kwet-EYE-a-peen

Therapeutic Classification: antipsychotics

• Schizophrenia.
• Depressive episodes with bipolar disorder.
• Acute manic episodes associated with bipolar I disorder (as monotherapy [for adults or adolescents] or with lithium or divalproex [adults only]).
• Maintenance treatment of bipolar I disorder (with lithium or divalproex).
• Adjunctive treatment of depression.

• Probably acts by serving as an antagonist of dopamine and serotonin.
• Also antagonizes histamine H₁ receptors and alpha₁-adrenergic receptors.

• Decreased manifestations of psychoses, depression, or acute mania.

Absorption: Well absorbed after oral administration.

Distribution: Widely distributed.

Metabolism/Excretion: Extensively metabolized by the liver via the CYP3A4 isoenyzme to norquetiapine (active metabolite with anticholinergic properties); <1% excreted unchanged in the urine.

Half-life: 6 hr.

(antipsychotic effects)

Contraindicated in:

• Hypersensitivity
• Concurrent use of agents that prolong the QT interval, including dofetilide, sotalol, quinidine, disopyramide, amiodarone, dronedarone, thioridazine, chlorpromazine, droperidol, moxifloxacin, mefloquine, pentamidine, arsenic trioxide, tacrolimus, ziprasidone, erythromycin, citalopram, escitalopram, and clarithromycin (↑ risk of serious arrhythmias)
• History of arrhythmias, including bradycardia
• Hypokalemia or hypomagnesemia (↑ risk of serious arrhythmias)
• Congenital long QT syndrome (↑ risk of serious arrhythmias).

Use Cautiously in:

• Cardiovascular disease, cerebrovascular disease, dehydration, or hypovolemia (↑ risk of hypotension)
• History of seizures or Alzheimer’s dementia
• Diabetes (may ↑ risk of hyperglycemia)
• Patients at risk for aspiration pneumonia or falls
• Hepatic impairment (dose ↓ may be necessary)
• Hypothyroidism (may be exacerbated)
• History of suicide attempt
• Low white blood cell count or history of drug-induced leukopenia/neutropenia (↑ risk of leukopenia/neutropenia)
• Urinary retention, prostatic hypertrophy, constipation, or ↑ intraocular pressure
• OB: Neonates at ↑ risk for extrapyramidal symptoms and withdrawal after delivery when exposed during the 3rd trimester; use only if potential maternal benefit justifies potential fetal risk
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment; risk may be greater in children or adolescents
• Geri: Appears on Beers list. ↑ risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for schizophrenia, bipolar disorder, adjunctive treatment of major depressive disorder, or psychosis in Parkinson's disease.

CV: ↑BP (children), palpitations, peripheral edema, postural hypotension.

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), sweating.

EENT: ear pain, pharyngitis, rhinitis.

Endo: hyperglycemia, hyperprolactinemia, hypothyroidism.

GI: anorexia, constipation, dry mouth, dyspepsia, GI OBSTRUCTION, PANCREATITIS.

GU: ↓fertility (females).

Hemat: ↓hemoglobin, AGRANULOCYTOSIS, leukopenia, neutropenia.

Metab: weight gain, hyperlipidemia, hypertriglyceridemia.

MS: rhabdomyolysis.

Neuro: dizziness, cognitive impairment, extrapyramidal symptoms, NEUROLEPTIC MALIGNANT SYNDROME, sedation, SEIZURES, tardive dyskinesia.

Resp: cough, dyspnea.
Misc: flu-like syndrome.

Drug-Drug:

• QT interval prolonging medications, including macrolide antibiotics (erythromycin, clarithromycin), dofetilide, sotalol, quinidine, disopyramide, procainamide, thioridazine, chlorpromazine, droperidol, moxifloxacin, mefloquine, pentamidine, arsenic trioxide, citalopram, escitalopram, tacrolimus, and ziprasidone may ↑ the risk of serious ventricular arrhythmias and should be avoided.
• ↑CNS depression may occur with alcohol, antihistamines, opioid analgesics, and sedative/hypnotics.
• ↑risk of hypotension with acute ingestion of alcohol or antihypertensives.
• CYP3A inducers, including phenytoin, carbamazepine, barbiturates, rifampin, or corticosteroids may ↓ levels and effects.
• CYP3A inhibitors, including ketoconazole, itraconazole, fluconazole, protease inhibitors, or erythromycin may ↑ levels and risk of toxicity.
• Concurrent use of anticholinergic medications may ↑ risk of anticholinergic adverse reactions.

Schizophrenia

• PO (Adults): Immediate release: 25 mg twice daily on Day 1, ↑ by 25–50 mg 2–3 times daily on Days 2 and 3, up to 300–400 mg/day in 2–3 divided doses by Day 4 (not to exceed 800 mg/day); Extended release: 300 mg once daily, ↑ by 300 mg/day (not to exceed 800 mg/day); elderly patients or patients with hepatic impairment should be started on immediate-release product and converted to extended-release product once effective dose is reached.
• PO (Children 13–17 yr): Immediate release: 25 mg twice daily on Day 1, ↑ to 50 mg twice daily on Day 2, then ↑ to 100 mg twice daily on Day 3, then ↑ to 150 mg twice daily on Day 4, then ↑ to 200 mg twice daily on Day 5; may then ↑ by no more than 100 mg/day (not to exceed 800 mg/day).

Acute Manic Episodes Associated With Bipolar I Disorder

• PO (Adults): Immediate release: 50 mg twice daily on Day 1, then ↑ to 100 mg twice daily on Day 2, then ↑ to 150 mg twice daily on Day 3, then ↑ to 200 mg twice daily on Day 4; may then ↑ by no more than 200 mg/day up to 400 mg twice daily on Day 6 if needed; Extended release: 300 mg once daily on Day 1, then 600 mg once daily on Day 2, then 400–800 mg once daily starting on Day 3.
• PO (Children 10–17 yr): Immediate release: 25 mg twice daily on Day 1, then ↑ to 50 mg twice daily on Day 2, then ↑ to 100 mg twice daily on Day 3, then ↑ to 150 mg twice daily on Day 4, then ↑ to 200 mg twice daily on Day 5; may then ↑ by no more than 100 mg/day (not to exceed 600 mg/day).

Acute Depressive Episodes Associated With Bipolar Disorder

• PO (Adults): Immediate release or extended release: 50 mg once daily at bedtime on Day 1, then ↑ to 100 mg daily at bedtime on Day 2, then ↑ to 200 mg daily at bedtime on Day 3, then ↑ to 300 mg daily at bedtime thereafter.

Maintenance Treatment of Bipolar I Disorder

• PO (Adults): Continue at the dose required to maintain symptom remission (usual dosage: 400–800 mg/day given as once daily dose [extended release] or in two divided doses [immediate release]).
• PO (Children 10–17 yr): Continue at the lowest dose required to maintain symptom remission.

Depression

• PO (Adults): Extended release: 50 mg once daily on Days 1 and 2, then ↑ to 150 mg once daily starting on Day 3 (not to exceed 300 mg/day).

(Generic available)

• Immediate-release tablets: 25 mg; 50 mg; 100 mg; 200 mg; 300 mg; 400 mg;
• Extended-release tablets: 50 mg; 150 mg; 200 mg; 300 mg; 400 mg;

• Monitor mental status (mood, orientation, behavior) before and periodically during therapy.
• Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults 24 yr.
• Assess weight and BMI initially and during therapy.
• Monitor BP (sitting, standing, lying) and pulse before and frequently during initial dose titration. If hypotension occurs during dose titration, return to the previous dose.
• Observe patient carefully to ensure medication is swallowed and not hoarded or cheeked.
• Monitor for onset of extrapyramidal side effects (akathisia: restlessness; dystonia: muscle spasms and twisting motions; or pseudoparkinsonism: mask-like faces, rigidity, tremors, drooling, shuffling gait, dysphagia). Report these symptoms; reduction of dose or discontinuation may be necessary. Trihexyphenidyl or benztropine may be used to control these symptoms.
• Monitor for tardive dyskinesia (involuntary rhythmic movement of mouth, face, and extremities). Report immediately; may be irreversible.
• Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Notify health care professional immediately if these symptoms occur.
• Assess for rash periodically during therapy. May cause SJS. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
• Monitor for signs of pancreatitis (nausea, vomiting, anorexia, persistent severe abdominal pain, sometimes radiating to the back) during therapy.
• Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).
• Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.
• Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling), associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

• May cause asymptomatic ↑ in AST and ALT.
  • May also cause anemia, thrombocytopenia, leukocytosis, and leukopenia.
  • May cause ↑ total cholesterol and triglycerides.
  • Obtain fasting blood glucose and cholesterol levels initially and during therapy.
  • Monitor serum prolactin prior to and periodically during therapy. May cause ↑ serum prolactin levels.

• Do not confuse quetiapine with olanzapine. Do not confuse Seroquel with Seroquel XR.
• If therapy is reinstituted after an interval of 1 wk off, follow initial titration schedule.
• PO: May be administered without regard to food. DNC: Extended-release tablets should be swallowed whole, do not break, crush, or chew.

• Instruct patient to take medication as directed. Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Consult health care professional prior to stopping quetiapine; should be discontinued gradually. Stopping abruptly may cause insomnia, nausea, and vomiting.
• Advise patient and caregiver that quetiapine should not be given to elderly patients with dementia-related psychosis; may ↑ risk of death.
• Inform patient of the possibility of extrapyramidal symptoms. Instruct patient to report symptoms immediately to health care professional.
• Advise patient to change positions slowly to minimize orthostatic hypotension. Protect from falls.
• May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to avoid extremes in temperature; this drug impairs body temperature regulation.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications and alcohol, especially other CNS depressants, including opioids.
• Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking; other unusual changes in behavior or mood occur.
• Refer patient for nutritional, weight, or medical management of dyslipidemia as indicated.
• Advise patient to notify health care professional of medication regimen before treatment or surgery.
• Instruct patient to notify health care professional promptly of sore throat, fever, unusual bleeding or bruising, constipation, or rash.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during therapy. Encourage women who become pregnant while taking quetiapine to enroll in the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit womensmentalhealth.org/research/pregnancyregistry/. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. May lead to temporary, reversible infertility in females.
• Emphasize importance of routine follow-up exams to monitor side effects and continued participation in psychotherapy as indicated to improve coping skills. Ophthalmologic exams should be performed before and every 6 mo during therapy.

• Decrease in excited, manic, behavior.
• Decrease in signs of depression in patients with bipolar disorder.
• Decrease in manic episodes in patients with bipolar I disorder.
• Decrease in positive symptoms (delusions, hallucinations) of schizophrenia.
• Decrease in negative symptoms (social withdrawal, flat, blunt affect) of schizophrenia.

SEROquel, SEROquel XR