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Drug Interactions between cyclosporine and quetiapine

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

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Interactions between your drugs

Moderate

cycloSPORINE QUEtiapine

Applies to: cyclosporine and quetiapine

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 The patient recovered a week after quetiapine was withdrawn.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Pharmacologic response to quetiapine should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the quetiapine dosage adjusted as necessary.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. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  2. "Quetiapine for schizophrenia." Med Lett Drugs Ther 39 (1997): 117-8
  3. DeVane CL, Nemeroff CB "Clinical pharmacokinetics of quetiapine - An atypical antipsychotic." Clin Pharmacokinet 40 (2001): 509-22
  4. Spina E, Scordo MG, D'Arrigo C "Metabolic drug interactions with new psychotropic agents." Fundam Clin Pharmacol 17 (2003): 517-38
  5. Grimm SW, Richtand NM, Winter HR, Stams KR, Reele SB "Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics." Br J Clin Pharmacol 61 (2006): 58-69
  6. Spina E, de Leon J "Metabolic drug interactions with newer antipsychotics: a comparative review." Basic Clin Pharmacol Toxicol 100 (2007): 4-22
  7. Urichuk L, Prior TI, Dursun S, Baker G "Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions." Curr Drug Metab 9 (2008): 410-8
  8. Schulz-Du Bois C, Schulz-Du Bois AC, Bewig B, et al. "Major increase of quetiapine steady-state plasma concentration following co-administration of clarithromycin: confirmation of the pharmacokinetic interaction potential of quetiapine." Pharmacopsychiatry 41 (2008): 258-9
  9. Hantson P, Di Fazio V, Wallemacq P "Toxicokinetic interaction between quetiapine and antiretroviral therapy following quetiapine overdose." Drug Metab Lett 4 (2010): 7-8
View all 9 references

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Drug and food interactions

Moderate

cycloSPORINE food

Applies to: cyclosporine

GENERALLY AVOID: Administration with grapefruit juice (compared to water or orange juice) has been shown to increase blood concentrations of cyclosporine with a relatively high degree of interpatient variability. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

GENERALLY AVOID: Administration with red wine or purple grape juice may decrease blood concentrations of cyclosporine. In 12 healthy volunteers, 12 ounces total of a merlot consumed 15 minutes prior to and during cyclosporine administration (single 8 mg/kg dose of Sandimmune) decreased cyclosporine peak blood concentration (Cmax) and systemic exposure (AUC) by 38% and 30%, respectively, compared to water. The time to reach peak concentration (Tmax) doubled, and oral clearance increased 50%. Similarly, one study were 12 healthy patients were administered purple grape juice and a single dose of cyclosporine showed a 30% and a 36% decrease in cyclosporine systemic exposure (AUC) and peak blood concentration (Cmax), respectively. The exact mechanism of interaction is unknown but may involve decreased cyclosporine absorption.

MONITOR: Food has been found to have variable effects on the absorption of cyclosporine. There have been reports of impaired, unchanged, and enhanced absorption during administration with meals relative to the fasting state. The mechanisms are unclear. Some investigators found an association with the fat content of food. In one study, increased fat intake resulted in significantly increased cyclosporine bioavailability and clearance. However, the AUC and pharmacodynamics of cyclosporine were not significantly affected, thus clinical relevance of these findings may be minimal.

MANAGEMENT: Patients receiving cyclosporine therapy should be advised to either refrain from or avoid fluctuations in the consumption of grapefruits and grapefruit juice. Until more data are available, the consumption of red wine or purple grape juice should preferably be avoided or limited. All oral formulations of cyclosporine should be administered on a consistent schedule with regard to time of day and relation to meals so as to avoid large fluctuations in plasma drug levels.

References

  1. Honcharik N, Yatscoff RW, Jeffery JR, Rush DN "The effect of meal composition on cyclosporine absorption." Transplantation 52 (1991): 1087-9
  2. Ducharme MP, Provenzano R, Dehoornesmith M, Edwards DJ "Trough concentrations of cyclosporine in blood following administration with grapefruit juice." Br J Clin Pharmacol 36 (1993): 457-9
  3. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  4. Hollander AAMJ, Vanrooij J, Lentjes EGWM, Arbouw F, Vanbree JB, Schoemaker RC, Vanes LA, Vanderwoude FJ, Cohen AF "The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients." Clin Pharmacol Ther 57 (1995): 318-24
  5. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  6. Tan KKC, Trull AK, Uttridge JA, Metcalfe S, Heyes CS, Facey S, Evans DB "Effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine in kidney transplant recipients." Clin Pharmacol Ther 57 (1995): 425-33
  7. Yee GC, Stanley DL, Pessa LJ, et al. "Effect of grrapefruit juice on blood cyclosporin concentration." Lancet 345 (1995): 955-6
  8. Ducharme MP, Warbasse LH, Edwards DJ "Disposition of intravenous and oral cyclosporine after administration with grapefruit juice." Clin Pharmacol Ther 57 (1995): 485-91
  9. Ioannidesdemos LL, Christophidis N, Ryan P, Angelis P, Liolios L, Mclean AJ "Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases." J Rheumatol 24 (1997): 49-54
  10. Min DI, Ku YM, Perry PJ, Ukah FO, Ashton K, Martin MF, Hunsicker LG "Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients." Transplantation 62 (1996): 123-5
  11. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
  12. Tsunoda SM, Harris RZ, Christians U, et al. "Red wine decreases cyclosporine bioavailability." Clin Pharmacol Ther 70 (2001): 462-7
  13. Oliveira-Freitas VL, Dalla Costa T, Manfro RC, Cruz LB, Schwartsmann G "Influence of purple grape juice in cyclosporine availability." J Ren Nutr 20 (2010): 309-13
View all 13 references

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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.

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