How to Dilute Olanzapine Injection?

In a major European study of first-episode schizophrenia, olanzapine showed the lowest rate of treatment discontinuation (33%) compared to four other antipsychotics [1.8.3]. Understanding how to dilute olanzapine injection correctly is critical for safe administration by healthcare professionals.

Quick Summary

A detailed reference for healthcare professionals on the proper reconstitution procedures for olanzapine injections. It covers the crucial differences between the short-acting and long-acting (LAI) formulations, including specific diluents and volumes.

Key Points

• Two Formulations: Olanzapine injection has a short-acting (IM) and long-acting (LAI/Relprevv) form; they are not interchangeable and have different reconstitution protocols [1.4.3].

• Diluent Specificity: Short-acting olanzapine must only be reconstituted with Sterile Water for Injection [1.2.1, 1.5.1]. The long-acting (Relprevv) form must only be reconstituted with the specific diluent provided in its kit [1.2.4].

• Final Appearance: Reconstituted short-acting olanzapine is a clear, yellow solution [1.2.2], while the long-acting suspension is a yellow, opaque liquid [1.3.6].

• Administration Site: Long-acting olanzapine (Relprevv) must be injected only into the deep gluteal muscle, whereas the short-acting form can be injected into any large muscle mass [1.4.3, 1.2.1].

• Stability is Different: The short-acting solution must be used within one hour of reconstitution [1.6.2]. The long-acting suspension is stable for up to 24 hours in the vial but should be injected immediately once drawn into a syringe [1.6.4].

• Mandatory Observation: Patients receiving the long-acting Zyprexa Relprevv injection must be observed by a healthcare professional for at least 3 hours post-injection due to the risk of PDSS [1.4.3, 1.7.6].

Important Medical Disclaimer

This content is for informational purposes only and is intended for qualified healthcare professionals. The reconstitution and administration of olanzapine injection must only be performed by a licensed healthcare provider. Never attempt to self-administer this medication. Incorrect preparation or administration can lead to serious adverse effects.

Understanding Olanzapine Injections: Short-Acting vs. Long-Acting

Olanzapine for intramuscular (IM) use comes in two distinct forms that are not interchangeable: a short-acting formulation (often referred to as Zyprexa® IM) and a long-acting injectable (LAI), known as Zyprexa® Relprevv® [1.4.3]. The term 'dilute' is clinically referred to as 'reconstitution,' which is the process of mixing the medication powder with a specific liquid before injection. The procedures for these two forms are critically different.

Short-Acting Intramuscular (IM) Olanzapine

This formulation is used for the rapid control of agitation in patients with conditions like schizophrenia or bipolar mania [1.2.3, 1.4.5]. Its effects are immediate and last for a few hours. Treatment is typically for a maximum of three days before transitioning to oral therapy if needed [1.2.3].

Long-Acting Injectable (LAI) Olanzapine (Zyprexa Relprevv)

This is an extended-release suspension administered every 2 to 4 weeks for the maintenance treatment of schizophrenia [1.4.1, 1.4.3]. It provides a steady level of medication in the body over a prolonged period. This formulation has a strict post-injection protocol due to the risk of Post-injection Delirium/Sedation Syndrome (PDSS) [1.4.3].

Comparison of Olanzapine Injection Formulations

Feature	Short-Acting Olanzapine (Zyprexa® IM)	Long-Acting Olanzapine (Zyprexa® Relprevv®)
Indication	Rapid control of agitation [1.2.3]	Maintenance treatment of schizophrenia [1.4.3]
Diluent	Sterile Water for Injection ONLY [1.2.1, 1.5.1]	Special diluent provided in the kit ONLY [1.2.4, 1.3.7]
Reconstitution Volume	2.1 mL of Sterile Water for Injection for a 10 mg vial [1.2.1, 1.2.2]	Varies by dose (e.g., 1.8 mL for 300 mg vial) [1.2.4]
Final Appearance	Clear, yellow solution [1.2.1, 1.2.2]	Yellow, opaque suspension [1.2.5, 1.3.6]
Administration Site	Deep into the muscle mass [1.2.1, 1.2.3]	Deep intramuscular GLUTEAL injection ONLY [1.3.7, 1.4.3]
Stability After Reconstitution	Must be used within 1 hour [1.2.2, 1.6.2]	Stable in the vial for up to 24 hours at room temp [1.3.3, 1.6.4]
Post-Injection Observation	Recommended observation for 2-4 hours for side effects like hypotension [1.2.3]	MANDATORY observation for at least 3 hours by a healthcare professional in a registered facility [1.4.3, 1.7.6]

How to Reconstitute Short-Acting Olanzapine (10 mg vial)

Supplies Needed

• One 10 mg vial of Olanzapine for Injection powder
• Sterile Water for Injection
• One sterile syringe (3 mL)
• Appropriate needles for withdrawal and administration

Step-by-Step Instructions

1. Inspect the Vial: Visually inspect the vial to ensure the powder is present and there is no damage to the container [1.2.2].
2. Prepare the Diluent: Using a sterile syringe, withdraw exactly 2.1 mL of Sterile Water for Injection [1.2.1, 1.4.4]. Using any other diluent like lorazepam or diazepam injection is contraindicated as it can cause precipitation or delayed reconstitution [1.2.6, 1.4.5].
3. Inject Diluent: Inject the 2.1 mL of sterile water into the olanzapine powder vial [1.4.4].
4. Dissolve the Powder: Rotate the vial until the powder is completely dissolved. Do not shake vigorously. The resulting solution should be clear and yellow [1.2.2, 1.4.4]. This creates a solution with a concentration of 5 mg/mL [1.2.3].
5. Withdraw the Dose: Withdraw the required volume for the prescribed dose. For a 10 mg dose, withdraw the total contents of the vial. For a 5 mg dose, withdraw 1 mL [1.4.5].
6. Administer Immediately: The reconstituted solution must be used within 1 hour of preparation [1.2.2, 1.6.2]. Administer via deep intramuscular injection [1.2.3]. Do not administer intravenously or subcutaneously [1.4.5]. Discard any unused portion [1.2.2].

How to Reconstitute Long-Acting Olanzapine (Zyprexa Relprevv)

Supplies Needed

• The convenience kit, which includes the vial of olanzapine powder, a vial of the special diluent, a 3 mL syringe, and specific safety needles [1.3.7].

Step-by-Step Instructions

1. Prepare: Loosen the powder by lightly tapping the vial. Determine the correct volume of diluent to add based on the vial strength as specified in the package insert [1.3.5]. The diluent vial contains more liquid than is needed [1.3.7].
2. Add Diluent: Withdraw the specified amount of the provided diluent and inject it into the powder vial. Withdraw a small amount of air to equalize the pressure [1.3.5].
3. Mix Thoroughly: Engage the needle's safety device, then pad a hard surface and tap the vial firmly and repeatedly until all powder is dissolved and no yellow clumps are visible. This step is crucial [1.3.5, 1.3.6].
4. Suspend the Medication: After tapping, shake the vial vigorously until the suspension appears smooth, yellow, and opaque. If foam develops, let it dissipate [1.2.5, 1.3.6].
5. Prepare for Injection: Attach a new, appropriate gauge safety needle (typically 19-gauge or larger) to the syringe [1.3.7]. Withdraw the desired dose from the vial. The product should be injected immediately after being drawn into the syringe [1.6.4].
6. Administer: Administer as a deep intramuscular gluteal injection only. Aspirate for several seconds to ensure no blood enters the syringe. If blood appears, the entire kit must be discarded and a new one prepared [1.4.3]. Do not massage the injection site [1.3.7].

The Risk of Post-Injection Delirium/Sedation Syndrome (PDSS)

PDSS is a serious risk associated specifically with Zyprexa Relprevv (LAI) that presents like an olanzapine overdose [1.7.6]. It is believed to be caused by accidental intravascular injection of the medication [1.7.6]. Symptoms include dizziness, confusion, slurred speech, sedation, and can progress to coma [1.7.2, 1.7.3].

• The incidence is low, occurring in about 0.07% of injections [1.7.6].
• Most cases (over 90%) occur within the first hour after injection [1.7.1, 1.7.2].
• Due to this risk, patients must be observed at the healthcare facility for at least 3 hours after every injection [1.4.3].
• The patient must be alert, oriented, and free of symptoms before being released to an escort. They should not drive or operate heavy machinery for the rest of the day [1.7.6].

Conclusion

Knowing how to dilute olanzapine injection is a fundamental skill for healthcare providers administering this antipsychotic. The distinction between the short-acting formulation reconstituted with sterile water and the long-acting Zyprexa Relprevv formulation reconstituted with its specific supplied diluent is paramount to patient safety. Strict adherence to the correct reconstitution technique, administration site, and especially the mandatory 3-hour post-injection observation period for Zyprexa Relprevv, are essential to prevent medication errors and manage the risk of serious adverse events like PDSS.

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For more detailed information, consult the official prescribing information from the manufacturer or the FDA. A useful resource can be found at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022173s027lbl.pdf [1.4.3]

Frequently Asked Questions

What happens if I use the wrong liquid to dilute olanzapine injection?

Using the wrong diluent is dangerous. For short-acting olanzapine, using lorazepam injection causes delayed reconstitution, and diazepam causes precipitation [1.2.6, 1.4.5]. For long-acting Zyprexa Relprevv, only the manufacturer-supplied diluent can be used to ensure proper suspension and absorption [1.3.7].

How long is reconstituted olanzapine stable?

Reconstituted short-acting olanzapine injection should be used immediately, within one hour of mixing [1.2.2, 1.6.2]. Reconstituted Zyprexa Relprevv (long-acting) is stable in the vial for up to 24 hours at room temperature, but should be administered immediately after being drawn into a syringe [1.6.4].

Can you administer olanzapine injection intravenously?

No. Both the short-acting and long-acting formulations of olanzapine are intended for intramuscular (IM) use only. They must not be administered intravenously or subcutaneously [1.2.1, 1.4.5].

What is Post-injection Delirium/Sedation Syndrome (PDSS)?

PDSS is a rare but serious adverse event associated with the long-acting olanzapine injection (Zyprexa Relprevv). It involves symptoms of olanzapine overdose, like excessive sedation and delirium, that can occur if the medication accidentally enters the bloodstream [1.7.6]. This is why a 3-hour post-injection observation period is mandatory [1.4.3].

What should the final mixture look like?

For short-acting olanzapine, the final mixture should be a clear, yellow solution [1.2.2]. For long-acting olanzapine (Zyprexa Relprevv), it should be a smooth, yellow, and opaque suspension after vigorous shaking [1.3.6].

What is the proper administration site for olanzapine injection?

Short-acting olanzapine should be injected deep into a large muscle mass [1.2.1]. The long-acting Zyprexa Relprevv formulation has a stricter requirement and must only be injected deep into the gluteal muscle [1.3.7, 1.4.3].

Can you mix olanzapine in the same syringe with other drugs?

No, short-acting olanzapine for injection should not be combined in a syringe with diazepam or haloperidol injections, as this can cause precipitation or degradation of the olanzapine [1.2.6, 1.4.5]. Each medication should be prepared and administered separately.