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PCE Dispertab and Quetiapine Fumarate Tablets

Determining the interaction of PCE Dispertab and Quetiapine Fumarate Tablets and the possibility of their joint administration.

Check result:
PCE Dispertab <> Quetiapine Fumarate Tablets
Relevance: 03.12.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Talk to your doctor before using QUEtiapine together with erythromycin. Combining these medications can significantly increase the blood levels and effects of QUEtiapine. You may be more likely to experience side effects such as dizziness; drowsiness; dry mouth; constipation; increased appetite; weight gain; increased blood sugar and cholesterol or triglyceride levels; cognitive and motor impairment; involuntary muscle movements involving the face, tongue, or other parts of the body; difficulty swallowing; low blood pressure (especially at the start of treatment or after a dose increase); blood pressure increases (reported in children and teenagers); irregular heart rhythm; and seizures. Let your doctor know if your condition changes or you experience increased side effects. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or fast or pounding heartbeats during treatment with these medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly 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. High plasma levels of quetiapine may increase the risk and/or severity of serious adverse effects such as extrapyramidal symptoms, tardive dyskinesia, hyperglycemia, dyslipidemia, hyperprolactinemia, 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. 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.

GENERALLY AVOID: There is some concern that quetiapine may have additive cardiovascular effects in combination with other drugs that are known to prolong the QT interval of the electrocardiogram, including saquinavir, azole antifungal agents, and macrolide or ketolide antibiotics. In clinical trials, quetiapine was not associated with a persistent increase in QT intervals, and there was no statistically significant difference between quetiapine and placebo in the proportions of patients experiencing potentially important changes in ECG parameters including QT, QTc, and PR intervals. However, QT prolongation and torsade de pointes have been reported during postmarketing use in cases of quetiapine overdose and in patients with risk factors such as underlying illness or concomitant use of drugs known to cause electrolyte imbalance or increase QT interval. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Concomitant use of quetiapine with potent CYP450 3A4 inhibitors that can also prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if coadministration is required. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. In addition, the dosage of quetiapine should be reduced due to CYP450 3A4 inhibition. The product labeling recommends a reduction to one-sixth of the original dosage. Following discontinuation of the CYP450 3A4 inhibitor, the dosage of quetiapine should be increased by 6-fold.

References
  • 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
  • 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
  • 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
  • Spina E, Scordo MG, D'Arrigo C "Metabolic drug interactions with new psychotropic agents." Fundam Clin Pharmacol 17 (2003): 517-38
  • Hantson P, Di Fazio V, Wallemacq P "Toxicokinetic interaction between quetiapine and antiretroviral therapy following quetiapine overdose." Drug Metab Lett 4 (2010): 7-8
  • Spina E, de Leon J "Metabolic drug interactions with newer antipsychotics: a comparative review." Basic Clin Pharmacol Toxicol 100 (2007): 4-22
  • "Product Information. Seroquel (quetiapine)." Zeneca Pharmaceuticals, Wilmington, DE.
  • DeVane CL, Nemeroff CB "Clinical pharmacokinetics of quetiapine - An atypical antipsychotic." Clin Pharmacokinet 40 (2001): 509-22
PCE Dispertab

Generic Name: erythromycin

Brand name: EES. Granules, EES-400 Filmtab, EryPed 200, EryPed 400, Ery-Tab, Erythrocin Lactobionate, Erythrocin Stearate Filmtab, PCE Dispertab, E. E. S, EryPed, Erythrocin, Erythromycin Filmtabs, Erythromycin Lactobionate - IV

Synonyms: PCE Dispertab (Oral), PCE, PCE (Oral)

Quetiapine Fumarate Tablets

Generic Name: quetiapine

Brand name: Seroquel, Seroquel XR

Synonyms: Quetiapine, QUEtiapine

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

Interaction with food and lifestyle