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Drug Interactions between palbociclib and quetiapine

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

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Interactions between your drugs

Moderate

QUEtiapine palbociclib

Applies to: quetiapine and palbociclib

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 The patient recovered a week after quetiapine was withdrawn.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Pharmacologic response to quetiapine should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the quetiapine dosage adjusted as necessary.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 (9)
  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

Drug and food interactions

Moderate

palbociclib food

Applies to: palbociclib

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the systemic exposure to palbociclib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Increased exposure to palbociclib may increase the risk of adverse effects such as infections, neutropenia, leukopenia, anemia, thrombocytopenia, anorexia, nausea, vomiting, diarrhea, stomatitis, alopecia, asthenia, peripheral neuropathy, and epistaxis.

ADJUST DOSING INTERVAL: Food may enhance the oral bioavailability of palbociclib capsules and reduce the intersubject variability of palbociclib exposure. According to the product labeling, absorption and exposure of palbociclib from its oral capsule formulation were very low in approximately 13% of the population when taken in the fasted state. Food intake increased the palbociclib exposure in this small subset of the population but did not alter exposure in the rest of the population to a clinically relevant extent. Compared to palbociclib capsules given under overnight fasted conditions, the population average palbociclib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 38% and 21%, respectively, when given with high-fat, high-calorie food (approximately 800 to 1000 calories; 150, 250, and 500 to 600 calories from protein, carbohydrate and fat, respectively); by 27% and 12%, respectively, when given with low-fat, low-calorie food (approximately 400 to 500 calories; 120, 250, and 28 to 35 calories from protein, carbohydrate and fat, respectively); and by 24% and 13%, respectively, when given with moderate-fat, standard calorie food (approximately 500 to 700 calories; 75 to 105, 250 to 350 and 175 to 245 calories from protein, carbohydrate and fat, respectively) one hour before and two hours after palbociclib capsule dosing.

MANAGEMENT: Patients should avoid consumption of grapefruit or grapefruit juice while on treatment with palbociclib. To avoid variability in drug absorption between doses, palbociclib capsules should be taken with food. Palbociclib tablet formulations may be taken with or without food.

References (4)
  1. (2020) "Product Information. Ibrance (palbociclib)." Pfizer Australia Pty Ltd, pfpibrac10620
  2. (2021) "Product Information. Ibrance (palbociclib)." Pfizer Canada Inc
  3. (2023) "Product Information. Ibrance (palbociclib)." Pfizer Ltd
  4. (2022) "Product Information. Ibrance (palbociclib)." Pfizer U.S. Pharmaceuticals Group

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

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