Each film coated tablet contains: Olanzapine USP 10 mg.
Pharmacology: Mechanism of Action: The exact mechanism by which Olanzapine exerts its antipsychotic effect is unknown. However, this effect may be mediated through a combination of dopamine and serotonin 5-HT2 antagonism. Olanzapine is a selective monoaminergic antagonist with a strong affinity for serotonin 5-HT2A and 5-HT2C receptors and dopamine D1, D2, D3, D4 receptors.
Olanzapine binds weakly to gamma-aminobutyric acid type A (GABAA), benzodiazepine (BZD, and beta-adrenergic receptors.
Olanzapine's high affinity binding to, and antagonism of, muscarinic M1, M2, M3, M4, and M5 receptors may explain its anticholinergic effects. Olanzapine also binds with high affinity to histamine H1 and alpha1-adrenergic receptors. Antagonism of histamine H1 and alpha1-adrenergic receptors may be responsible for the occurrence of somnolence and orthostatic hypotension, respectively, seen with Olanzapine use.
Pharmacokinetics: Absorption: Well absorbed; however, 40% of the absorbed drug is metabolized before reaching systemic circulation. The rate and extent of Olanzapine absorption are unaffected by food. Oral bioavailability of Olanzapine was not affected by single doses of Cimetidine (800 mg) or Aluminum and Magnesium containing antacids.
Distribution: Extensively distributed throughout the body, with a volume distribution of approximately 1000 L.
Protein binding: High (93%); primarily to albumin and alpha1-acid glycoprotein.
Olanzapine is metabolized primarily through oxidation mediated by cytochrome P450 (CYP) enzymes and by direct glucuronidation. In vitro studies suggest that oxidation is mediated by cytochrome P450 isozymes 1A2 (CYP1 A2) and IID6 (CYP2D6), and by the flavin-containing monooxygenase system. However, studies in subjects who are deficient in CYP2D6 indicate that CYP2D6-mediated metabolism is a minor pathway of Olanzapine metabolism.
Half-life: Elimination: Mean, 30 hours; range, 21 to 54 hours. Mean apparent plasma clearance is 25 L per hour (L/hr); range, 12 to 47 L/hr.
Time to peak concentration: Peak plasma concentration of Olanzapine occurs approximately 6 hours following oral administration. Kinetics are linear over the therapeutic dosage range.
Time to steady-state plasma concentration: Steady-state plasma concentration of Olanzapine, which is approximately twice the concentration seen after a single dose, is achieved in about 1 week with once-a-day dosing.
Elimination: Renal: Approximately 57% of an administered dose is renally excreted, 7% as unchanged drug. Pharmacokinetics of Olanzapine were similar in patients with severe renal function impairment and in patients with normal renal function. Pharmacokinetics of the metabolites of Olanzapine were not studied in patients with renal function impairment.
Fecal: Approximately an administered dose.
In dialysis: Olanzapine is not removed by dialysis.
Used for schizophrenia and for the treatment of moderate to severe mania associated with bipolar disorder.
Oral: Usual adult dose: Antipsychotic: Initially 5 to 10 mg once a day, with a target dose of 10 mg once a day within several days. Dosage may then be adjusted as needed and tolerated at increments or decrements of 5 mg a day, at intervals of not less than one week.
Note: The risk of orthostatic hypotension and syncope may be minimized by initiating therapy with 5 mg a day. If hypotension occurs, a more gradual titration to the target may be considered.
While individual factors that decrease Olanzapine clearance do not necessitate dosage reduction, patients exhibiting a combination of these factors, such as an elderly female nonsmoker, should begin therapy with an initial dosage of 5 mg a day. Dosage should be increased in these patients if clinically necessary.
Debilitated patients, patients predisposed to hypotensive reactions, and patients who may be more pharmacodynamically sensitive to Olanzapine should begin therapy with an initial dosage of 5 mg a day. Dosage should be increased cautiously in these patients if clinically necessary.
In clinical trials, dosages above 10 mg a day were not shown to be more efficacious than 10 mg a day.
Usual adult prescribing limits: 20 mg a day.
Usual pediatric dose: Antipsychotic: Safety and efficacy in children up to 18 years of age have not been established.
Usual geriatric dose: Antipsychotic: see Usual adult dose.
Usual geriatric prescribing limits: see Usual adult prescribing limits.
Clinical Effects: Acute.
Note: During premarketing trials, 67 cases of acute overdosage with Olanzapine were identified. The highest reported ingestion was 300 mg. The only symptoms reported in this patient were drowsiness and slurred speech. Among overdose patients who were evaluated in hospitals, none showed changes in laboratory analyses or electrocardiograms (ECG), and vital signs were usually within normal limits.
Treatment: Multiple drug involvement should be considered. There is no specific antidote to Olanzapine.
To decrease absorption: Gastric lavage, after intubation if patients is unconscious, and administration of activated charcoal with laxative should be considered. Activated charcoal has been shown to reduce absorption of Olanzapine, and may be use since Olanzapine does not reach peak plasma levels for approximately 6 hours following ingestion. The risk of aspiration with induction of emesis may be increased by possible obtundation, seizures, or dystonic reaction of the head and neck.
Specific treatment: Hypotension and circulatory collapse may be treated with intravenous fluids and/or sympathomimetic agents. Because of Olanzapine-induced alpha blockade, sympathomimetics with beta agonist activity, such as epinephrine and dopamine, may worsen hypotension and should not be used.
Monitoring: Continuous ECG monitoring should be employed to detect possible arrhythmias. Close medical supervision should continue until patients recovers.
Supportive care: Airway should be established and maintained to ensure adequate oxygenation and ventilation. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.
Note: Olanzapine is not remove/by dialysis.
Except under special circumstances, this medication should not be used when the following medical problems exists: Hypersensitivity to Olanzapine.
Risk-benefit should be considered when the following medical problems exist: Alzheimer's dementia (dysphagia associated with Olanzapine use may increase risk of aspiration pneumonia; possible increased risk of seizures because of lowered seizure threshold with Alzheimer's dementia); Breast cancer, or history of (prolactin-dependent breast cancers may be exacerbated); Cardiovascular disease, including: Conduction abnormalities or Heart failure or Myocardial infarction or ischemia, or history of, or; Cerebrovascular disease or; Conditions that would predispose to hypotension, including: Dehydration or Hypovolemia (orthostatic hypotension may exacerbated or may exacerbate preexisting cardiovascular or cerebrovascular conditions), (dehydration may predispose medications to increased core body temperature, and antipsychotic medications may disrupt the body's ability to lower core body temperature, thus increasing the risk of heatstroke).
Drug abuse or dependence, history of (patients should be observed closely for signs of misuse or abuse of Olanzapine, as with any new CNS medication); Glaucoma, narrow angle or; Paralytic ileus, history of or; Prostatic hypertrophy, clinically significant (may be exacerbated due to cholinergic antagonism by Olanzapine).
Hepatic function impairment (in premarketing studies, about 1% of patients discontinued Olanzapine treatment due to increased transaminase levels; transaminase levels should be assessed periodically in patients with significant hepatic disease).
Dementia-related psychosis and/or behavioral disturbances: Olanzapine is not approved for the treatment of dementia-related psychosis and/or behavioral disturbances and is not recommended for use in this particular group of patients because of an increase in mortality and the risk of cerebrovascular accident.
Parkinson's disease: The use of Olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended.
Neuroleptic Malignant Syndrome (NMS): NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. Rare cases reported as NMS have also been received in association with Olanzapine.
Carcinogenicity/Tumorigenicity: In carcinogenicity studies, significant increases in the incidence of mammary gland adenomas and adenocarcinomas occurred in female mice receiving 0.5 times the maximum recommended human daily dose (MRHD) of 20 mg per day of Olanzapine on a mg per square meter of body surface area (mg/m2) basis and in female rats receiving two times the MRHD of Olanzapine on a mg/m2 basis. A toxicity study in rats showed prolactin levels to be elevated up to fourfold at the same doses of Olanzapine that were used in the carcinogenicity studies. The increased incidence of mammary gland neoplasms found in rodents after chronic administration of antipsychotic drugs is considered to be prolactin mediated. Drugs that antagonize dopamine D2 receptors, including Olanzapine, are associated with increased prolactin levels in humans.
Because studies have found approximately one third of human breast cancers to be prolactin-dependent in vitro, this prolactin level elevation may be of importance when considering use of these medications in patients with previously detected breast cancers. However, there has been no association shown between chronic administration of medications that elevate prolactin levels and tumorigenesis in either epidemiological or clinical studies to date. Current evidence is too limited to be conclusive. Two carcinogenicity studies were conducted in which mice received Olanzapine for 78 weeks at doses ranging from 0.06 to 5 times the MRHD on a mg/m2 basis (0.8 to 5 times the MRHD in one study, and 0.06 to 2 times the MRHD in the other study). In one of these studies, a significant increase in the incidence of liver hemangiomas and hemangiosarcomas was seen in female mice dosed at two times the MRHD. In the other study, this increased incidence of liver hemangiomas and hemangiosarcomas was not seen, but early mortality was increased in male mice receiving five times the MRHD.
Mutagenicity: Olanzapine demonstrated no mutagenic potential in the following tests: Ames reverse mutation test, in vivo micronucleus test in mice, the chromosomal aberration test in Chinese hamster ovary cells, unscheduled DNA synthesis test in rat hepatocytes, induction of forward mutation test in mouse lymphoma cells, or in vivo sister chromatid exchange test in bone marrow of Chinese hamsters.
Pediatrics: No information is available on the relationship of age to the effects of Olanzapine in pediatric patients. Safety and efficacy have not been established in patients up to 18 years of age.
Geriatrics: No geriatrics-specific problems that would limit the usefulness of Olanzapine in the elderly were seen in studies that included elderly subjects. However, the mean elimination half-life was found to be about 1.5 limes greater in elderly subjects than in younger subjects in one study.
Fertility: The mating performance, but not the fertility, of male rats was impaired during administration of Olanzapine at doses that were 11 times the maximum recommended human daily dose (MRHD) of 20 mg per day on mg per square meter of body surface area (mg/m2). The impairment of mating performance was reversed with discontinuation of Olanzapine administration. Studies in female rats indicate that Olanzapine may produce a delay in ovulation. When Olanzapine was administered at doses that were 1.5 times the MRHD on a mg/m2 basis, female rats showed a decrease in fertility. At doses that were 2.5 times the MRHD on a mg/m2 basis, female rats showed an increased precoital period, and a reduced mating index.
Pregnancy: Adequate and well-controlled studies in humans have not been done.
Of seven pregnancies that occurred during clinical trials with Olanzapine, two resulted in normal births, one resulted in neonatal death due to a cardiovascular defect, three ended in therapeutic abortions, and one ended in spontaneous abortion.
Olanzapine crosses placenta in rats. No evidence of teratogenicity was seen in rats administered Olanzapine at doses up to nine times the MRHD on a mg/m2 basis, or in rabbits administered Olanzapine at doses up to 30 times the MRHD on a mg/m2 basis. At the maximum doses in these studies, early fetal resorptions and increased numbers of nonviable fetuses were observed in rats, and increased fetal resorptions and decreased fetal weight were observed in rabbits. The maximum dose used in the rabbit study was considered to be maternally toxic. Also, in rats, gestation was prolonged at a dose that was five times the MRHD on a mg/m2 basis. FDA Pregnancy Category C.
Breast-feeding: It is not known whether Olanzapine is distributed into human breast milk. However, Olanzapine is distributed into the milk of rats, and use in nursing mothers is not recommended.
Those indicating need for medical attention: Incidence more frequent: Agitation; Akathisia (restlessness or need to keep moving); Extrapyramidal effects, Parkinsonian (difficulty in speaking or swallowing; stiffness of arms or legs; trembling or shaking of hands and fingers); Personality disorder (nonaggressive objectionable behavior).
Note: Akathisia and extrapyramidal effects are dose-related.
Incidence less frequent: Chest pain; Extrapyramidal effects, Dystonic (inability to move eyes; muscle spasms of face, neck, and back; twitching movements); Fever; flu-like symptoms; Mood or Mental changes, including amnesia; Anxiety; Euphoria; Hostility; and Nervousness; Peripheral edema (swelling of feet or ankles); Tardive dyskinesia (lip smacking or puckering; Puffing of cheeks; Rapid or Worm-like movements of tongue; Uncontrolled chewing movements; uncontrolled movements of arms and legs).
Note: Tardive dyskinesia occurs more frequently in elderly patients, especially elderly women. The risk of developing the syndrome, and of experiencing irreversible effects, appears to increase with treatment duration and total cumulative dose, although it may develop at any time during antipsychotic therapy. There is no known treatment for tardive dyskinesia, although partial or complete remission may occur when the antipsychotic medication is withdrawn. Alternatively. the antipsychotic medication may suppress the of the syndrome, masking the underlying process. For these reasons, Olanzapine should be used only in those patients with chronic illness that is responsive to antipsychotic medication, and for whom potentially less harmful treatments are unavailable or inappropriate. Also, the smallest effective dose of Olanzapine should be used and the need for continuing treatment should be assessed periodically.
Incidence rare: Dyspnea (trouble in breathing); Facial edema (swelling face); Menstrual changes: Skin rash; Water intoxication (confusion; mental or physical sluggishness).
Those indicating need for attention continue or bothersome: Incidence more frequent: Amblyopia (problems with vision); Asthenia (weakness); Constipation; Dizziness; Drowsiness; Dry mouth; Headache; Increased weight; Postural hypotension (dizziness or fainting when getting up suddenly from a lying or sitting position); Rhinitis (runny nose); Tremor (trembling or shaking).
Note: Asthenia, drowsiness, dry mouth, and tremor are dose-related. Postural hypotension is most likely to occur during the initial dose-titration period.
During premarketing long-term continuation treatment with Olanzapine (median exposure 238 days), 56% of patients had weight gain >7% of their baseline weight.
The average weight gain was 5.4 kg.
Incidence less frequent: Abdominal pain; Articulation impairment (speaking unclearly); Hypertonia (tightness of muscles); Hypotension (low blood pressure); Increased appetite; Increased cough; Increased salivation (watering mouth); Insomnia (trouble in sleeping); Joint pain; Nausea; Pharyngitis (sore throat); Stuttering; Tachycardia (fast heartbeat); Thirst; Urinary incontinence (trouble in controlling urine); vomiting; weight loss.
Note: Nausea is dose related.
Incidence rare: Decreased libido (decrease in sexual desire); Diplopia (double vision); Palpitation (awareness of heartbeat); Photosensitivity (increased sensitivity of skin to sunlight).
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Alcohol or Central Nervous System (CNS) depression-producing medications, other (additive CNS depressant effects may occur, orthostatic hypotension may be potentiated).
Anticholinergics, other (anticholinergic effects of either these medications or Olanzapine may be increased; disruption of the body's ability to reduce core temperature may be a special consideration).
Hepatotoxic medications (asymptomatic but clinically significant alanine aminotransferase [(ALT (SGPT)] value increases occurred in about 2% of patients in premarketing studies of Olanzapine; about 1% of patients discontinued Olanzapine treatment due to the increased transaminase levels; caution is recommended when Olanzapine is used concurrently with hepatotoxic medications).
Store at temperatures not exceeding 30°C.
N05AH03 - olanzapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics
Olanza 10 FC tab 10 mg
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