being unable to get an erection at any time. Given these considerations, olanzapine should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. A ZYPREXA RELPREVV dose of 300 mg olanzapine injected every two weeks . Since olanzapine has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that olanzapine therapy does not affect them adversely [see Patient Counseling Information ( 17)]. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents. In premarketing trials involving more than 3100 patients and/or normal subjects, accidental or intentional acute overdosage of olanzapine was identified in 67 patients. Lorazepam injection should not be used to reconstitute olanzapine for injection IntraMuscular as this combination results in a delayed reconstitution time. Cerebrovascular Adverse Events (CVAE), Including Stroke Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in trials of olanzapine in elderly patients with dementia-related psychosis. Intramuscular Administration olanzapine for injection results in rapid absorption with peak plasma concentrations occurring within 15 to 45 minutes. Olanzapine is present in human milk. Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking olanzapine for injection as monotherapy. Inducers of CYP1A2 or Glucuronyl Transferase Omeprazole and rifampin may cause an increase in olanzapine clearance. Olanzapine Monotherapy in Adolescents: In placebo-controlled clinical trials of adolescent patients with schizophrenia or bipolar I disorder (manic or mixed episodes), greater frequencies for the following treatment-emergent findings, at anytime, were observed in laboratory analytes compared to placebo: elevated ALT (3X ULN in patients with ALT at baseline <3X ULN), (12% vs 2%); elevated AST (28% vs 4%); low total bilirubin (22% vs 7%); elevated GGT (10% vs 1%); and elevated prolactin (47% vs 7%). Administration of olanzapine for injection Olanzapine for injection IntraMuscular is intended for intramuscular use only. Somnolence was a commonly reported adverse reaction associated with olanzapine treatment, occurring at an incidence of 26% in olanzapine patients compared to 15% in placebo patients. Two currently available short-acting IM SGAs are olanzapine and ziprasidone. Olanzapine Monotherapy in Adolescents The safety and efficacy of olanzapine have not been established in patients under the age of 13 years. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with previously detected breast cancer. Mutagenesis No evidence of genotoxic potential for olanzapine was found in the 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. Mean increases in blood glucose have been observed in patients treated (median exposure of 9.2 months) with olanzapine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). An injection of a larger dose produces a dose-proportional increase in the systemic exposure. Clinical Trials in Adolescent Patients (age 13 to 17 years) Siddipet, Telangana-502281, India. In an open-label clinical pharmacology study in nonagitated patients with schizophrenia in which the safety and tolerability of intramuscular olanzapine were evaluated under a maximal dosing regimen (three 10 mg doses administered 4 hours apart), approximately one-third of these patients experienced a significant orthostatic decrease in systolic blood pressure (i.e., decrease 30 mmHg) [see Dosage and Administration ( 2.4)]. Zyprexa IntraMuscular injection is to be given only by or under the direct supervision of a doctor. Based on the pharmacologic action of olanzapine (D 2 receptor antagonism), treatment with olanzapine may result in an increase in serum prolactin levels, which may lead to a reversible reduction in fertility in females of reproductive potential [see Warnings and Precautions ( 5.15)]. Oral Administration, Monotherapy Olanzapine is well absorbed and reaches peak concentrations in approximately 6 hours following an oral dose. There is no general agreement about specific pharmacological treatment regimens for NMS. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic, and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. It is important to emphasize that, although the reactions occurred during treatment with olanzapine, they were not necessarily caused by it. In post marketing experience, the risk for severe adverse reactions (including fatalities) was increased with concomitant use of anticholinergic medications [see Drug Interactions ( 7.1)]. Olanzapine LAI has not been studied in elderly patients and therefore is not recommended for this treatment population unless a well . Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance. Fasting blood glucose testing and lipid profile at the beginning of, and periodically during, treatment is recommended [see Warnings and Precautions ( 5.5) and Patient Counseling Information ( 17)]. In the patient taking the largest identified amount, 300 mg, the only symptoms reported were drowsiness and slurred speech. Laboratory Changes The results of the trials follow: Olanzapine may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. Rats were dosed for 2 years at doses of 0.25, 1, 2.5, 4 mg/kg/day (males) and 0.25, 1, 4, 8 mg/kg/day (females) (equivalent to 0.13 to 2 and 0.13 to 4 times the daily oral MRHD based on mg/m 2 body surface area, respectively). Among less commonly reported symptoms were the following potentially medically serious reactions: aspiration, cardiopulmonary arrest, cardiac arrhythmias (such as supraventricular tachycardia and 1 patient experiencing sinus pause with spontaneous resumption of normal rhythm), delirium, possible neuroleptic malignant syndrome, respiratory depression/arrest, convulsion, hypertension, and hypotension. Diestrous was prolonged and estrous delayed at 1.1 mg/kg/day (0.6 times the daily oral MRHD based on mg/m 2 body surface area); therefore olanzapine may produce a delay in ovulation. Package insert / product label The patients initially received 50 mg sildenafil at baseline. Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. Increased Mortality Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. 1 Stuttering was only studied in oral and long acting injection (LAI) formulations. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. Elderly patients with dementia-related psychosis treated with olanzapine are at an increased risk of death compared to placebo. The clearance in young smoking males, for example, may be 3 times higher than that in elderly nonsmoking females. It is approved for maintenance treatment of schizophrenia in adults sufficiently stabilised during acute treatment with oral olanzapine. Appropriate educational placement is essential and psychosocial intervention is often helpful. In postmarketing reports of overdose with olanzapine alone, symptoms have been reported in the majority of cases. a Percentage of patients with a Simpson-Angus Scale total score >3. Olanzapine may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia and, in some patients, syncope, especially during the initial dose-titration period, probably reflecting its 1-adrenergic antagonistic properties [see Patient Counseling Information ( 17)]. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported with olanzapine exposure. Fetal/Neonatal adverse reactions Bipolar I Disorder (Manic or Mixed Episodes), Olanzapine as Adjunct to Lithium or Valproate In a study of patients who were already tolerating either lithium or valproate as monotherapy, discontinuation rates due to adverse reactions were 11% for the combination of oral olanzapine with lithium or valproate compared to 2% for patients who remained on lithium or valproate monotherapy. The olanzapine exposure after doses of ZYPREXA RELPREVV corresponds to exposure for oral doses of olanzapine. In placebo-controlled olanzapine clinical studies (up to 12 weeks), changes from normal to high in prolactin concentrations were observed in 30% of adults treated with olanzapine as compared to 10.5% of adults treated with placebo. In 5 placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis (n=1184), the following adverse reactions were reported in olanzapine-treated patients at an incidence of at least 2% and significantly greater than placebo-treated patients: falls, somnolence, peripheral edema, abnormal gait, urinary incontinence, lethargy, increased weight, asthenia, pyrexia, pneumonia, dry mouth and visual hallucinations. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects. Because olanzapine for injection has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that olanzapine for injection therapy does not affect them adversely [see Warnings and Precautions ( 5.12)]. Olanzapine administration was also associated with increases in serum prolactin [see Warnings and Precautions ( 5.15)], with an asymptomatic elevation of the eosinophil count in 0.3% of patients, and with an increase in CPK. Race In vivo studies have shown that exposures are similar among Japanese, Chinese and Caucasians, especially after normalization for body weight differences. 2 Adjusted for gender. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. Patient assessments were conducted during the 24 hours following the initial dose of intramuscular olanzapine for injection. 2 It is given by deep intramuscular (IM) gluteal injection every 2 or every 4 weeks. If agitation warranting additional intramuscular doses persists following the initial dose, subsequent doses up to 10 mg may be given. Little clinical trial data is available on weight gain in adolescents with olanzapine beyond 6 months of treatment. This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) for which occurred at a rate equal to or less than placebo. If signs and symptoms of tardive dyskinesia appear in a patient on olanzapine, drug discontinuation should be considered. Lorazepam (IM) Administration of intramuscular lorazepam (2 mg) 1 hour after intramuscular olanzapine for injection (5 mg) did not significantly affect the pharmacokinetics of olanzapine, unconjugated lorazepam, or total lorazepam. Epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. Olanzapine Monotherapy in Adults In an analysis of 5 placebo-controlled olanzapine monotherapy studies with treatment duration up to 12 weeks, olanzapine-treated patients had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.3 mg/dL, 3.0 mg/dL, and 20.8 mg/dL respectively compared to decreases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 6.1 mg/dL, 4.3 mg/dL, and 10.7 mg/dL for placebo-treated patients. Olanzapine for injection IntraMuscular reconstituted with Sterile Water for Injection should be used immediately (within 1 hour) after reconstitution. In the limited number of patients who were evaluated in hospitals, including the patient taking 300 mg, there were no observations indicating an adverse change in laboratory analytes or ECG. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Dosing modification may be necessary in patients who exhibit a combination of factors that may result in slower metabolism of olanzapine [see Dosage and Administration ( 2)]. The information below for olanzapine is derived from a clinical trial database for olanzapine consisting of 10,504 adult patients with approximately 4765 patient-years of exposure to olanzapine plus 722 patients with exposure to intramuscular olanzapine for injection. 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