Introduction Olanzapine an atypical antipsychotic approved for the treatment of schizophrenia and bipolar disorder. Olanzapine is structurally similar to clozapine, but is classified as a thienobenzodiazepine. It is a Serotonin dopamine antagonists (SDAs) and also known as second-generation or atypical antipsychotic drugs. These drugs include risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), clozapine (Clozaril), and ziprasidone (Geodon).
ACTION structurally and pharmacologically similar to the atypical antipsychotic clozapine. mechanism of action is not completely understood. Antipsychotic effects may be related to blockade of dopamine (D1, D2, D3, D4), serotonin (5HT2, 5HT3, 5HT6), histamine (H1), alpha-1 adrenergic and muscarinic (M1-M5, particularly M1) receptors. Typical antipsychotics strongly block dopamine receptors. In contrast, olanzapine blocks serotonin receptors (5HT2) more strongly than dopamine (D2) receptors. Blockade of 5HT2 receptors is mechanism for effects on negative symptoms in schizophrenia. Muscarinic blocking (anticholinergic) effects and lower affinity for dopamine receptors may possibly account for the decreased incidence of extrapyramidal symptoms (EPS) seen with olanzapine. Effect on prolactin levels is minimal.
PHARMACOKINETICS: Well absorbed after oral administration; absorption is not changed by food. Peak plasma levels occur 5-8 hours after an oral dose. Plasma levels appear to have a correlation with therapeutic effect, requiring about 23 ng/mL for an antischizophrenic effect. Onset of antipsychotic effects is seen 1-2 weeks of treatment. Half-life ranges from 21-54 hours (mean 30 hours). Highly protein bound (about 93%) with a volume of distribution of 10-18 L/kg. Metabolized in the liver to inactive metabolites mainly by Cytochrome P450, isozyme CYP1A2, Flavin-containing Monooxygenase (FMO) 3, and N-glucuronidation.
Conti.. Minor pathways involve CYP2D6 and possibly CYPS2C19 isozymes. About 40% is metabolized in the first pass through the liver. Because of the number of possible routes of metabolism, inhibition of cytochrome oxidase pathways does not markedly affect elimination of olanzapine. About 57% of a dose is excreted in urine principally as metabolites (only 7% as unchanged drug) and about 30% in the feces. In single dose studies, half-life was not affected by decreased renal function or clinically significant cirrhosis (in smokers). In general, olanzapine elimination is slower in women, the elderly and non-smokers. In a small single dose study, mean half-life in elderly women was 55 hours, compared to a mean of 49 hours in elderly men. Olanzapine is not removed by dialysis.
USES Approved for the treatment of acute mania, also are useful as adjunctive therapy in treatment-resistant depression posttraumatic stress disorder (PTSD)and behavioral disturbances associated with dementia. Bipolar Disorder- Olanzapine is effective as monotherapy for the treatment of mania and mixed states its also effective for the same conditions when combined with lithium or valproate. olanzapine is effective for both psychotic and no psychotic patients. IM use olanzapine indicated for agitation that can be associated with schizophrenia or mania. Its augment antidepressants in the acute management of major depression. Olanzapine is potentially use in treatment-refractory patients because it has a biochemical profile similar to that of clozapine and is more effective at treating negative symptoms than haloperidol.
OTHER USES Olanzapine has been found to be effective in autism and in producing weight gain in patients with anorexia nervosa. Outwardly aggressive or violent behavior some times seen in Acquired immunodeficiency syndrome (AIDS), Tourettes disorder, Huntingtons disease, and Lesch-Nyhan syndrome. Risperidone n olanzapine is used to control aggression and self-injury in children. Pregnancy- no increased risk of malformation or neonatal complications, except for lower birth weight in the exposed group. neonates exposed to olanzapine showed trends toward lower birth weights and more neonatal intensive care unit admissions than neonates exposed to other antipsychotic medication.
Conti.. Oleanzapine have also been co administered with sympathomimetics, such as methylphenidate or dextroamphetamine, to children with attention- deficit/hyperactivity disorder (ADHD) who are comorbid for either opposition-defiant disorder or conduct disorder. Olanzapine also useful in persons who have severe tardive dyskinesia. Also its use to suppresses the abnormal movements of tardive dyskinesia, but does not appear to worsen the movement disorder. Its effective for treating psychotic depression and for psychosis secondary to head trauma, dementia, or treatment drugs.
ADVERSE EFFECTS Increased Mortality in Dementia Patients - Olanzapine has been associated with increased mortality in patients treated for psychosis associated with dementia. increased risk of cerebrovascular events in dementia patients including stroke and transient ischemic attacks. Weight Gain - patients gained approximately 2 lb per week. Hyperlipidemia - Patients treated with olanzapine may experience serious increases in total cholesterol, LDL cholesterol, and triglycerides.
ADVERSE EFFECTS Hyperglycemia, Insulin Resistance, Diabetes Mellitus - More impaired in olanzapine as compared to other antipsychotic, elevations in blood glucose that are life-threatening some times. Also olanzapine is associated with an increase in insulin resistance in both obese and non obese patients. olanzapine treatment is associated with an increased risk for the development of type 2 diabetes mellitus. Somnolence, dry mouth, dizziness, constipation, dyspepsia, increased appetite, akathisia, and tremor are associated with olanzapine use. There is transaminase elevation, but no jaundice. A dose-related risk exists of extrapyramidal side effects.
RECOMMENDED TESTS Regular assessment of blood sugar. Close monitoring in LDL, TGS, level in obese and in pt with k/c/o DM, HTN. Pt.
Dosage and Administration Olanzapine is available as 2.5-, 5-, 7.5-, 10-, 15-, and 20-mg tablets; as 5-, 10-, 15-, and 20-mg orally disintegrating tablets and vials with 10 mg of olanzapine. Treatment of Schizophrenia- Its effective at dosages between 7.5 and 20.0 mg per day administered once daily without regard to meals. A 5 to 10 mg is well tolerated in most adult patients recommended initial dose is then adjusted as necessary within the range of 5 to 20 mg per day. Maintenance in Schizophrenia-doses of 10 to 20 mg daily of olanzapine are sufficient to prevent psychotic relapse in stabilized patients.
Continue.. Treatment of Bipolar Disorder - Patients with mania or mixed states can usually be started on 10 to 15 mg daily of oral olanzapine. Doses can be increased to 20 or 25 mg daily. Similar doses can be prescribed when olanzapine is added to lithium or valproate. Patients with bipolar disorder who have been stabilized can usually be maintained on 5 to 10 mg of olanzapine daily. Special Populations - Patients who are debilitated or vulnerable to hypotension should be started on 5 mg or less. Doses of 5 to 10 mg orally may effective for schizophrenia or bipolar disorder in these individuals. IM Olanzapine in Agitation Associated with Schizophrenia or Bipolar Disorder - IM doses of 2.5 to 10 mg have been effective in reducing agitation. In most cases, 10 mg IM is an appropriate initial dose.
Drug Interactions Fluvoxamine and cimetidin increase, whereas carbamazepine and phenytoin decrease serum concentrations of olanzapine. Ethanol increases olanzapine absorption by more than 25 percent, leading to increased sedation. Olanzapine has little effect on the metabolism of other drugs.