Ozapez

OZAPEZ 5: OZAPEZ 5 is white to off white coloured, round shaped, biconvex, film coated tablets having 'CL 40' debossed on one side and plain on other side.
Each film-coated tablet contains Olanzapine 5 mg.
OZAPEZ 10: OZAPEZ 10 is white to off white coloured, round shaped, biconvex, film coated tablets having 'CL 42' debossed on one side and plain on other side.
Each film-coated tablet contains Olanzapine 10 mg.

Pharmacotherapeutic group: Antipsychotic. ATC Code: N05AH03.
Pharmacology: Pharmacodynamics: Olanzapine is an atypical or second-generation antipsychotic that is a thienobenzodiazepine-derivative antipsychotic agent.
Mechanism of Action: Olanzapine is an antipsychotic which displays potent antagonism of serotonin 5-HT_2A and 5-HT_2c, dopamine D_1-4, histamine H₁, and alpha₁-adrenergic receptors.
Olanzapine shows moderate antagonism of 5-HT₃ and muscarinic M_1-5 receptors, and weak binding to GABA-A, benzodiazepines, and beta-adrenergic receptors.
Although the precise mechanism of action in schizophrenia and bipolar disorder is not known, the efficacy of olanzapine is thought to be mediated through combined antagonism of dopamine and serotonin type 2 receptor sites.
Pharmacokinetics: Onset of Action: Within 1-2 weeks for control of aggression, agitation, insomnia; 3-6 weeks for control of mania and positive psychotic symptoms. Adequate trial: Typically, 6 weeks at maximum tolerated doses.
Absorption: Olanzapine is well absorbed following oral administration. Olanzapine concentrations occurred peak plasma in approximately 6 hours (range: 5-8 hours) and achieved to steady state after approximately 7 days of continuous dosing and are approximately twice those observed following single-dose administration. Food does not appear to affect GI absorption of Olanzapine.
Distribution: The apparent volume of distribution of the drug averaged 1150 L and ranged from 660 to 1790 L for the 5^th to 95^th percentiles.
Olanzapine is 93% bound to plasma proteins over the concentration range of 7-1100 ng/mL, principally to albumin and α₁-acid glycoprotein.
Olanzapine and its glucuronide metabolite have been shown to cross the placenta in humans.
Olanzapine is distributed into milk.
Metabolism: Highly metabolized via direct glucuronidation and cytochrome P450 mediated oxidation (CYP1A2, CYP2D6); 40% removed via first pass metabolism.
Elimination: Olanzapine, 7% of the dose was recovered in urine as unchanged drug. Approximately 57% and 30% of the dose was recovered in the urine and feces, respectively. After multiple dose of Olanzapine, the principal circulating metabolites are the 10-N-glucuronide, which is present at steady state at 44% of the plasma concentration of the parent drug, and 4'-N-Desmethyl Olanzapine, which is present at steady state at 31% of the plasma concentration of Olanzapine.
The apparent plasma clearance of Olanzapine ranges from 12-47 L/hour (mean: 25 L/hour).
The clearance of Olanzapine in smokers is approximately 40% higher than in non-smokers.
The clearance of Olanzapine in females may be reduced by approximately 30% compared with males.
The elimination half-life of orally administered Olanzapine was 1.5 times longer in healthy geriatric individuals 65 years of age or older than in healthy younger adults.
Olanzapine is not appreciably removed by hemodialysis, probably due to its large volume of distribution and extensive protein binding.

Olanzapine is indicated for the acute and maintenance treatment of schizophrenia and other psychoses where positive symptoms (e.g. delusions, hallucinations, disordered thinking, hostility, and suspiciousness) and/or negative symptoms (e.g. flattened affect, emotional and social withdrawal, poverty of speech) are prominent. Olanzapine also alleviates the secondary affective symptoms commonly associated with schizophrenia and related disorder.
Olanzapine is effective in maintaining the clinical improvement during continuing therapy in patients who have shown an initial treatment response.
Olanzapine is indicated for the treatment of moderate or severe manic episode.
In patients whose manic episode has responded to olanzapine treatment, olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder.

Adult: Schizophrenia: The recommended starting dose for olanzapine is 10 mg/day.
Manic Episode: The starting dose is 15 mg as a single daily dose in monotherapy or 10 mg daily in combination therapy.
Preventing recurrence in bipolar disorder: The recommended starting dose is 10 mg/day. For patients who have been receiving olanzapine for treatment of manic episode, continue therapy for preventing recurrence at the same dose. If a new manic, mixed, or depressive episode occurs, olanzapine treatment should be continued (with dose optimization as needed), with supplementary therapy to treat mood symptoms, as clinically indicated.
During treatment for schizophrenia, manic episode and recurrence prevention in bipolar disorder, daily dosage may subsequently be adjusted on the basis of individual clinical status within the range 5-20 mg/day. An increase to a dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours. Olanzapine can be given without regards for meals as absorption is not affected by food. Gradual tapering of the dose should be considered when discontinuing olanzapine.
Children: There is no experience in children.
Elderly patients: A lower starting dose (5 mg/day) is not routinely indicated but should be considered for those 65 and over when clinical factors warrant.
Patients with renal and/or hepatic impairment: A lower starting dose (5 mg) should be considered for such patients. In case of moderate hepatic insufficiency (cirrhosis, Child-Pugh class A or B), the starting dose should be 5 mg and only increase with caution.
Gender: The starting dose and dose range need not be routinely altered for female patients relative to male patients.
Smokers: The starting dose and dose range need not be routinely altered for non-smokers relative to smokers.
When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the starting dose. Dose escalation, when indicated, should be conservative in such patients.
Mode of Administration: Olanzapine may be taken without regard to meals. When olanzapine is used in combination with fluoxetine, administer in the evening.

Overdose and Treatment: There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard procedures for management of overdose may be indicated (i.e. gastric lavage, administration of activated charcoal). The concomitant administration of activated charcoal was shown to reduce the oral bioavailability of olanzapine by 50-60%.
Use the multiple-dose activated charcoal, hemoperfusion, forced diuresis, and urinary alkalinization, is lacking; however, these treatments are unlikely to be beneficial following olanzapine overdosage because of the drug's large volume of distribution and extensive protein binding.
Symptomatic treatment and monitoring of vital organ function should be instituted according to clinical presentation, including treatment of hypotension and circulatory collapse and support of respiratory function.

Hypersensitivity to olanzapine or any component of the formulation.
Olanzapine is not approved for the treatment of patients with dementia-related psychosis.
Olanzapine is not approved for the treatment of Alzheimer's Disease.
Avoid herbal supplement or alcohol while receiving the olanzapine.
Patients with known risk of narrow-angle glaucoma.

When olanzapine is used in combination with fluoxetine, the usual contraindications associated with fluoxetine must be considered.
When olanzapine is used as adjunctive therapy with lithium or valproate, should be advised clinicians to refer to prescribing information for those other drugs.
Seizures: Seizures occurred in about 0.9%. Olanzapine should be administered with caution to patients with a history of seizures, patients with conditions known to lower the seizure threshold (e.g. dementia of the Alzheimer's type), and during concurrent therapy with drugs that may lower the seizure threshold.
ECG Changes: Olanzapine-treated patients experience potentially important ECG changes, including QT, QT_c (Fridericia corrected), and PR intervals. The higher dosage of the drug may increase the risk of QT_c internal prolongation; however, the clinical relevance of these findings remains to be established.
Chest Pain: In short-term trials, chest pain occurred in approximately 3% of patients.
Venous thromboembolic effects: Venous thromboembolic effects including pulmonary embolism and deep venous thrombosis, have been reported in patients receiving Olanzapine during post-marketing surveillance.
Hepatic Effect: Olanzapine therapy was associated with asymptomatic elevations in serum aminotransferase (transaminase) concentrations, including elevations in serum concentrations of ALT (SGPT), AST (SGOT), and γ-glutamyltransferase (GGT).
Olanzapine should be used with caution in patients with signs and symptoms of hepatic impairment, in patients pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated concurrently with potentially hepatotoxic drugs.
Weight Gain: Olanzapine have been associated with metabolic changes, including weight gain. Such metabolic changes may be associated with increased cardiovascular and cerebrovascular risk.
Dyslipidemia: Olanzapine has been associated with undesirable changes in serum lipid parameters, including elevations in serum triglyceride and cholesterol concentrations.
Endocrine and Metabolic: Olanzapine has been reported associated with peripheral edema in approximately 3%. Olanzapine increased bilirubin serum alkaline phosphatase concentrations and decreased proteinemia, which have been reported in at least 1% in short term treatment.
Laboratory Test Monitoring: Recommends fasting blood glucose testing and lipid profile determinations at the beginning of Olanzapine therapy and periodically during treatment with the drug.
Hyperprolactinemia: Olanzapine can cause elevated serum prolactin concentrations, which may persist during chronic use of the drug. Clinical disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been associated with prolactin-elevating drugs. In addition, chronic hyperprolactinemia associated with hypogonadism may lead to decrease bone density.
If Olanzapine therapy is considered in a patient with previously detected breast cancer, that approximately one-third of human breast cancers are prolactin-dependent in vitro.
Drug Reaction with Eosinophilia and Systemic Symptoms: Drug reaction with eosinophilia and systemic symptoms (dermatologic and sensitivity reaction) has been reported.
Dysphagia: Esophageal dysmotility and aspiration have been associated with the use of antipsychotic agents. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advance Alzheimer's disease. Olanzapine is not approved for the treatment of Alzheimer's disease.
Patients with Concomitant Illness: Olanzapine has demonstrated anticholinergic activity in vitro and constipation, dryness of the mouth, and tachycardia, possibly related to the drug's anticholinergic effects, have occurred. Olanzapine should be used with caution in patients with clinically important prostatic hypertrophy, angle-closure glaucoma, or a history of paralytic ileus or related conditions.
Concomitant Medication or Alcohol Use: Recommends that patients be advised to avoid herbal supplement or alcohol while receiving the Olanzapine.
Tardive Dyskinesia: Olanzapine should be prescribed in a manner that is most likely to minimize the occurrence of the tardive dyskinesia that is potentially irreversible, involuntary, dyskinetic movements.
Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia, and agranulocytosis temporally related to Olanzapine treatment that have been reported.
Orthostatic Hypotension: Orthostatic hypotension associated with dizziness, tachycardia, bradycardia, and/or syncope, particular during the initial dosage has been reported. Should be used with particular caution in patients with known cardiovascular disease (e.g., history of myocardial infraction or ischemia, heart failure, conduction abnormalities), cerebrovascular disease, and/or other conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy).
Hyperglycemia and Diabetes Mellitus: Hyperglycemia, sometimes severe and associated with ketoacidosis, hyperosmolar coma, or death, has been reported.
Neuroleptic Malignant Syndrome (NMS): A potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment has been reported.
Suicide: Possibility of a suicide attempt is inherent in patients with schizophrenia and bipolar disorder, close supervision of high risk patients is recommended during olanzapine therapy.
Use in the Elderly: Geriatric Patients with Dementia-Related Psychosis: Olanzapine is not approved for the treatment of patients with dementia-related psychosis.

Pregnancy Category: C.
Pregnancy: Olanzapine exposure during pregnancy need to be evaluated to more fully determine the relative safety of olanzapine and other antipsychotic agents when administered during pregnancy.
Lactation: Olanzapine is distributed into milk. The mean dosage received by an infant at steady state is estimated to be about 1.8% of the maternal dosage. The women who receiving olanzapine should not breast-feed.

Central and autonomic nervous system: abnormal gait, articulation impairment, drowsiness, extrapyramidal reaction, headache, hypertonia, insomnia, parkinsonian-like syndrome (tremor), restlessness.
Cardiovascular system: chest pain, hypertension, orthostatic hypotension, peripheral edema.
GI: abdominal pain, constipation, diarrhea, dyspepsia, increased appetite, vomiting, xerostomia.
Endocrine and Metabolic: weight gain, breast changes (enlargement, galactorrhea, gynecomastia, lactation disorder, increased gamma-glutamyl transferase, increased uric acid), menstrual disease (amenorrhea, hypomenorrhea, delayed menstruation, oligomenorrhea).
Genitourinary: sexual disorder, urinary incontinence, urinary tract infection.
Hepatic: decreased serum bilirubin, increased liver enzymes, increased serum alkaline phosphatase, increased serum ALT, increased serum AST.
Neuromuscular and skeletal: arthralgia, back pain, dyskinesia, limb pain, muscle rigidity, tremor, weakness.
Ophthalmic: Amblyopia, dry eyes, accommodation abnormality, mydriasis.
Respiratory: cough, epistaxis, nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, dyspnea, hyperventilation, lung edema.
Dermatologic and Sensitivity Reactions: Alopecia and photosensitivity. Allergic/hypersensitivity reaction (e.g. anaphylactoid reaction, angioedema, pruritus, urticarial, rash). Eruptive xanthomas, which are associated with hyperlipidemia. Leukocytoclastic vasculitis also has been reported in a geriatric patient receiving olanzapine and warfarin concurrently.

Metabolism/Transport Effects: Substrates of CYP1A2, CYP2D6.
Avoid Concomitant Use: Aclidinium, Amisulpride, Azelastine (Nasal), Benzodiazepines, Cimetropium, Eluxadoline, Glucagon, Glycopyrrolate, Ipratropium, Levosulpiride, Metoclopramide, Nitroglycerin, Orphenadrine, Oxatomide, Oxomemazine, Paraldehyde, Piribedil, Potassium Chloride, Sulpiride, Thalidomide, Tiotropium, Umeclidinium.
The levels/effects of Olanzapine may be increased by: Abiraterone acetate, Acetylcholinesterase inhibitors, Aclidinium, Blood pressure lowering agents, Brimonidine, Cannabis, Chloral betaine, Chlormethiazole, Chlorphenesin, Carbamate, CYP1A2 inhibitors, Deferasirox, Dimethindene, Doxylamine, Dronabinol, Droperidol, Fluvoxamine, Hydroxyzine, Ipratropium, Kava kava, Lamotrigine, Lithium, Lofexidine, Magnesium sulfate, Methotrimeprazine, Mifepristone, Monocycline, Nabilone, Obeticholic acid, Oxatomide, Oxomemazine, Peginterferon Alfa-2b, Perampanel, Pramlintide, Rufinamide, Serotonin modulators, Sodium oxybate, Tapentadol, Tetrahydrocannabinol, Trimeprazine, Umeclidinium, Vemurafenib.
Olanzapine may increase the levels/effects of: Abobotulinumtoxin A, Ethyl Alcohol, Amisulpride, Analgesics (Opioid), Anticholinergic Agents, Azelastine (Nasal), Benzodiazepines, Blonanserin, Buprenorphine, Cimetropium, CloZAPine, CNS Depressants, Eluxadoline, Glucagon, Glycopyrrolate (Oral Inhalation), Highest Risk QTc-Prolonging Agents, HYDROcodone, Iohexol, Iomeprol, Iopamidol, Mequitazine, Methotrimeprazine, Methylphenidate, MetyroSINE, Mirabegron, Mirtazapine, Moderate Risk QTc-Prolonging Agents, Onabotulinumtoxin A, Orphenadrine, OxyCODONE, Paraldehyde, Potassium Chloride, Ramosetron, Rimabotulinumtoxin B, Selective Serotonin Reuptake Inhibitors, Serotonin Modulators, Sulpiride, Suvorexant, Thalidomide, Thiazide and Thiazide-Like Diuretics, Tiotropium, TiZANidine, Topiramate, Zolpidem.
The levels/effects of Olanzapine may be decreased by: Acetylcholinesterase inhibitors, Antihepaciviral combination products, Cannabis, CYP1A2 inducers, Cyproterone, Lithium, Piribedil, Ritonavir, Teriflunomide, Valproate products.
Olanzapine may decrease the levels/effects of: Acetylcholinesterase Inhibitors, Amphetamines, Antidiabetic Agents, Anti-Parkinson Agents (Dopamine Agonist), Gastrointestinal Agents (Prokinetic), Itopride, Levosulpiride, Nitroglycerin, Piribedil, Quinagolide, Secretin.
Anticholinergic Agents: Olanzapine should be used with caution in patients concurrently receiving other drugs with anticholinergic activity.
Levodopa and Dopamine Agonists: Olanzapine may antagonize the effects of levodopa and dopamine agonists.
Lamotrigine: Olanzapine did not substantially alter lamotrigine pharmacokinetics when the drugs were administered concurrently. The tolerability of this combination was found to be similar to that of olanzapine alone, with mild sedative effects reported in some patients receiving the drug concurrently. Adjustment in Lamotrigine dosage may be necessary in some patients for therapeutic reasons when olanzapine therapy is initiated or discontinued.
Other CNS-Active Agents: The concomitant use of olanzapine with CNS agents (e.g. diazepam) that are associated with hypotension may potentiate the orthostatic hypotension associated with olanzapine.
Alcohol: The concomitant use of olanzapine with alcohol potentiated the orthostatic hypotension associated with olanzapine. Therefore, states of alcohol should be avoided during olanzapine therapy.
Hypotensive Agents: Olanzapine therapy potentially may enhance the effects of certain hypotensive agents during concurrent use. In addition, the administration of dopamine, epinephrine, and/or other sympathomimetic agents with β-agonist activity should be avoided in the treatment of olanzapine-induced hypotension.
Activated Charcoal: Concurrent administration of activated charcoal reduced peak plasma concentrations of olanzapine by approximately 60%.
Smoking: Plasma olanzapine concentrations generally are lower in smokers than in non-smoker.

Store below 30°C, protect from light.

Antipsychotics

N05AH03 - olanzapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics

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