Olanzapine pamoate
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: POST-INJECTION DELIRIUM/SEDATION SYNDROME and INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS WARNING: POST-INJECTION DELIRIUM/SEDATION SYNDROME and INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Patients are at risk for severe sedation (including coma) and/or delirium after each injection and must be observed for at least 3 hours in a certified healthcare setting with ready access to emergency response services.
Because of this risk, ZYPREXA RELPREVV is available only through a restricted distribution program called ZYPREXA RELPREVV REMS and requires prescriber, healthcare setting, patient, and pharmacy enrollment. ( 2.1 , 5.1 , 5.2 , 10.2 , 17 ) Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ZYPREXA RELPREVV is not approved for the treatment of patients with dementia-related psychosis.
( 5.3 , 8.5 , 17 ) Post-Injection Delirium/Sedation Syndrome — Adverse events with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma) and/or delirium, have been reported following injections of ZYPREXA RELPREVV. ZYPREXA RELPREVV must be administered in a certified healthcare setting with ready access to emergency response services. After each injection, patients must be observed at the healthcare setting by a healthcare professional for at least 3 hours.
Because of this risk, ZYPREXA RELPREVV is available only through a restricted distribution program called ZYPREXA RELPREVV REMS and requires prescriber, healthcare setting, patient, and pharmacy enrollment [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.1 , 5.2 ), Overdosage ( 10.2 ), and Patient Counseling Information ( 17 )] . Increased Mortality in Elderly Patients with Dementia-Related Psychosis — Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death 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 (e.g., heart failure, sudden death)…
Dosing in kidney impairment
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.
Preparation and administration
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Instructions to Reconstitute and Administer ZYPREXA RELPREVV For deep intramuscular gluteal injection only. Not to be injected intravenously or subcutaneously. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Step 1: Preparing Materials Convenience kit includes: Single-dose vial of ZYPREXA RELPREVV powder 3-mL vial of diluent One 3-mL syringe with pre-attached 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro ® needle with needle protection device Two 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro needles with needle protection device— For obese patients, a 2-inch (50 mm), 19-gauge or larger needle (not included in convenience kit) may be used for administration.
ZYPREXA RELPREVV must be suspended using only the diluent supplied in the convenience kit. It is recommended that gloves are used when reconstituting, as ZYPREXA RELPREVV may be irritating to the skin. Flush with water if contact is made with skin. See additional insert entitled "Instructions to Reconstitute and Administer ZYPREXA RELPREVV" (included) for more information regarding the safe and effective use of the Hypodermic Needle-Pro syringe and needle.
Step 2: Determining Reconstitution Volume Refer to the table below to determine the amount of diluent to be added to powder for reconstitution of each vial strength. It is important to note that there is more diluent in the vial than is needed to reconstitute. Dose Vial Strength Diluent to Add 150 mg 210 mg 1.3 mL 210 mg 210 mg 1.3 mL 300 mg 300 mg 1.8 mL 405 mg 405 mg 2.3 mL Step 3: Reconstituting ZYPREXA RELPREVV Please read the Hypodermic Needle-Pro Instructions for Use before proceeding with Step 3.
Failure to follow these instructions may result in a needlestick injury. Loosen the powder by lightly tapping the vial. Open the prepackaged Hypodermic Needle-Pro syringe and needle with needle protection device. Withdraw the pre-determined diluent volume ( Step 2 ) into the syringe. Inject the diluent into the powder vial.
Withdraw air to equalize the pressure in the vial by pulling back slightly on the plunger in the syringe. Remove the needle from the vial, holding the vial upright to prevent any loss of material. Engage the needle safety device (refer to complete Hypodermic Needle-Pro Instructions for Use). Pad a hard surface to cushion impact ( see Figure 1 ).
Tap the vial firmly and repeatedly on the surface until no powder is visible. Figure 1: Tap firmly to mix. Visually check the vial for clumps. Unsuspended powder appears as yellow, dry clumps clinging to the vial. Additional tapping may be required if large clumps remain ( see Figure 2 ). Figure 2: Check for unsuspended powder and repeat tapping if needed.
Shake the vial vigorously until the suspension appears smooth and is consistent in color and texture. The suspended product will be yellow and opaque ( see Figure 3 ). Figure 3: Vigorously shake vial. If foam forms, let vial stand to allow foam to dissipate. If the product is not used right away, it should be shaken vigorously to re-suspend.
Reconstituted ZYPREXA RELPREVV remains stable at room temperature for up to 24 hours in the vial. Step 4: Injecting ZYPREXA RELPREVV Before administering the injection, confirm there will be someone to accompany the patient after the 3-hour observation period. If this cannot be confirmed, do not give the injection. Refer to the table below to determine the final volume to inject.
Suspension concentration is 150 mg/mL ZYPREXA RELPREVV. Dose Final Volume to Inject 150 mg 1 mL 210 mg 1.4 mL 300 mg 2 mL 405 mg 2.7 mL Attach a new safety needle to the syringe. Slowly withdraw the desired amount into the syringe. Some excess product will remain in the vial. Engage the needle safety device and remove the needle from syringe.
For administration, select the 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro needle with needle protection device. For obese patients, a 2-inch (50 mm), 19-gauge or larger needle (not included in convenience kit) may be used. To help prevent clogging, a 19-gauge or larger needle must be used. Attach the new safety needle to the syringe prior to injection.
Once the suspension has been removed from the vial, it should be injected immediately. For deep intramuscular gluteal injection only. Do not inject intravenously or subcutaneously. Select and prepare a site for injection in the gluteal area. After insertion of the needle into the muscle, aspirate for several seconds to ensure that no blood appears .
If any blood is drawn into the syringe, discard the syringe and the dose and begin with a new convenience kit. The injection should be performed with steady, continuous pressure. Do not massage the injection site. Engage the needle safety device. Dispose of the vials, needles, and syringe appropriately after injection. The vial is for single-dose only.
Figure 1 Figure 2 Figure 3
| Dose | Vial Strength | Diluent to Add |
| 150 mg | 210 mg | 1.3 mL |
| 210 mg | 210 mg | 1.3 mL |
| 300 mg | 300 mg | 1.8 mL |
| 405 mg | 405 mg | 2.3 mL |
| Dose | Final Volume to Inject |
| 150 mg | 1 mL |
| 210 mg | 1.4 mL |
| 300 mg | 2 mL |
| 405 mg | 2.7 mL |
Drug interactions
Check olanzapine pamoate against a medication listLabel text (9 paragraphs)
Acting Drugs: Caution should be used when used in combination with other centrally acting drugs and alcohol. ( 7.2 ) Antihypertensive Agents: Enhanced antihypertensive effect. ( 7.2 ) Levodopa and Dopamine Agonists: May antagonize levodopa/dopamine agonists. ( 7.2 ) Diazepam: May potentiate orthostatic hypotension. ( 7.1 , 7.2 ) Alcohol: May potentiate orthostatic hypotension. ( 7.1 ) Carbamazepine: Increased clearance of olanzapine. ( 7.1 ) Fluvoxamine: May increase olanzapine levels. ( 7.1 )
7.1 Potential for Other Drugs to Affect Olanzapine Diazepam — The co-administration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine [see Drug Interactions ( 7.2 )] . Inducers of CYP1A2 — Carbamazepine therapy (200 mg bid) causes an approximately 50% increase in the clearance of olanzapine. This increase is likely due to the fact that carbamazepine is a potent inducer of CYP1A2 activity. Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance. Alcohol — Ethanol (45 mg/70 kg single dose) did not have an effect on olanzapine pharmacokinetics.
The co-administration of alcohol (i.e., ethanol) with olanzapine potentiated the orthostatic hypotension observed with olanzapine [see Drug Interactions ( 7.2 )] . Inhibitors of CYP1A2 — Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of olanzapine. This results in a mean increase in olanzapine Cmax following fluvoxamine of 54% in female nonsmokers and 77% in male smokers. The mean increase in olanzapine AUC is 52% and 108%, respectively. Lower doses of olanzapine should be considered in patients receiving concomitant treatment with fluvoxamine.
Inhibitors of CYP2D6 — Fluoxetine caused a small decrease in olanzapine clearance leading to a minimal change in olanzapine steady-state concentrations and, therefore dose modification is not routinely recommended. Warfarin — Warfarin (20 mg single dose) did not affect olanzapine pharmacokinetics [see Drug Interactions ( 7.2 )] . Inducers of CYP1A2 or Glucuronyl Transferase Enzymes — Omeprazole and rifampin may cause an increase in olanzapine clearance. Anticholinergic Drugs — Concomitant treatment with olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility.
ZYPREXA RELPREVV should be used with caution in patients receiving medications having anticholinergic (antimuscarinic) effects [see Warnings and Precautions ( 5.16 )] .
7.2 Potential for Olanzapine to Affect Other Drugs CNS Acting Drugs — Given the primary CNS effects of olanzapine, caution should be used when olanzapine is taken in combination with other centrally acting drugs and alcohol. Antihypertensive Agents — Olanzapine, because of its potential for inducing hypotension, may enhance the effects of certain antihypertensive agents. Levodopa and Dopamine Agonists — Olanzapine may antagonize the effects of levodopa and dopamine agonists. Lorazepam (IM) — Co-administration of lorazepam does not significantly affect the pharmacokinetics of olanzapine, unconjugated lorazepam, or total lorazepam.
However, this co-administration of lorazepam with olanzapine potentiated the somnolence observed with either drug alone. Lithium — Multiple doses of olanzapine (10 mg for 8 days) did not influence the kinetics of lithium. Therefore, concomitant olanzapine administration does not require dosage adjustment of lithium. Valproate — Olanzapine (10 mg daily for 2 weeks) did not affect the steady-state plasma concentrations of valproate. Therefore, concomitant olanzapine administration does not require dosage adjustment of valproate.
Effect of Olanzapine on Drug Metabolizing Enzymes — In vitro studies utilizing human liver microsomes suggest that olanzapine has little potential to inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. Thus, olanzapine is unlikely to cause clinically important drug interactions mediated by these enzymes. Imipramine — Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite desipramine. Warfarin — Single doses of olanzapine did not affect the pharmacokinetics of warfarin [see Drug Interactions ( 7.1 )] . Diazepam — Olanzapine did not influence the pharmacokinetics of diazepam or its active metabolite N-desmethyldiazepam.
However, diazepam co-administered with olanzapine increased the orthostatic hypotension observed with either drug given alone [see Drug Interactions ( 7.1 )] . Alcohol — Multiple doses of olanzapine did not influence the kinetics of ethanol [see Drug Interactions ( 7.1 )] . Biperiden — Multiple doses of olanzapine did not influence the kinetics of biperiden. Theophylline — Multiple doses of olanzapine did not affect the pharmacokinetics of theophylline or its metabolites.
Contraindications
None. None.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including ZYPREXA RELPREVV, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including ZYPREXA RELPREVV, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations) .
Overall available data from published epidemiologic studies of pregnant women exposed to olanzapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including ZYPREXA RELPREVV, during pregnancy (see Clinical Considerations) .
Olanzapine was not teratogenic when administered orally to pregnant rats and rabbits at doses that are 9- and 30-times the daily oral maximum recommended human dose (MRHD), based on mg/m 2 body surface area; some fetal toxicities were observed at these doses (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Disease-associated maternal and embryo/fetal risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors.
Fetal/Neonatal adverse reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including ZYPREXA RELPREVV, during the third trimester of pregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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