FDA Approves Once-Monthly Subcutaneous Olanzapine Injection for Schizophrenia

The FDA has granted approval for an easier-to-administer, once-monthly subcutaneous injectable form of olanzapine (Weltruza) for the treatment of schizophrenia in adults. Teva Pharmaceuticals announced the clearance on Friday.

While decades-old oral olanzapine remains the most widely prescribed atypical antipsychotic, daily treatment regimens often present adherence challenges. Consequently, some patients prefer less frequent dosing schedules.

The new long-acting injectable requires no loading doses and eliminates the need for monitoring post-injection delirium/sedation syndrome (PDSS). This addresses a significant barrier that has limited the adoption of other available long-acting olanzapine formulations, such as Zyprexa Relprevv, which carries a risk evaluation and mitigation strategy (REMS) program requiring three hours of post-injection monitoring for PDSS.

PDSS has been associated with agitation, anxiety, and confusion, with reports documenting patients stumbling into walls or falling asleep in public settings during the first few hours following treatment.

“Olanzapine has been a trusted and foundational treatment option for people living with schizophrenia for more than 30 years, but adherence continues to be a major barrier to stability, particularly for those who rely on daily oral medications,” said Christoph Correll, MD, of the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, in the company’s press release.

“By offering a subcutaneous long-acting injectable formulation with achievement of therapeutic blood levels without oral cotreatment, loading doses, or booster injections, this new treatment option can help empower patients, support their care partners, and provide clinicians with an important new tool to assist in managing this complex condition more effectively,” Correll added.

To correspond with the approved oral olanzapine doses of 10 mg, 15 mg, and 20 mg, the new long-acting injectable will be available in strengths of 318 mg, 425 mg, and 531 mg, respectively.

Approval was supported by the phase III SOLARIS trial. For the primary endpoint, all dose groups surpassed placebo regarding the mean difference in change in the Positive and Negative Syndrome Scale (PANSS) total score, according to a 2024 press release from Teva. From baseline to week 8, differences ranged from -9.71 to -11.27 points (P<0.001 for all comparisons). Other key secondary endpoints, including Clinical Global Impressions-schizophrenia and Personal and Social Performance Scale measures, also demonstrated superiority, and no PDSS cases were reported.

Like other antipsychotics, the new olanzapine product carries a boxed warning regarding an increased mortality risk for elderly patients with dementia-related psychosis.

Despite no evidence of PDSS in trials, the labeling for the new olanzapine product still lists PDSS among the warnings and precautions. Other potential risks noted in that section include neuroleptic malignant syndrome, metabolic changes, tardive dyskinesia, orthostatic hypotension, leukopenia, neutropenia, and agranulocytosis, seizures, potential for cognitive and motor impairment, anticholinergic effects, and laboratory abnormalities.

The safety profile in SOLARIS was generally consistent with oral olanzapine. Common adverse events included increased weight, somnolence, headache, and constipation, along with reactions specific to the injection formulation, such as induration, pain, erythema, pruritus, and swelling at the injection site.

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