Olanzapine

Indications

Olanzapine is used for: Schizophrenia, Bipolar disorder, Agitation, Mania

Adult Dose

Oral Schizophrenia Adult: 5-10 mg/day initially; if necessary, may be titrated upward in increments of 5 mg/day at intervals >1 week Maintenance: 10-20 mg/day; not to exceed 20 mg/day Bipolar Mania Used as monotherapy or in combination with lithium or valproate Monotherapy: 10-15 mg/day PO initially Adjunct to lithium or valproate: 10 mg/day PO initially Maintenance: 5-20 mg/day PO; not to exceed 20 mg/day Depression in bipolar disorder Use in combination with fluoxetine 5 mg in evening; adjusted to range of 5-12.5 mg/day; may be increased up to 20 mg/day in resistant depression Hepatic impairment: Initial: 5 mg daily.

Child Dose

Oral Bipolar I Disorder (Manic or Mixed Episodes) <13 years: Safety and efficacy not established 13-17 years: 2.5-5 mg/day PO initially; target dosage, 10 mg/day; adjust by increments/decrements of 2.5-5 mg; dosage range, 2.5-20 mg/day Schizophrenia <13 years: Safety and efficacy not established 13-17 years: 2.5-5 mg/day PO initially; target dosage, 10 mg/day; adjust by increments/decrements of 2.5-5 mg; dosage range, 2.5-20 mg/day

Renal Dose

Renal impairment: Initial: 5 mg daily.

Administration

May be taken with or without food.

Contra Indications

Angle-closure glaucoma; lactation. IM: History of CVS disease, heart surgery.

Precautions

Patient w/ cerebrovascular disease or conditions predisposing to hypotension, benign prostatic hyperplasia, paralytic ileus, DM, Parkinson's disease, history of blood dyscrasias, bone marrow depression, hypereosinophilic disorders, myeloproliferative disease, history of seizures or conditions that lower the seizure threshold. IM: Acute MI, unstable angina, severe hypotension or bradycardia, sick sinus syndrome, recent heart surgery. Elderly w/ dementia-related psychosis. Hepatic and renal impairment. Pregnancy and lactation. Patient Counselling This drug may cause somnolence and dizziness, if affected, avoid driving and operating machinery. Avoid cigarette smoking. Monitoring Parameters Monitor BP, pulse and resp rate for at least 4 hr after IM inj. Clinical monitoring for hyperglycaemia, plasma lipids and wt. Lactation: Drug enters breast milk; not recommended

Pregnancy-Lactation

Interactions

Olanzapine may antagonise the effects of levodopa and dopamine agonists. Drugs that induce CYP1A2 or glucuronyl transferase enzymes e.g. omeprazole and rifampicin, may increase olanzapine clearance. Inhibitors of CYP1A2 may potentially inhibit olanzapine elimination. Carbamazepine may increase the clearance of olanzapine. Concomitant admin of activated charcoal reduced the oral bioavailability of olanzapine by 50-60%. Caution should be taken when olanzapine is administered with centrally acting drugs and alcohol.

Adverse Effects

Side effects of Olanzapine : >10% Orthostatic hypotension (>20%), Weight gain, dose dependent (5-40%), Hypertriglyceridemia (<39%), Hypercholesterolemia (<39%), Somnolence, dose dependent (6-39%), Extrapyramidal symptoms (EPS), dose dependent (15-32%), Xerostomia (9-22%), Weakness (2-20%), Dizziness (4-18%), Accidental injury (12%), Insomnia (12%), Elevated alanine aminotransferase (ALT) level (5-12%), Constipation (9-11%), Dyspepsia (7-11%), Hyperprolactinemia (30%), Hyperglycemia (12.8%) 1-10% Hypotension (2%), Postural hypotension (1%), Tremor (1%), Asthenia (2%), Akathisia reactions (2%), Parkinsonism reactions (4%) <1% Syncope, Sudden cardiac death, Hyperglycemia, Diabetic coma with ketoacidosis, Diabetic ketoacidosis, Acute hemorrhagic pancreatitis, Venous thromboembolism, Immune hypersensitivity reaction, Cerebrovascular disease, Seizure, status epilepticus, Suicidal intent, Pulmonary embolism, Death, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia Potentially Fatal: Exacerbation of preexisting diabetes sometimes leading to ketoacidosis. Neuroleptic malignant syndrome.

Mechanism of Action

Olanzapine is an atypical antipsychotic with affinity for serotonin 5-HT2A/2C, dopamine, muscarinic M1-M5, histamine H1 and adrenergic alpha1 receptors.