4. Spina E, Scordo MG, D'Arrigo C (2003) "Metabolic drug interactions with new psychotropic agents." Fundam Clin Pharmacol, 17, p. 517-38
  5. Grimm SW, Richtand NM, Winter HR, Stams KR, Reele SB (2006) "Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics." Br J Clin Pharmacol, 61, p. 58-69
  6. Spina E, de Leon J (2007) "Metabolic drug interactions with newer antipsychotics: a comparative review." Basic Clin Pharmacol Toxicol, 100, p. 4-22
  7. Urichuk L, Prior TI, Dursun S, Baker G (2008) "Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions." Curr Drug Metab, 9, p. 410-8
  8. Schulz-Du Bois C, Schulz-Du Bois AC, Bewig B, et al. (2008) "Major increase of quetiapine steady-state plasma concentration following co-administration of clarithromycin: confirmation of the pharmacokinetic interaction potential of quetiapine." Pharmacopsychiatry, 41, p. 258-9
  9. Hantson P, Di Fazio V, Wallemacq P (2010) "Toxicokinetic interaction between quetiapine and antiretroviral therapy following quetiapine overdose." Drug Metab Lett, 4, p. 7-8
View all 9 references

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Drug and food interactions

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.

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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