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ZypAdhera ® (olanzapine pamoate monohydrate)
ZypAdhera® (olanzapine pamoate): Switching to Oral or to Other Antipsychotic Agents
If a switch to another antipsychotic medicinal product is intended, the slow dissolution of the olanzapine pamoate salt should be considered, especially during the first 2 months after discontinuation of olanzapine pamoate.
There are no systematically collected data to specifically address switching patients from olanzapine pamoate to other antipsychotic medicinal products.1
Due to the slow dissolution of the olanzapine pamoate salt, which provides a slow continuous release of olanzapine that is complete approximately six to eight months after the last injection, supervision by a clinician, especially during the first 2 months after discontinuation of olanzapine pamoate, is needed when switching to another antipsychotic product and is considered medically appropriate.1
To switch a patient to another antipsychotic agent after discontinuation of olanzapine LAI, the new antipsychotic medication or oral olanzapine may be started at the next regularly scheduled injection visit or when clinically indicated.2 The effective half-life of olanzapine LAI is approximately 30 days, meaning the amount of olanzapine absorbed from intramuscular tissues decreases by approximately 50% every 30 days after the last injection of olanzapine LAI.3,4
In a review of clinical perspectives with regard to olanzapine PKs, the authors stated the following: “Clinicians should remain aware that when [olanzapine] LAI treatment is discontinued, the olanzapine plasma concentrations will decrease only slowly, and the contribution of the previous [olanzapine] LAI treatment toward a patient’s pharmacotherapy should be considered when initiating a subsequent antipsychotic treatment and deciding its dosing. Similar to the gradual accumulation toward a steady state during initiation, olanzapine concentrations will slowly decrease after discontinuation and clinically relevant amounts of olanzapine may still be present even beyond a 2- to 3-month period. With very sensitive assay methods, a detectable amount of olanzapine in plasma may persist for more than 6 months after the last [olanzapine] LAI injection. Although the clinical impact of low residual amounts of olanzapine in a patient is unknown, this aspect is important to consider when initiating another regimen of antipsychotic treatment after the discontinuation of any long-acting injection.”4
If switching from olanzapine LAI to oral olanzapine, the initial dosage of oral olanzapine required may not be as high as that used before starting olanzapine LAI and the patient should be monitored for AEs.
The half-life of olanzapine after olanzapine pamoate is 30 days compared to 30 hours following oral administration.1
The combination of the release profile and the dosage regimen (intramuscular injection every two or four weeks) result in sustained olanzapine plasma concentrations. Plasma concentrations remain measurable for several months after each olanzapine pamoate injection.1
The release becomes diminishingly smaller within eight to twelve weeks.1
The absorption and elimination are complete approximately six to eight months after the last injection.1
3. Mitchell M, Kothare P, Bergstrom R, et al. Single- and multiple-dose pharmacokinetic, safety, and tolerability profiles of olanzapine long-acting injection: an open-label, multicenter, nonrandomized study in patients with schizophrenia. Clin Ther. 2013;35(12):1890-1908. http://dx.doi.org/10.1016/j.clinthera.2013.09.023
4. Heres S, Kraemer S, Bergstrom RF, Detke HC. Pharmacokinetics of olanzapine long-acting injection: the clinical perspective. Int Clin Psychopharmacol. 2014;29(6):299-312. http://dx.doi.org/10.1097/yic.0000000000000040
AE = adverse event
LAI = long-acting injection = olanzapine pamoate
PK = pharmacokinetics
Date of Last Review: May 01, 2019