About ZYPREXA® IntraMuscular
(olanzapine for Injection)
Rapid Efficacy
Rapid efficacy in agitation associated with schizophrenia within 15 minutes to help you restore calm quickly1,2
Rapid control of agitation associated with bipolar mania1,2
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No Patient Became Unarousable
No patient treated with ZYPREXA IntraMuscular in premarketing controlled clinical trials became unarousable (score of 9 on the Agitation-Calmness Evaluation Scale [ACES]).1*
Somnolence was the most common adverse event with ZYPREXA IntraMuscular in clinical trials.
No Incidence of Dystonia in Agitated Patients With Schizophrenia1
Dosing
| Dose | Injection volume |
|---|---|
| 10 mg | Withdraw total contents of vial |
| 7.5 mg | 1.5 mL |
| 5 mg | 1 mL |
| 2.5 mg | 0.5 mL |
| 10 mg is the recommended dose for agitation associated with bipolar mania and schizophrenia. | |
Follow the steps below to reconstitute and use ZYPREXA IntraMuscular:
- Inject 2.1 mL of Sterile Water for Injection into single-packaged vial for up to 10-mg dose.
- Dissolve contents of vial completely; resulting solution should be clear and yellow.
- Use solution within 1 hour; discard any unused portion.
- Refer to table for injection volumes and corresponding doses of ZYPREXA IntraMuscular.
- Immediately after use, dispose of syringe in approved sharps box.
Physical Incompatibility Information
ZYPREXA IntraMuscular should be reconstituted only with Sterile Water for Injection. ZYPREXA IntraMuscular should not be combined in a syringe with diazepam injection because precipitation occurs when these products are mixed. Lorazepam injection should not be used to reconstitute ZYPREXA IntraMuscular as this combination results in a delayed reconstitution time. ZYPREXA IntraMuscular should not be combined in a syringe with haloperidol injection because the resulting low pH has been shown to degrade olanzapine over time.
Recommended dose for agitation in schizophrenia or bipolar mania is 10 mg.
If clinically warranted, subsequent doses up to 10 mg may be given to agitated patients with schizophrenia or bipolar mania. However, the efficacy of repeated doses has not been systematically evaluated in controlled clinical trials. The safety of total daily doses greater than 30-mg or of 10-mg injections given more frequently than 2 hours after the initial dose and 4 hours after the second dose has not been evaluated in clinical trials. Maximal dosing (three 10-mg doses administered 2-4 hours apart) may be associated with substantial occurrence of significant orthostatic hypotension; it is recommended that patients requiring subsequent intramuscular injections be assessed for orthostatic hypotension prior to the administration of any subsequent doses. The administration of an additional dose to a patient with a clinically significant postural change in systolic blood pressure is not recommended.
Patients should remain recumbent if drowsy or dizzy after injection until examination has indicated that they are not experiencing postural hypotension and/or bradycardia.
Recommended dose for agitation in special populations is 2.5 mg to 5 mg.
A dose of 5 mg per injection should be considered for geriatric patients or when other clinical factors warrant. A lower dose of 2.5 mg per injection should be considered for patients who otherwise might be debilitated, predisposed to hypotensive reactions, or pharmacodynamically sensitive to olanzapine.
Patients should remain recumbent if drowsy or dizzy after injection until examination has indicated that they are not experiencing postural hypotension and/or bradycardia.
Following treatment with ZYPREXA IntraMuscular, patients with schizophrenia or bipolar mania can be transitioned to oral olanzapine when clinically indicated. Learn more about oral olanzapine.
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Methodology and Study Limitations
ZYPREXA IntraMuscular vs haloperidol IM and placebo IM: agitation in schizophrenia
A double-blind, multicenter trial involving 311 acutely agitated patients with a DSM-IV diagnosis of schizophrenia. Patients entering the trial had a minimum total score of 14 on the Positive and Negative Syndrome Scale Excited Component (PANSS-EC) with a score of ≥4 on at least one item (based on a 1–7 scale: 1=absent, 4=moderate, 7=extreme) and were judged by the clinical investigator as clinically agitated and appropriate candidates for IM medication. The primary efficacy measure was change from baseline to 2 hours post-injection on the PANSS-EC.
- Patients were randomly assigned to receive ZYPREXA IntraMuscular 10 mg per injection, haloperidol IM 7.5 mg per injection, or placebo IM. If clinically indicated, patients could receive up to 3 injections during the 24-hour treatment period, with a maximum cumulative dose of 30 mg ZYPREXA IntraMuscular or 22.5 mg haloperidol IM. The second injection, if required, could not be given until after the initial 2-hour period when the primary efficacy measure was assessed. The IM study period was followed by a 4-day oral treatment period during which patients continued with the formulation of the active IM treatment to which they had been assigned (dosage range 5-20 mg). Patients receiving placebo IM were transferred to oral olanzapine
- A similar double-blind, multicenter, dose-ranging trial involving 270 patients with a DSM-IV diagnosis of schizophrenia was also conducted. In this trial, patients were randomly assigned to receive injections of 2.5, 5, 7.5, or 10 mg ZYPREXA IntraMuscular; 7.5 mg haloperidol IM; or placebo IM. Entry criteria and primary efficacy measures were the same as in the fixed-dose trial
ZYPREXA IntraMuscular vs lorazepam IM and placebo IM: agitation in bipolar mania
A double-blind, multicenter trial involving 201 acutely agitated patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed. Patients entering the trial had a minimum total score of 14 on the PANSS-EC with a score of ≥4 on at least one item (based on a 1-7 scale: 1=absent, 4=moderate, 7=extreme) and were judged by the clinical investigator as clinically agitated and appropriate candidates for IM medication. The primary efficacy measure was change from baseline at 2 hours post-injection on the PANSS-EC.
- Patients were randomly assigned to receive ZYPREXA IntraMuscular 10 mg per injection, lorazepam IM 2 mg per injection, or placebo IM. If clinically indicated, patients could receive up to 3 injections during the 24-hour treatment period, with a maximum cumulative dose of 25 mg ZYPREXA IntraMuscular or 5 mg lorazepam IM. The second injection, if required, could not be given until after the initial 2-hour period when the primary efficacy measure was assessed
Lorazepam, a sedative and anxiolytic agent, is not indicated for the treatment of agitation.
Positive and Negative Syndrome Scale Excited Component
(PANSS-EC) is composed of 5 items from the PANSS that represent the core psychiatric symptoms prevalent in other scales designed to assess agitation, as follows: poor impulse control, tension, hostility, uncooperativeness, and excitement. Items are scored on a scale from 1 (absent) to 7 (extreme), for a total score ranging from 5 to 35.
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Increased Mortality in Elderly Patients With Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks) in these patients revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. 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. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. ZYPREXA® (olanzapine) is not approved for the treatment of elderly patients with dementia-related psychosis.
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Cerebrovascular adverse events (CVAE), including stroke, in elderly patients with dementia—Cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, were reported in trials of olanzapine in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of CVAE in patients treated with olanzapine compared to patients treated with placebo. Olanzapine is not approved for the treatment of elderly patients with dementia-related psychosis.
Hyperglycemia—Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including olanzapine. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics. Physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level. Patients taking olanzapine should be monitored regularly for worsening of glucose control. Persons with risk factors for diabetes who are starting on atypical antipsychotics should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.
Hyperlipidemia—Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and follow-up lipid evaluations in patients using olanzapine, is advised. Significant, and sometimes very high, elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use.
Weight Gain—Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.
Neuroleptic malignant syndrome (NMS)—As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with olanzapine. If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
Tardive dyskinesia (TD)—As with all antipsychotic medications, prescribing should be consistent with the need to minimize the risk of TD. The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.
Hemodynamic effects—In premarketing trials, some patients taking oral olanzapine experienced orthostatic hypotension associated with dizziness, tachycardia, and, in some cases, syncope (15/2500, 0.6%). Hypotension, bradycardia with or without hypotension, tachycardia, and, in some cases, syncope (2/722, 0.3%) were reported during the clinical trials of intramuscular olanzapine. In a clinical pharmacology study in non-agitated patients with schizophrenia, a regimen of three 10-mg doses administered 4 hours apart was associated with a significant orthostatic decrease in systolic blood pressure in approximately one-third of patients. Additional injections of intramuscular olanzapine are not recommended for patients with a clinically significant postural change in systolic blood pressure after the first dose.
Use caution in patients receiving other drugs that can induce hypotension, bradycardia, respiratory or central nervous system depression. Concomitant administration of intramuscular olanzapine and parenteral benzodiazepines has not been studied and is therefore not recommended. If this combination is considered, careful evaluation of clinical status for excessive sedation and cardiorespiratory depression is recommended.
Seizures—Occurred infrequently in premarketing clinical trials of oral olanzapine (22/2500, 0.9%). Oral olanzapine should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.
Effect on prolactin—Modest elevations of prolactin were seen with oral olanzapine in acute-phase schizophrenia trials (incidence 34% vs 13% with placebo), although mean changes from baseline to endpoint were not statistically significantly different between olanzapine and placebo. Some patients may have persisting modest prolactin elevations.
Transient, asymptomatic elevations of hepatic transaminase—In placebo-controlled schizophrenia studies, clinically significant ALT (SGPT) elevations (≥3 times the upper limit of the normal range) were observed in 2% (6/243) of patients exposed to oral olanzapine compared to none (0/115) of the placebo patients. None of these patients experienced jaundice. Rare postmarketing reports of hepatitis have been received. Very rare cases of cholestatic or mixed liver injury have also been reported in the postmarketing period. Periodic assessment of transaminases is recommended in patients with significant hepatic disease.
Special populations, elderly—Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Olanzapine should be used with caution in patients at risk for aspiration pneumonia. In 5 studies in elderly patients with dementia-related psychosis, adverse events reported more commonly with olanzapine than with placebo were falls, somnolence, peripheral edema, abnormal gait, urinary incontinence, lethargy, increased weight, asthenia, pyrexia, pneumonia, dry mouth, and visual hallucinations. Olanzapine should be used with caution in elderly patients with dementia. Olanzapine is not approved for treatment of patients with dementia-related psychosis.
Special populations, adolescents—The safety and efficacy of olanzapine have not been established in patients under the age of 18 years.
Drug interactions—Coadministration of lorazepam IM and intramuscular olanzapine added to the somnolence observed with either drug alone. Coadministration of diazepam or ethanol with olanzapine may potentiate orthostatic hypotension. Lower doses of olanzapine should be considered in patients receiving concomitant therapy with fluvoxamine.
Physical incompatibility information—Intramuscular olanzapine should be reconstituted only with Sterile Water for Injection. It should not be combined in a syringe with diazepam injection, with lorazepam injection, or with haloperidol injection. See the full Prescribing Information for more information.
Medication dispensing and prescribing errors have occurred between ZYPREXA® (olanzapine) and Zyrtec® (cetirizine HCl). These errors could result in unnecessary adverse events or potential relapse in patients suffering from schizophrenia or bipolar disorder. To reduce the potential for dispensing errors, please write ZYPREXA clearly.
The most common treatment-emergent adverse events associated with intramuscular olanzapine vs placebo IM in 24-hour trials involving agitated patients with schizophrenia or bipolar mania were somnolence (6% vs 3%), dizziness (4% vs 2%), hypotension (2% vs 0%), asthenia (2% vs 1%), tremor (1% vs 0%), and postural hypotension (1% vs 0%).
The most common treatment-emergent adverse events associated with oral olanzapine (vs placebo) in 6-week schizophrenia trials were somnolence (26% vs 15%), dizziness (11% vs 4%), weight gain (6% vs 1%), personality disorder (COSTART term for nonaggressive objectionable behavior; 8% vs 4%), constipation (9% vs 3%), akathisia (5% vs 1%), and postural hypotension (5% vs 2%).
The most common treatment-emergent adverse events associated with oral olanzapine (vs placebo) in 3- and 4-week bipolar mania trials were somnolence (35% vs 13%), dry mouth (22% vs 7%), dizziness (18% vs 6%), asthenia (15% vs 6%), constipation (11% vs 5%), dyspepsia (11% vs 5%), increased appetite (6% vs 3%), and tremor (6% vs 3%).
ZYRTEC is a registered trademark of UCB, SA.
For complete safety profile, see the full Prescribing Information
