"Feb. 23, 2012 -- The FDA has warned that treatment with antipsychotic drugs increases the risk of death among elderly patients with dementia, and now a new study confirms that some drugs are riskier than others.
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ZYPREXA RELPREVV is available only through a restricted distribution program [see WARNINGS AND PRECAUTIONS]. ZYPREXA RELPREVV must not be dispensed directly to a patient. For a patient to receive treatment, the prescriber, healthcare facility, patient, and pharmacy must all be enrolled in the ZYPREXA RELPREVV Patient Care Program. To enroll, call 1-877-7729390.
ZYPREXA RELPREVV is indicated for the treatment of schizophrenia. Efficacy was established in two clinical trials in patients with schizophrenia: one 8-week trial in adults and one maintenance trial in adults [see Clinical Studies].
DOSAGE AND ADMINISTRATION
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 Intra Muscular (10 mg/vial) is a short-acting formulation and should not be confused with ZYPREXA RELPREVV. Refer to the package insert for ZYPREXA Intra Muscular 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.
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 405 mg/4 weeks||150 mg/2 weeks or 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, and OVERDOSAGE]. Patients should be informed of this risk and how to recognize related symptoms [see PATIENT INFORMATION]. 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].
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, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].
ZYPREXA RELPREVV has not been studied in subjects under 18 years of age [see WARNINGS AND PRECAUTIONS].
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.
Instructions to Reconstitute and Administer ZYPREXA RELPREVV
For deep intramuscular gluteal injection only. Not to be injected intravenously or subcutaneously.
Step 1: Preparing Materials
Convenience kit includes:
- 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
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 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 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-use only.
Dosage Forms And Strengths
ZYPREXA RELPREVV is a powder for suspension for intramuscular use only. ZYPREXA RELPREVV is present as a yellow solid in a glass vial equivalent to 210, 300, or 405 mg olanzapine per vial. The diluent is a clear, colorless to slightly yellow solution in a glass vial [see DESCRIPTION and Storage and Handling]. The reconstituted suspension will be yellow and opaque [see DOSAGE AND ADMINISTRATION].
ZYPREXA RELPREVV convenience kit is supplied in single-use cartons. Each carton includes one vial of olanzapine pamoate monohydrate in dosage strengths that are equivalent to 210 mg olanzapine (483 mg olanzapine pamoate monohydrate), 300 mg olanzapine (690 mg olanzapine pamoate monohydrate), and 405 mg olanzapine (931 mg olanzapine pamoate monohydrate) per vial; one vial of approximately 3 mL of diluent for ZYPREXA RELPREVV used to suspend the drug product; one 3-mL syringe with pre-attached 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro needle with needle protection device; and two 19-gauge, 1.5- inch (38 mm) Hypodermic Needle-Pro needles with needle protection device.
Needle-Pro® is a registered trademark of Smiths Medical.
NDC 0002-7635-11 — single-use convenience kit: 210 mg vial (VL7635) with rust flip-off cap and 3-mL vial of sterile diluent (VL7622) with gray flip-off cap
NDC 0002-7636-11 — single-use convenience kit: 300 mg vial (VL7636) with olive flip-off cap and 3-mL vial of sterile diluent (VL7622) with gray flip-off cap
NDC 0002-7637-11 — single-use convenience kit: 405 mg vial (VL7637) with steel blue flip-off cap and 3-mL vial of sterile diluent (VL7622) with gray flip-off cap
Storage and Handling
ZYPREXA RELPREVV should be stored at room temperature not to exceed 30°C (86°F).
When the drug product is suspended in the solution for ZYPREXA RELPREVV, it may be held at room temperature for 24 hours. The vial should be agitated immediately prior to product withdrawal. Once the suspension is withdrawn into the syringe, it should be used immediately [see DOSAGE AND ADMINISTRATION].
Eli Lilly and Company, Indianapolis, IN 46285, USA
Last reviewed on RxList: 8/31/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Zyprexa Relprevv Information
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