OLANZAPINE

OLANZAPINE

  • Brand: OLANZAPINE-TEDAPHARM
  • Generic name:OLANZAPINE
  • Pharmaceutical form:Tab
  • Amount: 100
  • Pharmaceutical group: CENTRAL NERVOUS SYSTEM DRUGS
Download brochure OLANZAPINE
OLANZAPINE

Olanzapine
Olazin®
 
Category:
Antipsychotic  
 (USP DI) 
 
Chemistry:                  
2-methyl-4-(4-methyl-l-piperazinyl)-10H-thieno[2,3-b] [1,5]benzodiazepine.   
C17H20N4S = 312.4          
 
Mechanism of action / Pharmacokinetics:
Olanzapine is a thioenobenzodiazepine atypical antipsychotic. The mechanism of action of olanzapine, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug’s efficacy in schizophrenia is mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism. The mechanism of action of olanzapine in the treatment of acute manic or mixed episodes associated with Bipolar I Disorder is unknown. Olanzapine’s antagonism of muscarinic M1-5 receptors may explain its anticholinergic-like effects. Olanzapine’s antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Olanzapine’s antagonism of adrenergic  1 receptors may explain the orthostatic hypotension observed with this drug.
(PDR, Martindale) 
Pharmacokinetics properties:
Absorption Well absorbed; 40% of the absorbed drug is metabolized before reaching systemic circulation; the rate & extent of olanzapine absorption are unaffected by food.
Peak plasma concentration Achieved about 5 to 8 hours after oral doses
Distribution Extensively distributed throughout  the body with the volume of distribution of approximately 1000 L
Biotransformation 
Extensively metabolized in the liver, primarily by direct glucuronidation and by oxidation mediated through the CYP450 isoenzymes CYP1A2 and to a lesser extent CYP2D6. The 2 major metabolites 10-N-glucuronide and 4-N-desmethyl olanzapine appear to be inactive.
Half - life Elimination: mean 30 hours
Protein binding High 93%
Time to peak concentration Approximately  6 hours following oral administration
Time to steady - state plasma concentration Which is approximately  twice the concentration seen after a single dose, is achieved in about 1 week once-a-day dosing 
Elimination Renal: approximately 57% of an administered dose is renally excreted, 7% as unchanged drug.
Fecal: approximately 30% of an administered dose.
Dialysis Is not removed by dialysis
 
 (USPDI, Martindale) 
 
Indications:
Management of schizophrenia; Treatment of moderate to severe mania associated with bipolar disorder; Rapid control of agitation and disturbed behavior; Acute manic and /or mixed episodes associated with bipolar disorder.   
 (Facts, Martindale)
 
Contraindications:
Olanzapine is contraindicated in patients with a known hypersensitivity to the product. 
 (PDR)
 
Warnings and precautions:
- Olanzapine may induce orthostatic hypotension associated with dizziness, tachycardia, and 
in some patients, syncope, especially during the initial dose titration period.
- Olanzapine should be used with particular caution in patient with known cardiovascular 
disease, cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities) and conditions which would predispose patients to hypotension 
 
(dehydration, hypovolemia, and treatment with antihypertensive medications) where the 
occurrence of syncope, or hypotension and/or bradycardia might put the patient at increased medical risk.
- Caution is necessary in patients who receive treatment with other drugs having effects that can induce hypotension, bradycardia, respiratory or central nervous system depression.
- Olanzapine should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold, e.g. , Alzheimer’s dementia.
- Caution should be exercised in patients with signs and symptoms of hepatic impairment.
- Olanzapine should be used cautiously in patients at risk for aspiration pneumonia, patients with clinically significant prostatic hypertrophy, narrow angle glaucoma, or a history of paralytic ileus. 
- Olanzapine increased mortality in elderly patients with dementia-related psychosis.
- Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, in patients treated with atypical antipsychotics including olanzapine.
- Neuroleptic malignant syndrome (NMS) has been reported in association with administration of olanzapine.
- Tardive dyskinesia-A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs such as Olanzapine.
- Prescriptions for olanzapine should be written for the smallest quantity of tablets consistent 
with good patient management, in order to reduce the risk of overdose and suicide.  
(PDR)  
 
Pregnancy:
Category C.
Olanzapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.  
 (USP DI)
 
Breast – Feeding:
In a study in lactating, healthy women, Olanzapin was excreted in breast milk .Mean infant dose as steady state was estimated to be 1.8% of the maternal Olanzapin dose. It is recommended that women receiving olanzapine should not breast-feed.  
(PDR) 
 
Drug Interactions:
- Co-administration Olanzapine with alcohol and CNS depressants may lead to enhanced CNS 
  depression, especially impairment of motor skills. Dystonic reactions may be precipitated by 
   alcohol. Avoid concurrent use or use with caution.
- Olanzapine may enhance the effects of antihypertensive agents. Olanzapine produce 
 
alpha-adrenergic blockage and may potentiate orthostatic hypotension. Therefor for treatment of antipsychotic induced hypotension, do not use epinephrine, dopamine or other sympathomimetics with beta-agonist activity.
- CYP1A2 inducers (e.g., carbamazepine, omeprazole, rifampin) decrease the olanzapine serum concentrations .May need dosage increase for Olanzapin .Carbamazepin increase Olanzapin clearance 50%.
- Charcoal can decrease the absorption of olanzapine, reducing their effectiveness or toxicity.
- CYP1A2 inhibitors (e.g., fluvoxamine) may increase olanzapine serum concentrations. Dose 
reduction may be needed.
- Coadministration of fluoxetine with olanzapine resulted in a small (16%) increase in Cmax and decrease olanzapine clearance.
- Olanzapine may antagonize the effects of levodopa and dopamine agonists.
- Single dose of olanzapine didn’t affect the pharmacokinetics of imipramine or it's active 
metabolite desipramine, and warfarin.
- Multiple dose of olanzapine didn’t influence the kinetics of diazepam, biperiden, lithium, 
theophylline or its metabolites.
- Single doses of cimetidine (800mg) or aluminum-and magnesium-containing antacids didn’t 
affect the oral bioavailability of olanzapine. 
  (Facts, PDR)
 
Adverse reactions:
Atrial contractions, premature/atrial fibrillation/flutter; bradycardia; cardiac arrest; cerebral vascular accident; CHF; hypertension; hypotension; palpitation; pulmonary embolus; tachycardia; vasodilation; accommodation abnormality; akathisia; akinesia; amnesia; asthenia;ataxia;delirium;dizziness;dreams,abnormal/bizarre/increased/(drowsiness/sedation/somnolence); dysarthia, dyskinesia; dystonia; euphoria; gait abnormal; hypesthesia; hypokinesia; incoordination; insomnia; increased libido; malaise; migraine; neuroleptic malignant syndrome; neuropathy; paresthesia; pseudoparkinsonism; suicide attempt/thought; tardive dyskinesia; tremor; vertigo; acne; alopecia; dermatitis; ecchymosis; eczema; maculopapular skin reactions; pallor; photosensitivity; pruritus; rash, vesiculobullous; seborrhea; urticaria; abdominal distention; appetite increased; constipation; dry mouth; dyspepsia; dysphagia; eructation; esophageal ulcer/esophagitis; fecal impaction; flatulence; gastritis; gastroenteritis; gingivitis; glossitis; incontinence,fecal; intestinal obstruction; melena; mouth ulceration; nausea; paralytic ileus; polydipsia; rectal hemorrhage; salivation; stomatitis; tongue discoloration; tooth caries; vomiting; weight gain; albuminuria; amenorrhea; ejaculation disorders; galactorrhea; glycosuria; gynecomastia; hematuria; impotence; incontinence, urinary; mastalgia; menorrhagia; metrorrhagia; polyuria; priapism; urinary frequancy/urgency increased; urinary retention; vaginal hemorrhage; anemia; hemorrhage; hypercholesterolemia; hyperglycemia; hyperkalemia; hyperlipemia; hypoglycemia; hypokalemia; hyponatremia; hypoproteinemia; leukocytosis; leukopenia; lymphadenopathy; thrombocythemia; thrombocytopenia; hepatitis; allergic reaction; 
 
anaphylactoid reactions; alkaline phosphatase increased; cyanosis; edema of facial, peripheral tongue; arthralgia/joint pain; arthritis; bone pain; bursitis; myopathy; apnea; asthma; increased 
 
cough; dyspnea; epistaxis; hemoptysis; pharyngitis; pneumonia; rhinitis; blepharitis; cataracts; conjunctivitis; diplopia; dry eyes; eye hemorrhage; glaucoma; miosis; mydriasis; tinnitus; accidental injury; back pain; chest pain; chills; cogwheel rigidity; dehydration; diaphoresis; fever; flu syndrome; gout; hypertonia; hypotonia; moniliasis; neck pain/rigidity; pelvic pain; sudden death; thyroiditis; withdrawal syndrome; personality discorder; extremity pain (not joint); amblyopia; articulation impaired; UTI; angiodema; dental pain; intentional injury.  
  (Facts)
 
Over dosage:
CNS depression to the point of somnolence, deep sleeps from which patient can not be aroused, or coma. Hypotension and extrapyramidal symptoms may occur. Other manifestations include: Agitation; restlessness; convulsions; fever; hypothermia; hyperthermia; coma; autonomic reactions; ECG changes; cardiac arrhythmias; tachycardia; hypertension; vomiting; NMS; slurred speech; delirium; respiratory depression or failure; seizures; dry mouth; salivation; ileus; hyperpyrexia; dilated or constricted pupils; cardiac arrest; death. 
(Facts)
 
Dosage and Administration:
The usual adult and geriatric dose for Schizophrenia
The usual initial oral dose is 10mg daily as a single dose, thereafter dosage adjustments may be made according to response at intervals of not less than 24 hours to within the range of 5 to 20 mg daily. That dose above 10 mg daily should be given only after clinical reassessment.
 
- Acute mixed or manic episodes
In bipolar disorder, a recommended initial dose is 10 or 15 mg daily by mouth as monotherapy or 10 mg if given as part of combination therapy. For prevention of recurrence in patients whose manic episodes have responded previously to olanzapine, the recommended starting dose is 10 mg daily.
 
 
- The rapid control of agitation and disturbed behavior
In patients with schizophrenia or mania, olanzapine may be given intramuscularly in an initial 
dose of 5 to 10 mg followed by 5 to 10 mg as required after 2 hours. Not more than 3 injections should be given in any 24-hour period and the maximum daily dose, including olanzapine given by mouth, should not exceed 20 mg. Injections may be given for up to a maximum of 3 days but transfer to oral therapy should be started as soon as possible.
 
 
- Usual adult and geriatric prescribing limits 
   20 mg a day.
 (Martindale) 
- Usual pediatric dose
  Safety and efficacy in children up to 18 years of age have not established  
 (USP DI) 
 
Storage:
Store between 20 and 25C (68 and 77F), unless otherwise specified by manufacturer. Protect from light and moisture. 
(USP DI)
 
How Supplied:
Olanzapine – Tedapharm is available as 2.5, 5 and 15 mg:
1)  2.5 mg tablets are orange, biconvex and film coated. There are blisters of 10 in a box of 100. 
2) 5 mg tablets are white, biconvex and film coated. There are blisters of 10 in a box of 100.
3) 15 mg tablets are deep peach, oval and scored. There are blisters of 10 in a box of 30. 
 
 
References:
1- PDR 2011                       
2-USPDI 2007
3- Martindale (37) 2011      
4- Drug Facts 2011 
 

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