Quetiapine

Quetiapine is available in the form of an Oral Tablet.

Quetiapine Tablet is taken orally, usually one to three times daily with or without food.

Quetiapine is an Antimanic Agent / Second Generation Antipsychotic agent belonging to Dopamine type 2 (D₂) and serotonin type 2 (5-HT₂) receptor antagonist class.

Quetiapine is a dibenzothiazepine atypical antipsychotic agent. Its clinical antipsychotic properties and low extrapyramidal side effect is mediated through a combination of D₂ and 5-HT₂ receptor antagonism. It has an affinity for serotonin (e.g. 5-HT₂), histamine (H₁) and adrenergic (e.g. α₁ and α₂) and dopamine (D₁ and D₂) receptors.

• Agitation/Aggression and psychosis associated with dementia, severe or refractory

Immediate release: Oral: Initial: 25 mg at bedtime; may increase the dose gradually (eg, weekly) based on response and tolerability up to 75 mg twice daily.

• Agitation and/or delirium, ICU

Immediate release: Oral or via NG tube: Initial: 50 mg twice daily; may increase based on response and tolerability in 100 mg increments at intervals ≥1 day up to a maximum dose of 400 mg/day. In patients who may be more sensitive to adverse effects, some experts start at 12.5 mg twice daily or 25 to 50 mg at bedtime and increase the dose more gradually (eg, in increments of 25 mg/day) based on response and tolerability.

• Bipolar disorder

Immediate release oral: Initial: 100 to 200 mg once daily at bedtime or in 2 divided doses on day 1, then increase by 100 mg/day (divided twice daily or as a single dose at bedtime) until 400 mg/day is reached by day 4; after that, may further increase based on response and tolerability in increments of ≤200 mg/day. According to some experts, the maximum dose is 800 mg/day; however, some patients may require amounts up to 1.2 g/day for optimal response.

Extended-release oral: Initial: 300 mg once daily on day 1; increase to 600 mg once daily on day 2, then adjust dose based on response and tolerability. Maximum dose: 800 mg once daily; however, some patients may require doses up to 1.2 g/day for optimal response.

• Delusional infestation

Immediate release oral: Initial: 12.5 to 50 mg at bedtime; gradually increase the dose based on response and tolerability every 3 to 7 days up to 200 to 300 mg at bedtime or in divided doses. Continue treatment for at least 3 months before attempting to decrease the dose.

• Generalized anxiety disorder

Immediate release, Extended-release Oral: Initial: 25 mg once daily (immediate release only) to 50 mg once daily; may gradually increase dose based on response and tolerability every ≥7 days to a usual dosage range of 50 to 200 mg/day in 1 to 3 divided doses based on chosen formulation; maximum recommended dose: 300 mg/day. For the ER tablet, increasing the dose to 100 or 150 mg on day 3 or 4 of therapy may be appropriate for patients with severe symptoms.

• Major depressive disorder

Immediate release, Extended release: Oral: Initial: 50 mg/day on days 1 and 2; increase on day 3 to 150 mg/day in 1 to 3 divided doses based on chosen formulation. Usual dosage range: 150 to 300 mg/day in 1 to 3 divided doses based on selected formulation; however, doses up to 600 mg/day in psychotic depression may be needed and tolerated.

Immediate release, Extended release: Oral: Initial: 50 mg once daily; may gradually increase up to 300 mg/day in 1 to 3 divided doses based on chosen formulation based on response and tolerability.

• Obsessive-compulsive disorder, treatment-resistant

Immediate release: Oral: Initial: 25 to 50 mg once daily; increase dose gradually based on response and tolerability in increments of 25 to 100 mg every 2 to 3 weeks up to 400 mg/day in 1 to 3 divided doses.

• Posttraumatic stress disorder

Immediate release: Oral: Initial: 25 mg once daily at bedtime; increase dose in 25 mg increments every 1 to 2 days up to 100 mg at bedtime by the end of week 1; may further adjust dose based on response and tolerability in increments of 25 mg/day, up to 100 mg/week. Average dose in clinical trials: 100 to 336 mg/day (range: 25 to 800 mg/day in 1 to 3 divided doses). Some experts suggest gradually increasing dose based on response and tolerability in increments of 50 mg/week up to a total daily dose of 400 mg in 1 to 3 divided doses.

• Psychosis in Parkinson disease

Immediate release: Oral: Initial: 12.5 to 25 mg at bedtime; increase dose gradually based on response and tolerability in increments of 12.5 to 25 mg every 1 to 2 weeks; average dose in studies ranged from 40 to 185 mg/day in 1 to 3 divided doses. Some experts gradually increase dose based on response and tolerability up to 100 mg at bedtime and then add a morning dose if needed to control symptoms, up to a maximum of 200 mg/day as tolerated.

• Schizophrenia

Immediate release: Oral: Initial: 25 mg twice daily; increase in increments of 25 to 50 mg/day in 2 or 3 divided doses on days 2 and 3 and increase further to a target dose of 300 to 400 mg/day by day 4. May further adjust dose based on response and tolerability in increments of 50 to 100 mg/day every ≥2 days. Acute therapy usual dosage range: 150 to 750 mg/day in 1 to 3 divided doses. Maintenance therapy usual dosage range: 400 to 800 mg/day in 1 to 3 divided doses; maximum dose: 800 mg/day.

Extended release: Oral: Initial: 300 mg once daily; may increase dose based on response and tolerability in increments of up to 300 mg/day every ≥1 day. Usual dosage range: 400 to 800 mg once daily; maximum dose: 800 mg/day.

Quetiapine is available in the form of an Oral Tablet.

Dosage Adjustment in Kidney Patient

No dosage adjustment is necessary.

Dosage Adjustment in Hepatic Impairment Patient

Oral Tablet: Initial: 25 mg once daily; increase dose based on response and tolerability by 25 to 50 mg/day to an effective dose, dividing total daily dose into 1 to 3 divided doses or 50 mg once daily; increase dose by 50 mg once daily to effective dose, based on individual clinical response and tolerability.

• Cancer (eg, breast cancer)

The clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

• GI motility

Use with caution in patients with decreased GI motility as anticholinergic effects may exacerbate the underlying condition.

• Hepatic impairment

Use with caution in patients with hepatic disease or impairment; dosage adjustment may be required.

• Seizures

Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower the seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.

• Urinary retention (eg, benign prostatic hyperplasia)

Use with caution in patients with urinary retention as anticholinergic effects may exacerbate underlying conditions.

• Common

Dizziness, feeling unsteady, or having trouble keeping your balance, pain in the joints, back, neck, or ears, weakness, dry mouth, vomiting, indigestion, constipation, gas, stomach pain or swelling, increased appetite, excessive weight gain, stuffy nose, headache, pain, irritability, difficulty thinking or concentrating, difficulty speaking or using language, loss of coordination, unusual dreams, numbness, burning, or tingling in the arms or legs, missed menstrual periods, breast enlargement in males, discharge from the breasts, decreased sexual desire or ability.

• Rare

Fainting, falling, seizures, vision changes, uncontrollable movements of your arms, legs, tongue, face, or lips, Priapism, fever, muscle stiffness, pain, or weakness, excess sweating, fast or irregular heartbeat, confusion, unusual bleeding or bruising, sore throat, fever, chills, difficult or painful urination, or other signs of infection, hives, rash, blisters, tightening of the neck muscles or the throat, tongue sticking out, difficulty breathing or swallowing.

• CYP3A4 inhibitors: Coadministration of ketoconazole, a potent inhibitor of cytochrome CYP3A4, resulted in a significant increase in quetiapine exposure. The dose of Quetiapine should be reduced to one-sixth of the original dose if coadministered with a strong CYP3A4 inhibitor.
• CYP3A4 inducers: Coadministration of Quetiapine and phenytoin, a CYP3A4 inducer increased the mean oral clearance of Quetiapine by 5-fold. Increased doses of Quetiapine up to 5-fold may be required to maintain control of symptoms of schizophrenia in patients receiving Quetiapine and phenytoin, or other known potent CYP3A4 inducers. When the CYP3A4 inducer is discontinued, the dose of Quetiapine should be reduced to the original level within 7-14 days.
• Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may reduce the therapeutic effect of Acetylcholinesterase Inhibitors.
• Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson's disease. If an atypical antipsychotic is necessary, consider using clozapine, Quetiapine, or ziprasidone at lower initial doses or a non-dopamine antagonist (e.g., pimavanserin).
• Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin.
• Carbamazepine: Quetiapine may increase serum concentrations of the active metabolite(s) of Carbamazepine. Carbamazepine may decrease the serum concentration of QUEtiapine. Management: Quetiapine dose increases to as much as 5 times the regular dose may be required to maintain therapeutic benefit. Reduce the quetiapine dose to the previous/regular dose within 7 to 14 days of discontinuing carbamazepine.
• Clomipramine: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Clomipramine. QT-prolonging Antipsychotics (Moderate Risk) may enhance the serotonergic effect of Clomipramine. This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk.
• Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
• Fluorouracil Products: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes, when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
• Iohexol: Agents with Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs.
• Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary.
• Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended.
• Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
• Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased.

• Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.

The common side effects of Quetiapine include the following

• Common side effects

Dizziness, Chills, Confusion, Blurred vision, Loss of balance control, Difficulty or painful urination, Constipation, Headache, Acid or sour stomach, Decreased appetite, Sneezing.

• Rare side effects

Dry skin, Irregular menstrual periods, Loss of appetite, Weight gain.

• Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of Quetiapine use in pregnant women. In the limited published literature, there were no major malformations associated with Quetiapine exposure during pregnancy. In animal studies, embryofetal toxicity occurred. Quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

Quetiapine was excreted into human milk. Because of the potential for serious adverse reactions in nursing infants from Quetiapine, a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother’s health.

• Pediatric Use

The safety and effectiveness of Quetiapine in pediatric patients less than 13 years of age with schizophrenia have not been established.

• Geriatric Use

Of the approximately 3700 patients in clinical studies with Quetiapine, 7% (232) were 65 years of age or over. In general, there was no indication of any different tolerability of Quetiapine in the elderly compared to younger adults. Nevertheless, the presence of factors that might decrease pharmacokinetic clearance, increase the pharmacodynamic response to Quetiapine, or cause poorer tolerance or orthostasis, should lead to consideration of a lower starting dose, slower titration, and careful monitoring during the initial dosing period in the elderly. The mean plasma clearance of Quetiapine was reduced by 30% to 50% in elderly patients when compared to younger patients.

Symptoms: Drowsiness, sedation, tachycardia, hypotension, anticholinergic effects, QT prolongation, seizures, status epilepticus, rhabdomyolysis, respiratory depression, urinary retention, confusion, agitation, delirium, and coma.

Management: Supportive treatment. Establish and maintain adequate airways, oxygenation, and ventilation. Monitor and support of the cardiovascular system. For refractory hypotension, administration of IV fluids and/or sympathomimetic agents. Perform gastric lavage within 1 hour of ingestion. For extended-release preparations, diagnostic imaging is recommended for further management.

• Pharmacodynamic

Quetiapine improves the positive and negative symptoms of schizophrenia and major depression by acting on various neurotransmitter receptors, such as the serotonin and dopamine receptors. In bipolar disorder, it improves both depressive and manic symptoms.

• Pharmacokinetics

Absorption

Quetiapine is Rapidly and well absorbed. Its Bioavailability is about 100%. The time taken to reach peak plasma concentration is 1.5 hours for immediate release and 6 hours for extended release.

Distribution

The volume of distribution of Quetiapine is 10±4 L/kg. It is 83% bound to Plasma protein.

Metabolism and Excretion

It is Metabolized in the liver by CYP3A4 to form active N-desalkyl Quetiapine metabolite and 2 inactive metabolites (major sulfoxide metabolite and parent acid metabolite). It is primarily excreted via urine 73% as metabolites, <1% as unchanged drug), via faeces.