Formulary
Olanzapine: Indications, Dosing, Side Effects and Interactions
Olanzapine is a dopamine D 1 , D 2 , D 4 , 5-HT 2 , histamine-1-, and muscarinic-receptor antagonist.
MedNext Academy | 7 min read
Olanzapine: Indications, Dosing, Side Effects and Interactions
Olanzapine is a dopamine D 1 , D 2 , D 4 , 5-HT 2 , histamine-1-, and muscarinic-receptor antagonist.
Drug action
Olanzapine is a dopamine D 1 , D 2 , D 4 , 5-HT 2 , histamine-1-, and muscarinic-receptor antagonist.
Indications and dose
**Schizophrenia,Combination therapy**
- **Adult** (By Mouth): for mania 10 mg daily, adjusted according to response, usual dose 5-20 mg daily, doses greater than 10 mg daily only after reassessment, when one or more factors present that might result in slower metabolism (e.g. females, elderly, non-smoker) consider lower initial dose and more gradual dose increase; maximum 20 mg per day.
**Preventing recurrence in bipolar disorder**
- **Adult** (By Mouth): 10 mg daily, adjusted according to response, usual dose 5-20 mg daily, doses greater than 10 mg daily only after reassessment, when one or more factors present that might result in slower metabolism (e.g. females, elderly, non-smoker) consider lower initial dose and more gradual dose increase; maximum 20 mg per day.
**Monotherapy**
- **Adult** (By Mouth): for mania 15 mg daily, adjusted according to response, usual dose 5-20 mg daily, doses greater than 15 mg daily only after reassessment, when one or more factors present that might result in slower metabolism (e.g. females, elderly, non-smoker) consider lower initial dose and more gradual dose increase; maximum 20 mg per day.
**Control of agitation and disturbed behaviour in schizophrenia or mania**
- **Adult** (By Intramuscular Injection): Initially 5-10 mg for 1 dose; usual dose 10 mg for 1 dose, followed by 5-10 mg after 2 hours if required, maximum 3 injections daily for 3 days; maximum daily combined oral and parenteral dose 20 mg, when one or more factors present that might result in slower metabolism (e.g. females, elderly, non-smoker) consider lower initial dose and more gradual dose increase.
- **Elderly** (By Intramuscular Injection): Initially 2.5-5 mg, followed by 2.5-5 mg after 2 hours if required, maximum 3 injections daily for 3 days; maximum daily combined oral and parenteral dose 20 mg, when one or more factors present that might result in slower metabolism (e.g. females, elderly, non-smoker) consider lower initial dose and more gradual dose increase.
**Schizophrenia, Combination therapy for mania for olanzapine**
- **Child 12-17 years (under expert supervision)** (By mouth): Initially 5-10 mg daily, adjusted according to response, usual dose 5-20 mg daily, doses greater than 10 mg daily only after reassessment, when one or more factors present that might result in slower metabolism (e.g. females, non-smoker) consider lower initial dose and more gradual dose increase; maximum 20 mg per day.
**Monotherapy for mania for olanzapine**
- **Child 12-17 years (under expert supervision)** (By mouth): 15 mg daily, adjusted according to response, usual dose 5-20 mg daily, doses greater than 15 mg daily only after reassessment, when one or more factors present that might result in slower metabolism (e.g. females, non-smoker) consider lower initial dose and more gradual dose increase; maximum 20 mg per day.
Cautions
For all antipsychotic drugs Blood dyscrasias; cardiovascular disease; conditions predisposing to seizures; depression; diabetes (may raise blood glucose); epilepsy; history of jaundice; myasthenia gravis; Parkinson's disease (may be exacerbated); photosensitisation (may occur with higher dosages); prostatic hypertrophy; severe respiratory disease; susceptibility to angle-closure glaucoma Cautions, further information Cardiovascular disease An ECG may be required, particularly if physical examination identifies cardiovascular risk factors, personal history of cardiovascular disease, or if the patient is being admitted as an inpatient. Elderly Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria to aid medication reviews (see Prescribing in the elderly for information). Potentially inappropriate: for all antipsychotics (other than quetiapine and clozapine) in patients with parkinsonism or Lewy Body Disease (risk of severe extrapyramidal symptoms) in behavioural and psychological symptoms of dementia (BPSD), unless symptoms are severe and other non-pharmacological treatments have failed (increased risk of stroke) for use as a hypnotic, unless sleep disorder is due to psychosis or dementia (risk of confusion, hypotension, extrapyramidal side-effects, and falls) in patients prone to falls (may cause gait dyspraxia, parkinsonism) if prescribed a phenothiazine (other than prochlorperazine for nausea, vomiting, or vertigo; chlorpromazine for relief of persistent hiccups; levomepromazine as an antiemetic in palliative care) as first-line treatment (sedative, significant antimuscarinic (anticholinergic) toxicity in older people, and safer and more efficacious alternatives exist) if prescribed an antipsychotic drug with moderate or marked antimuscarinic effects (e.g. chlorpromazine, clozapine, flupenthixol, fluphenazine, pipothiazine, promazine, and zuclopenthixol) in patients with a history of prostatism or urinary retention (high risk of urinary retention) Cautions For olanzapine Bone-marrow depression; hypereosinophilic disorders; low leucocyte count; low neutrophil count; myeloproliferative disease; paralytic ileus Cautions, further information CNS and respiratory depression With intramuscular use: Blood pressure, pulse and respiratory rate should be monitored for at least 4 hours after intramuscular injection, particularly in those also receiving a benzodiazepine or another antipsychotic (leave at least one hour between administration of olanzapine intramuscular injection and parenteral benzodiazepines).
Contraindications
With intramuscular use Acute myocardial infarction; bradycardia; recent heart surgery; severe hypotension; sick sinus syndrome; unstable angina
Side effects
For all antipsychotic drugs Common or very common Agitation; amenorrhoea; arrhythmias; constipation; dizziness; drowsiness; dry mouth; erectile dysfunction; fatigue; galactorrhoea; gynaecomastia; hyperglycaemia; hyperprolactinaemia; hypersalivation; hypotension (dose-related); insomnia; leucopenia; movement disorders; muscle rigidity; neutropenia; parkinsonism; postural hypotension (dose-related); QT interval prolongation; rash; seizure; tremor; urinary retention; vomiting; weight increased Uncommon Agranulocytosis; confusion; neuroleptic malignant syndrome (discontinue-potentially fatal) Rare or very rare Sudden death; withdrawal syndrome neonatal Side-effects, further information For depot antipsychotics-side-effects may persist until the drug has been cleared from its depot site. Overdose Phenothiazines cause less depression of consciousness and respiration than other sedatives. Hypotension, hypothermia, sinus tachycardia, and arrhythmias may complicate poisoning. For details on the management of poisoning see Antipsychotics under Emergency treatment of poisoning . Side-effects For olanzapine General side-effects: Common or very common Anticholinergic syndrome; appetite increased; arthralgia; asthenia; eosinophilia; fever; glycosuria; oedema; sexual dysfunction Uncommon Abdominal distension; alopecia; breast enlargement; diabetes mellitus; embolism and thrombosis; epistaxis; memory loss; oculogyration; photosensitivity reaction; urinary disorders Rare or very rare Hepatic disorders; hypothermia; pancreatitis; rhabdomyolysis; thrombocytopenia Specific side-effects: Common or very common With oral use Hypersomnia Uncommon With intramuscular use Respiratory disorders; speech impairment With oral use Diabetic coma; dysarthria; ketoacidosis Rare or very rare With intramuscular use Withdrawal syndrome Frequency not known With intramuscular use Cerebrovascular adverse events; drug reaction with eosinophilia and systemic symptoms (DRESS); erythema; fall; gait abnormal; hallucinations; pneumonia
Interactions
**Severe interactions:**
- Inhibition of CYP1A2 Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of olanzapine.
- Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.
**Other interactions (17):**
- Potential interactions affecting olanzapine Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine.
- Induction of CYP1A2 The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to reduced olanzapine concentrations.
- Only slight to moderate increase in olanzapine clearance has been observed.
- The clinical consequences are likely to be limited, but clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary (see section 4.2).
- The mean increase in olanzapine Cmax following fluvoxamine was 54 % in female non-smokers and 77 % in male smokers.
- The mean increase in olanzapine AUC was 52 % and 108 % respectively.
Pregnancy
For all antipsychotic drugs Extrapyramidal effects and withdrawal syndrome have been reported occasionally in the neonate when antipsychotic drugs are taken during the third trimester of pregnancy. Following maternal use of antipsychotic drugs in the third trimester, neonates should be monitored for symptoms including agitation, hypertonia, hypotonia, tremor, drowsiness, feeding problems, and respiratory distress. Pregnancy For olanzapine Use only if potential benefit outweighs risk; neonatal lethargy, tremor, and hypertonia reported when used in third trimester.
Breast feeding
For all antipsychotic drugs There is limited information available on the short- and long-term effects of antipsychotic drugs on the breast-fed infant. Animal studies indicate possible adverse effects of antipsychotic medicines on the developing nervous system. Chronic treatment with antipsychotic drugs whilst breast-feeding should be avoided unless absolutely necessary. Phenothiazine derivatives are sometimes used in breast-feeding women for short-term treatment of nausea and vomiting. Breast feeding For olanzapine Avoid-present in milk.
Hepatic impairment
Manufacturer advises caution. Dose adjustments Consider initial dose of 5 mg and cautious titration. M
Renal impairment
Dose adjustments Consider initial dose of 5 mg. M
Medicinal forms
Solution,Tablet,Tablet,Solution
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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