Adult: As immediate-release/film-coated tab: Initially, 25 mg bid on day 1, followed by 50 mg bid on day 2, 100 mg bid on day 3 and 150 mg bid on day 4. Titrate dose according to response between 300-450 mg daily given in 2 divided doses from day 4 onwards. Max: 750 mg daily. As extended-release tab: 300 mg once daily on day 1, followed by 600 mg once daily on day 2. Adjust according to patient response between 400-800 mg daily. Usual dose: 600 mg once daily. Max: 800 mg daily. Elderly: As immediate-release/film-coated tab: Slower rate of dose titration and lower daily therapeutic dose. As modified-release tab: Initially, 50 mg once daily, adjusted in increments of 50 mg according to response.
Oral Acute manic episodes of bipolar disorder
Adult: As immediate-release/film-coated tab: 50 mg bid for day 1, followed by 100 mg bid for day 2 then 150 mg bid on day 3 and 200 mg bid on day 4. Adjust in increments up to 200 mg daily according to response. Usual dose: 400-800 mg daily in 2 divided doses. Max: 800 mg daily. As extended-release tab: 300 mg once daily on day 1, followed by 600 mg daily on day 2 adjusted according to response. Usual dose: 400-800 mg once daily. Elderly: As immediate-release/film-coated tab: Slower rate of dose titration and lower daily therapeutic dose. As extended-release tab: Initially, 50 mg once daily, adjusted in increments of 50 mg according to response.
Oral Depressive phase of bipolar disorder
Adult: As immediate-release/film-coated/extended-release tab: 50 mg once daily on day 1 to be taken at bedtime, followed by 100 mg once daily on day 2 then 200 mg once daily on day 3 and 300 mg once daily on day 4. Adjust according to patient response. Usual dose: 300 mg once daily. Max: 600 mg daily. Elderly: As immediate-release tab/film-coated: Slower rate of dose titration and lower daily therapeutic dose.
Oral Prophylaxis of bipolar disorder
Adult: As immediate-release tab/film-coated: Continue at the dose effective for treatment of bipolar disorder and adjust to lowest effective dose. Usual dose: 300-800 mg daily in 2 divided doses. As extended-release tab: Continue at the dose effective for treatment of bipolar disorder and adjust to lowest effective dose. Usual dose: 300-800 mg once daily.
Oral Major depressive disorder
Adult: In combination with other drugs for major depression: As extended-release tab: 50 mg once daily for days 1 and 2, dose to be taken at bedtime, followed by 150 mg once daily for days 3 and 4 then adjusted according to response. Usual dose: 150-300 mg once daily. Elderly: As extended-release tab: Initially, 50 mg once daily on days 1-3 then increased to 100 mg once daily on day 4 and 150 mg on day 8. Adjust in increments of 50 mg according to response, the lowest effective dose should be used. Usual dose: 50-300 mg once daily. 300 mg dose should not be reached prior to day 22 of treatment.
Hepatic Impairment
Schizophrenia; Acute manic episodes of bipolar; Depressive phase of bipolar disorder; Prophylaxis of bipolar disorder:
As immediate-release/film-coated tab: Initially, 25 mg daily, increased in increments of 25-50 mg daily according to patient response.
Administration
film-coated tab: May be taken with or without food. extended-release: Should be taken on an empty stomach. Take w/o food or w/ a light meal. Swallow whole, do not chew/crush.
Contraindications
Concomitant use with CYP3A4 inhibitors (e.g. HIV protease inhibitor, azole-antifungal agents, erythromycin, clarithromycin, nefazodone).
Special Precautions
Patient at risk of seizures (e.g. head trauma, brain damage), with Lewy body dementia, Parkinson disease dementia, cardiovascular disease or cerebrovascular disease, conditions predisposing to hypotension; at risk of QT prolongation (e.g. heart failure, cardiac myopathy), urinary retention, BPH, increased intraocular pressure, Alzheimer’s disease, diabetes, hyperlipidaemia, breast cancer or other prolactin-dependent tumours. History of alcohol or drug abuse. Behavioural changes and increased risk of suicidal thinking. Avoid abrupt withdrawal. Not intended for treatment in elderly patients with dementia-related psychosis. Renal and hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Anticholinergic effects (e.g. confusion, agitation, constipation, xerostomia, blurred vision, urinary retention), blood dyscrasias (e.g. leucopenia), oesophageal dysmotility and aspiration, extrapyramidal symptoms (e.g. pseudoparkinsominsm, acute dystonic reactions, akathisia, tardive dyskinesia), withdrawal symptoms, orthostatic hypertension, hyperlipidemia, hyperprolactinemia, anaphylactic reactions, hypothyroidism, weight gain, cataracts, impaired body temperature regulation, pancreatitis, venous thromboembolism (VTE), constipation, cardiomyopathy, myocarditis, dysphagia, constipation, intestinal obstruction. Blood and lymphatic system disorders: Decreased haemoglobin. Cardiac disorders: Tachycardia, palpitation. Endocrine disorders: Decrease T3 and T4, increase TSH. Eye disorders: Blurred vision. Gastrointestinal disorders: Dry mouth, constipation, dyspepsia, vomiting. General disorders and administration site conditions: Mild asthenia, irritability, pyrexia. Hepatobiliary disorders: Increased serum transaminases. Metabolism and nutrition disorders: Serum triglyceride elevations, total cholesterol elevation, HDL decrease, increase appetite, peripheral oedema. Nervous system disorders: Dizziness, somnolence, headache. Psychiatric disorders: Abnormal dreams and nightmares. Respiratory, thoracic and mediastinal disorders: Dyspnoea, rhinitis, nasal congestion. Potentially Fatal: Suicidal ideation and behaviour, neuroleptic malignant syndrome (e.g. hyperpyrexia, muscle rigidity, altered mental status, autonomic instability), hyperglycaemia and/or development or exacerbation associated with ketoacidosis or coma, severe neutropenia, agranulocytosis, QT prolongation.
Monitor worsening and emergence of suicidal thoughts and behaviours. Monitor blood pressure, weight, height, BMI, waist circumference, CBC, electrolytes, LFT, TSH, free T4, thyroid assessment, fasting glucose level, fasting lipid panel. Assess for changes in menstruation, libido, erectile and ejaculatory function, abnormal involuntary movements or parkinsonian signs, tardive dyskinesia. Monitor for symptoms of hyperprolactinaemia (e.g. breast enlargement, galactorrhoea). Observe for visual changes and perform ocular and lens examinations prior to treatment and at 6-month intervals. Complete fall risk assessment prior to therapy and periodically during treatment. Monitor for symptoms of hyperglycaemia (e.g. polydipsia, polyuria, polyphagia, weakness).
Overdosage
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 airway, 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.
Drug Interactions
Increased serum concentration with CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, nefazodone). Decreased serum concentration with CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampin). Extended-release preparations may antagonise actions of dopaminergics (e.g. levodopa). Increased risk of QT prolongation with class IA antiarrhythmics (e.g. quinidine, procainamide), class III antiarrhythmics (e.g. amiodarone, sotalol), antipsychotic medications (e.g. ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g. gatifloxacin, moxifloxacin), pentamidine, levomethadyl acetate, methadone).
Food Interaction
Increased bioavailability with high-fat meals. Enhanced CNS depressant effect of alcohol. Decreased plasma concentration of quetiapine with St. John’s wort.
Lab Interference
May cause false-positive result in urine screening for TCAs and methadone.
Action
Description: Mechanism of Action: Quetiapine is a dibenzothiazepine atypical antipsychotic agent. Its clinical antipsychotic properties and low extrapyramidal side effect are 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. Pharmacokinetics: Absorption: Rapidly and well absorbed. Bioavailability: 100%. Increased bioavailability with high-fat meals. Time to peak plasma concentration: 1.5 hours (immediate release); 6 hours (extended-release). Distribution: Volume of distribution: 10±4 L/kg. Plasma protein binding: 83%. Metabolism: Metabolised in the liver by CYP3A4 to form active N-desalkyl quetiapine metabolite and 2 inactive metabolites (major sulfoxide metabolite and parent acid metabolite). Excretion: Via urine (73% as metabolites, <1% as unchanged drug), via faeces (20%). Elimination half-life: Approx 7 hours (extended-release).
Chemical Structure
Quetiapine Source: National Center for Biotechnology Information. PubChem Database. Quetiapine, CID=5002, https://pubchem.ncbi.nlm.nih.gov/compound/Quetiapine (accessed on Jan. 22, 2020)
N05AH04 - quetiapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics.
References
Anon. Quetiapine Fumarate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 09/12/2014.Anon. Quetiapine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/11/2019.Buckingham R (ed). Quetiapine Fumarate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/11/2019.Joint Formulary Committee. Quetiapine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/11/2019.Quetiapine Extended-Release Tablet, Film Coated (Amneal Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/11/2019.Quetiapine Fumarate Tablet (West-Ward Pharmaceuticals Corp). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/11/2019.Seroquel (AstraZeneca UK Limited). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 12/12/2019.
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