1. Olanzapine
Drug and discussion

2. 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).

3. 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.

4. 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.

5. 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.

6. 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.

7. 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), Tourette's
disorder, Huntington's 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.