ZYPREXA Relprevv

2 DOSAGE AND ADMINISTRATION 150 mg/2 wks, 300 mg/4 wks, 210 mg/2 wks, 405 mg/4 wks, or 300 mg/2 wks. See Table 1 for dosing recommendations. ( 2.1 ) ZYPREXA RELPREVV is intended for deep intramuscular gluteal injection only. Do not administer intravenously or subcutaneously. ( 2.1 ) Be aware that there are two ZYPREXA intramuscular formulations with different dosing schedules. ZYPREXA IntraMuscular (10 mg/vial) is a short-acting formulation and should not be confused with ZYPREXA RELPREVV. ( 2.1 ) Establish tolerability with oral olanzapine prior to initiating treatment. ( 2.1 ) ZYPREXA RELPREVV doses above 405 mg every 4 weeks or 300 mg every 2 weeks have not been evaluated in clinical trials. ( 2.1 ) Use in specific populations (including renal and hepatic impaired, and pediatric population) has not been studied. ( 2.1 ) Must be suspended using only the diluent for ZYPREXA RELPREVV provided in the convenience kit. ( 2.2 ) 2.1 Dosage ZYPREXA RELPREVV is intended for deep intramuscular gluteal injection only and should not be administered intravenously or subcutaneously. Be aware that there are two ZYPREXA intramuscular formulations with different dosing schedules. ZYPREXA IntraMuscular (10 mg/vial) is a short-acting formulation and should not be confused with ZYPREXA RELPREVV. Refer to the package insert for ZYPREXA IntraMuscular for more information about that product. Establish tolerability with oral olanzapine prior to initiating treatment. ZYPREXA RELPREVV should be administered by a healthcare professional every 2 to 4 weeks by deep intramuscular gluteal injection using a 19-gauge, 1.5-inch needle. Following insertion of the needle into the muscle, aspiration should be maintained for several seconds to ensure that no blood is drawn into the syringe. If any blood is aspirated into the syringe, it should be discarded and fresh drug should be prepared using a new convenience kit. The injection should be performed at a steady, continuous pressure. Do not massage the injection site. Dose Selection — The efficacy of ZYPREXA RELPREVV has been demonstrated within the range of 150 mg to 300 mg administered every 2 weeks and with 405 mg administered every 4 weeks. Dose recommendations considering oral ZYPREXA and ZYPREXA RELPREVV are shown in Table 1 . Table 1: Recommended Dosing for ZYPREXA RELPREVV Based on Correspondence to Oral ZYPREXA Doses Target Oral ZYPREXA Dose Dosing of ZYPREXA RELPREVV During the First 8 Weeks Maintenance Dose After 8 Weeks of ZYPREXA RELPREVV Treatment 10 mg/day 210 mg/2 weeks or 150 mg/2 weeks or 405 mg/4 weeks 300 mg/4 weeks 15 mg/day 300 mg/2 weeks 210 mg/2 weeks or 405 mg/4 weeks 20 mg/day 300 mg/2 weeks 300 mg/2 weeks ZYPREXA RELPREVV doses greater than 405 mg every 4 weeks or 300 mg every 2 weeks have not been evaluated in clinical trials. Post-Injection Delirium/Sedation Syndrome — During premarketing clinical studies, adverse events that presented with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma) and/or delirium, were reported in patients following an injection of ZYPREXA RELPREVV [see Boxed Warning , Warnings and Precautions ( 5.1 ), and Overdosage ( 10.1 )] . Patients should be informed of this risk and how to recognize related symptoms [see Patient Counseling Information ( 17 )] . ZYPREXA RELPREVV must be administered in a registered healthcare facility with ready access to emergency response services. After each ZYPREXA RELPREVV injection, a healthcare professional must continuously observe the patient at the healthcare facility for at least 3 hours for symptoms consistent with olanzapine overdose, including sedation (ranging from mild in severity to coma) and/or delirium (including confusion, disorientation, agitation, anxiety, and other cognitive impairment). Other symptoms noted include extrapyramidal symptoms, dysarthria, ataxia, aggression, dizziness, weakness, hypertension, and convulsion. The potential for onset of an event is greatest within the first hour. The majority of cases have occurred within the first 3 hours after injection; however, the event has occurred after 3 hours. Following the 3-hour observation period, healthcare professionals must confirm that the patient is alert, oriented, and absent of any signs and symptoms of post-injection delirium/sedation syndrome prior to being released. All patients must be accompanied to their destination upon leaving the facility. For the remainder of the day of each injection, patients should not drive or operate heavy machinery, and should be advised to be vigilant for symptoms of post-injection delirium/sedation syndrome and be able to obtain medical assistance if needed. If post-injection delirium/sedation syndrome is suspected, close medical supervision and monitoring should be instituted in a facility capable of resuscitation [see Overdosage ( 10 )] . Dosing in Specific Populations — Tolerance of oral ZYPREXA should be established prior to initiating treatment with ZYPREXA RELPREVV. The recommended starting dose is ZYPREXA RELPREVV 150 mg/4 wks in patients who are debilitated, who have a predisposition to hypotensive reactions, who otherwise exhibit a combination of factors that may result in slower metabolism of olanzapine (e.g., nonsmoking female patients ≥65 years of age), or who may be more pharmacodynamically sensitive to olanzapine. When indicated, dose escalation should be undertaken with caution in these patients [see Warnings and Precautions ( 5.18 ), Drug Interactions ( 7 ), and Clinical Pharmacology ( 12.3 )] . ZYPREXA RELPREVV has not been studied in subjects under 18 years of age [see Warnings and Precautions ( 5.7 )] . Maintenance Treatment — Although no controlled studies have been conducted to determine how long patients should be treated with ZYPREXA RELPREVV, efficacy has been demonstrated over a period of 24 weeks in patients with stabilized schizophrenia. Additionally, oral ZYPREXA has been shown to be effective in maintenance of treatment response in schizophrenia in longer-term use. Patients should be periodically reassessed to determine the need for continued treatment. Switching from Other Antipsychotics — There are no systematically collected data to specifically address how to switch patients with schizophrenia from other antipsychotics to ZYPREXA RELPREVV. 2.2 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

See official label

1 INDICATIONS AND USAGE ZYPREXA RELPREVV is available only through a restricted distribution program [see Warnings and Precautions ( 5.2 )] .