Olanzapine Long-Acting Injection

Abstract

Olanzapine pamoate (olanzapine long-acting injection [OLAI]; Zypadhera®; Zyprexa® Relprevv™) is the intramuscular depot formulation of the atypical antipsychotic olanzapine. In two pivotal, double-blind clinical trials of 8 or 24 weeks' duration, the efficacy of recommended dosages of OLAI injected every 2 or 4 weeks (without oral supplementation) was greater than that of placebo in improving symptoms in acutely ill patients with schizophrenia, and generally similar to that of continuing oral olanzapine in preventing psychotic exacerbations in patients with schizophrenia whose symptoms had previously been stabilized on oral olanzapine. The effectiveness of OLAI in the maintenance treatment of schizophrenia was also demonstrated in an (ongoing) open-label extension study in which the all-cause discontinuation rate was 34.3% after 18 months. OLAI is generally well tolerated. It has an adverse event profile similar to that of oral olanzapine, with the exception of adverse events related to the intramuscular route of administration; these include a manageable post-injection syndrome, which occurred in <0.1% of injections in clinical trials. The possibility of a post-injection syndrome event requires a risk management plan (RMP) to be adopted that includes observation by appropriately qualified personnel in a healthcare facility for at least 3 hours post-injection. With its potential to improve adherence to medication, and thereby treatment outcomes, OLAI is a useful addition to the pharmacological options available for the maintenance therapy of schizophrenia. Given its benefit/risk profile, OLAI appears most suited for patients who, despite responding well to oral olanzapine, have difficulties remaining adherent to this form of medication, provided they can comply with the conditions of the RMP.

Long-Acting Atypical Antipsychotics: Characterization of the Local Tissue Response

“…Nevertheless, redness, pain, swelling, and nodule formation at the site of injection have been reported with both these compounds (3, 23–26). The LAI formulation of olanzapine pamoate monohydrate (Zyprexa Relprevv®) has an incidence of injection site reactions of 8.4%, similar to what was reported with haloperidol (4, 27, 28) . Aripiprazole monohydrate (Abilify® Maintena™), recently approved by the U.S. Food and Drug Administration (FDA)-as an extended release formulation, has a reported injection site-related adverse events of 6.3%, with investigator evaluation noting injections site pain, redness, swelling, and induration in 4–26% of subjects in open label stabilization phase studies (38) , (29).…”

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

“…OLZ selectively reduces the activity of dopaminergic mesolimbic (A10) neurons but not dopaminergic striatal (A9) neuron fire and, in animal studies, counteracts conditioned avoidance behavior (test of antipsychotic efficacy) at a dose that is not sufficient to induce catalepsy (test of motor side effect) (Chiodo and Bunney, 1983[25]; Stockton and Rasmussen, 1996[142]; Frampton, 2010[51]). More recently, preclinical studies have shown that OLZ efficacy on psychotic and cognitive symptoms of schizophrenia may be represented by its facilitating effect on N-methyl-D-aspartic acid, which can favor brain derived neurotrophic factor (BDNF) expression (Horacek et al, 2006[67]).…”

Efficacy of olanzapine long-acting injection in patients with acutely exacerbated schizophrenia: an insight from effect size comparison with historical oral data

“…Olanzapine long-acting injection (LAI) has demonstrated efficacy in acutely ill patients [9] and has demonstrated similarity to oral olanzapine in terms of maintenance of effect and safety during longer-term treatment [10]; several recent reviews are available [11-13]. However, no direct comparisons of oral and LAI olanzapine have been done within the acute phase of treatment.…”