Q - Clinical Tree

Quetiapine — (Seroquel)

International Brand Names

Seroquel (Ecuador, England, Hong Kong, Hungary, Indonesia, Ireland, Israel, Korea, Malaysia, Netherlands, Philippines, Poland, Singapore, South Africa, Taiwan, Thailand); Socalm (India)

Drug Class	Antipsychotics
Indications	Psychosis
Mechanism	Unknown; antagonizes multiple neurotransmitter receptors
Dosage With Qualifiers	Psychosis—begin 25 mg PO bid, increase by 25–50 mg/dose q1–2 d; max 800 mg/d NOTE: Hepatic dosing. Contraindications —hypersensitivity to drug or class Caution —hepatic dysfunction, cardiac disease, CVD, seizures, hypotension, hypovolemia
Maternal Considerations	Quetiapine is a dibenzothiazepine derivative and considered an atypical antipsychotic agent. Among 1,522,247 pregnancies, the prevalence of use of second-generation antipsychotics at any time during pregnancy increased threefold, from 0.4% to 1.3%, over the 10-y period, while the use of first-generation antipsychotics remained stable at around 0.1%. The increased use of second-generation antipsychotics was largely driven by more frequent use among patients with bipolar disorder. Quetiapine and aripiprazole were the most frequently used, and polytherapy with antidepressants (65.2%), benzodiazepines (24.9%), and other mood stabilizers (22.0%) was common. More than 50% of women receiving an antipsychotic in the 3 mo prior to pregnancy discontinued the drug during pregnancy. Serum levels of quetiapine decline by more than 70% over the course of pregnancy and must be monitored. There is no evidence quetiapine increases the risk of adverse outcomes, though the published experience is limited. *Side effects* include hypotension, tardive dyskinesia, menstrual irregularities, hyperprolactinemia, hypothyroidism, diabetes mellitus, neuroleptic malignant syndrome, leukopenia, headache, somnolence, dizziness, constipation, tachycardia, dry mouth, asthenia, rash, hypercholesterolemia, hypertriglyceridemia, elevated LFTs, dyspepsia, abdominal pain, rhinitis, weight gain, and fever.
Fetal Considerations	There are no adequate reports or well-controlled studies in human fetuses. Quetiapine crosses the human placenta, achieving an F:M ratio of about 0.25. Only about 4% of the maternal dose is transferred across the isolated cotyledon. The pregnancy outcomes of women who contacted a teratogen information service after exposure to quetiapine appeared normal. In a systematic review of nine studies, 16 malformations were reported in 443 exposed pregnancies, resulting in a malformation rate of 3.6% and a relative risk of 1. Rodent studies are mostly reassuring, revealing no evidence of teratogenicity despite the use of doses higher than those used clinically. Embryotoxicity and IUGR were noted at the highest doses. Neonates exposed to antipsychotic drugs during the third trimester are at increased risk of withdrawal.
Breastfeeding Safety	There are no adequate reports or well-controlled studies in nursing women. Small amounts of quetiapine are excreted into human breast milk; the relative infant dose is estimated to be between 0.07% and 0.1%. No adverse effects are noted.
Drug Interactions	Potentiates the cognitive and motor effects of ethanol. May enhance certain antihypertensive agents. May antagonize the effects of levodopa and dopamine agonists. Phenytoin (100 mg tid) increases the oral clearance of quetiapine fivefold, requiring an increased dose of quetiapine to maintain control of symptoms of schizophrenia in patients receiving both quetiapine and phenytoin, or other hepatic enzyme inducers (e.g., barbiturates, carbamazepine, glucocorticoids, rifampin ). Divalproex (500 mg bid) increased the mean plasma concentration of quetiapine at steady state by 17% without affecting either the absorption or oral clearance. Thioridazine (200 mg bid) increased the oral clearance of quetiapine (300 mg bid) by 65%. Ketoconazole (200 mg qd × 4d), a potent inhibitor of CYP3A, reduced the oral clearance of quetiapine by 84%, resulting in a 335% increase in the maximum plasma concentration of quetiapine . Caution is indicated with ketoconazole and other CYP3A inhibitors (e.g., erythromycin, fluconazole, itraconazole ). The mean oral clearance of lorazepam (2 mg, single dose) was reduced by 20%.
References	Ennis ZN, Damkier P. Basic Clin Pharmacol Toxicol 2015; 116:315-20. Grover S, Madan R. J Neuropsychiatry Clin Neurosci 2012; 24:E38 Klier CM, Mossaheb N, Saria A, et al. J Clin Psychopharmacol 2007; 27:720-2. McKenna K, Koren G, Tetelbaum M, et al. J Clin Psychiatry 2005; 66:444-9. Misri S, Corral M, Wardrop AA, Kendrick K. J Clin Psychopharmacol 2006; 26:508-11. Newport DJ, Calamaras MR, DeVane CL, et al. Am J Psychiatry 2007; 164:1214-20. Park Y, Huybrechts KF, Cohen JM, et al. Psychiatr Serv 2017 Jun 15:appips201600408. [Epub ahead of print] Rahi M, Hekkinen T, Hartter S, et al. Psychopharmacol 2007; 21:751-6. Rampono J, Kristensen JH, Ilett KF, et al. Ann Pharmacother 2007; 41:711-4. Taylor TM, O’Toole MS, Ohlsen RI, et al. Am J Psychiatry 2003; 160:588-9. Tényi T, Nagy Á, Herold R, et al. Neuropsychopharmacol Hung 2013; 15:49-50. Tenyi T, Trixler M, Keresztes Z. Am J Psychiatry 2002; 159:674. Westin AA, Brekke M, Molden E, et al. Clin Pharmacol Ther 2017 Jun 23. [Epub ahead of print]
Summary	Pregnancy Category: C Lactation Category: S Quetiapine should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk. Quetiapine seems an agent of choice for breastfeeding women.