Quetiapine
Class: antipsychotic – atypical, second generation
Indications (NB some may be unlicensed): acute and chronic psychoses including schizophrenia, manic episodes associated with bipolar disorder, nausea and vomiting, delirium
Contraindications/cautions: liver dysfunction, cardiovascular and cerebrovascular disease, hypotension, seizures, Parkinsons, DLB; caution with other drugs causing QT prolongation eg domperidone
Adverse reactions: common: drowsiness, dry mouth, GI effects (constipation), tachycardia, dizziness, headache, agitation, insomnia, weight gain, dyspepsia; less common: neuroleptic malignant syndrome, tardive dyskinesia, cholesterol changes, thyroid hormone changes, peripheral oedema, diabetes, extrapyramidal adverse effects, hepatotoxicity, blood disorders, postural hypotension, seizures, dyspnoea, sweating, rash
Metabolism/clearance: metabolised almost completely mainly in the liver by the metabolising enzyme CYP3A. Elimination renal (75%) and faecal (25%) – caution in renal impairment
Interactions:
- increased clinical effect/toxicity of quetiapine (due to increased blood concentrations) may occur with some CYP metabolising enzyme inhibitors (see above) e.g. aprepitant, clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nelfinavir, ritonavir, telapravir, voriconazole
- decreased clinical effect/toxicity of quetiapine (due to decreased blood concentrations) may occur with some CYP metabolising enzyme inducers (see above) e.g. carbamazepine, phenobarbitone, phenytoin, rifampicin, St John’s wort
- possible increase risk of extrapyramidal effects with dopamine antagonists e.g. metoclopramide
- additive hypotension with antihypertensives e.g. propranolol may occur
- additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), opioids, alcohol
| Dosing: | ||
|---|---|---|
| oral: | anxiety, depression, psychosis | start with 12.5 to 25 mg bd – increase in 12.5 to 25 mg increments over 3 to 4 days. Typical effective dose – anxiety 50 to 150 mg/24 hours; depression – 150 to 300 mg/24 hours; psychosis 300 to 450 mg/24 hours |
| mania | initially 50 mg bd increasing daily to 200 to 800 mg per day in 2 divided doses; increase in 50 mg dose increments | |
| delirium | start with 12.5 mg bd; increase in 12.5 to 25 mg increments – mean effective dose 75 mg/24 hours (range 25 to 300 mg/ 24 hours) (PCF8) | |
| subcut: | not available | |
| rectal: | not available | |
Syringe driver: not available
Mechanism of action: antagonises serotonin, dopamine, 5-HT, alpha-adrenoreceptor and histamine-1 receptors in the CNS
Bioavailability > 75%
Onset of action: delirium: hours to days psychoses: 1 to 2 weeks
Time to peak plasma conc: 1.5 hours
Duration of action: 12 hours (PCF8)
Notes:
- 12.5 mg dose = halve a 25 mg tablet. Some references recommend commencing on 25 mg dose – lower does in elderly, renal or hepatic impairment
- lower potential for neurological adverse effects (e.g. extrapyramidal effects) than conventional antipsychotics
- can be used in acute delirium and behavioural disturbances associated with brain tumours