What should clinicians know about Zyprexa Relprevv (olanzapine for extended release injectable suspension)?

Zyprexa Relprevv is a long-acting injectable (LAI) formulation of Zyprexa (olanzapine). It is a second-generation antipsychotic LAI that can be administered every 2 or every 4 weeks. It is FDA-indicated for treatment of schizophrenia in adults.

Zyprexa Relprevv should not be confused with Zyprexa IntraMuscular (10 mg/vial), which is a short-acting formulation of Zyprexa.

Establishing tolerability

  • Prior to initiating Zyprexa Relprevv, establish tolerability with oral olanzapine.


  • 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.
  • Zyprexa Relprevv is a powder for suspension for intramuscular use only. 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 (injection volume of 1.4 ml) olanzapine (483 mg olanzapine pamoate monohydrate), 300 mg (injection volume of 2 ml) olanzapine (690 mg olanzapine pamoate monohydrate), and 405 mg (injection volume of 2.7 ml) 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.
  • 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 Once the suspension is withdrawn into the syringe, it should be used immediately.
  • Recommended dosing for Zyprexa Relprevv is based on correspondence to oral Zyprexa doses (see table below).
  • Treatment with Zyprexa Relprevv does not require additional loading dosing or oral supplementation.

    Dose Conversion of Oral Olanzapine to Olanzapine LAI

    PO Dose

    LAI/IM Dose – Initial 8 weeks

    LAI/IM Dose – Maintenance

    10 mg daily

    210mg every 2 weeks or
    405mg every 4 weeks

    150 mg every 2 weeks or
    300 mg every 4 weeks

    15 mg daily

    300 mg every 2 weeks

    210 mg every 2 weeks or
    405 mg every 4 weeks

    20 mg daily

    300 mg every 2 weeks

    300 mg every 2 weeks

    Recommended available dose formulations include 210 mg, 300 mg and 405 mg pre-filled powder for suspension vial kits.

    Dose reduction may be necessary for CYP450 interactions of side effect intolerance.

    1. Eli Lilly. (2019). Zyprexa Relprevv prescribing information
    2. American Psychiatric Association. (2020). The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. American Psychiatric Association Publishing. https://doi.org/10.1176/appi.books.9780890424841

Important warnings

Potential for development of Post-Injection Delirium/Sedation Syndrome:

  • This adverse reaction presents with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma) and/or delirium.
  • Patients should be informed of this risk and how to recognize related symptoms.
  • 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 in some cases.
  • 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 below – management).

Recently added to prescribing information for olanzapine oral and Zyprexa Relprevv (4/2020):

  • Anticholinergic (antimuscarinic) Effects: Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus or related conditions.

Practical issues

  •  Zyprexa Relprevv Patient Care Program (click to access) is designed to mitigate the risk of negative outcomes associated with Zyprexa Relprevv post-injection delirium/sedation syndrome (PDSS).         
  • It provides access to the required training for prescribers, healthcare facility staff, and pharmacy services providers. Once the training materials have been reviewed, the providers must complete the appropriate Registration Form and establish user account.
  • Zyprexa Relprevv Patient Care Program also allows access to the prescribing information, training materials, medication guide, the list of enrolled Pharmacy Service Providers, and contact information for Zyprexa Relprevv Patient Care Program Coordinating Center.

Management of Post-injection delirium/sedation syndrome

  • There is no specific antidote to olanzapine. Therefore, appropriate supportive measures should be initiated.
  • Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. (Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity, since beta stimulation may worsen hypotension in the setting of olanzapine-induced alpha blockade.)
  • Respiratory support, including ventilation, may be required. Close medical supervision and monitoring should continue until the patient recovers.
  • In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation, which may include intubation.
  • The possibility of obtundation (reduced level of consciousness), seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis.
  • Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias.
  • The possibility of multiple drug involvement should be considered.

FDA medication label

  • Information on this topic is found in the FDA medication label. Here is the most recent label, at time of writing.
  • Medication labels can be found by searching Drugs@FDA at the FDA website. Labels are also available using the Drugs@FDA app for Apple or Android devices. Labels change over time, and the current label should always be consulted.


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