FDA Approves First Once-Monthly Subcutaneous Olanzapine LAI for Adults With Schizophrenia

The FDA approved olanzapine for extended-release injectable suspension (Weltruza; Teva Pharmaceuticals), the first once-monthly subcutaneous long-acting injectable (LAI) formulation of olanzapine, for the treatment of schizophrenia in adults. According to Teva Pharmaceuticals’ announcement, the treatment requires no loading doses, no oral supplementation, and no postinjection monitoring.¹

The LAI will be available in once-monthly doses of 318 mg, 425 mg, and 531 mg, which correspond to daily oral olanzapine doses of 10 mg, 15 mg, and 20 mg, respectively. Teva notes that the product is expected to be available in the US in the coming weeks.¹

Closing the Gap Between Oral and Injectable Olanzapine

Adherence remains a central challenge in schizophrenia, with an estimated half of patients exhibiting nonadherence, and the American Psychiatric Association recommends considering LAI antipsychotics for patients with poor or unknown adherence.² Although olanzapine is among the more efficacious antipsychotics available, its existing intramuscular LAI formulation, olanzapine pamoate (Zyprexa Relprevv; Eli Lilly), has seen limited use. Approximately 19% of patients taking oral antipsychotics for schizophrenia use olanzapine, compared with fewer than 0.1% of patients on an LAI who use the intramuscular formulation.²

That gap is largely attributable to postinjection delirium/sedation syndrome (PDSS), which occurs in an estimated 1.4% of patients and presents as sedation, delirium, or extrapyramidal symptoms after injection. The intramuscular product is restricted under a Risk Evaluation and Mitigation Strategy program requiring at least 3 hours of patient observation at a certified facility after each injection.²

Weltruza uses SteadyTeq, a copolymer drug delivery technology developed by MedinCell and licensed to Teva. After subcutaneous injection, the copolymer precipitates to form a depot that releases olanzapine in a controlled, sustained manner, avoiding the uncontrolled dissolution seen with the pamoate salt. Subcutaneous administration also lowers the risk of inadvertent intravascular access, which has been associated with PDSS.²

Christoph Correll, MD, coordinating investigator of the SOLARIS trial and professor of psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, noted in the announcement that olanzapine has been a foundational therapy for decades but that adherence to daily oral medication remains a major barrier to stability. He added that reaching therapeutic blood levels without oral cotreatment, loading doses, or booster injections could support patients, their care partners, and health care professionals.¹

SOLARIS Efficacy Results

The approval was based on the phase 3 SOLARIS trial (NCT05693935)³, a multinational, randomized, double-blind, placebo-controlled study that enrolled 675 adults aged 18 to 64 years with schizophrenia. During an 8-week acute treatment period, participants were randomly assigned to once-monthly subcutaneous olanzapine at 318 mg, 425 mg, or 531 mg, or to placebo. Participants could then enter an open-label safety period of up to 48 weeks, during which those initially receiving placebo were randomly assigned to 1 of the 3 active doses.^2,3

All 3 doses met the primary end point of change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 8. Placebo-adjusted differences were about −9.71 points for the 318-mg dose, −11.27 points for the 425-mg dose, and −9.71 points for the 531-mg dose (adjusted P < .001 for each).⁴ Patients receiving active treatment also showed significant improvements in Clinical Global Impression–Severity (CGI-S) and Personal and Social Performance scale scores vs placebo.^1,2

In the open-label period, effectiveness was maintained across all doses, with stable mean changes from period 2 baseline of −7.2 in PANSS total score and −0.5 in CGI-S score.^5,6

Safety and Tolerability

In an integrated long-term safety analysis through week 56, no suspected or confirmed PDSS events were reported across 3470 subcutaneous injections, and the systemic safety profile was consistent with second-generation antipsychotic class effects and other olanzapine formulations.⁶ However, the prescribing information notes that PDSS has occurred with intramuscular extended-release olanzapine and that it is not known whether it can occur with the LAI.¹

In the long-term analysis, increased weight was reported in 36% of participants. Injection site induration and pain each occurred in 12% of participants, erythema in 10%, and pruritus and somnolence in 7% each. Among 137 participants treated for at least 48 weeks, mean weight gain from baseline was 5.6 kg, which was consistent with long-term data for oral olanzapine.^2,6 Headache and constipation were also among the commonly reported adverse events.¹

As with other antipsychotics, the formulation carries a boxed warning for increased mortality in older adults with dementia-related psychosis and is not approved for that population.¹

Implications for Pharmacists

For patients who respond to oral olanzapine but struggle with daily adherence, the newly approved LAI offers a once-monthly option with a straightforward conversion from established oral doses. Removing the 3-hour postinjection observation requirement may also ease workflow burdens in clinics, health systems, and other settings that administer LAIs.

The new formulation does not change olanzapine’s metabolic profile. Pharmacists should still continue to counsel patients on weight gain and support baseline and ongoing monitoring of weight, glucose, and lipids, along with education on injection site reactions and sedation.

“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,” Christoph Correll, MD, clinical professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, said in the news release. “By offering a subcutaneous LAI 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.”¹

REFERENCES

1. Teva announces U.S. Food and Drug Administration (FDA) approval of Weltruza (olanzapine) for extended-release injectable suspension, as the first and only once-monthly subcutaneous injectable olanzapine for adults with schizophrenia. News release. Teva Pharmaceuticals. October 9, 2026. Accessed October 12, 2026. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2026/Teva-Announces-U-S--Food-and-Drug-Administration-FDA-Approval-of-WELTRUZA-Olanzapine-For-Extended-Release-Injectable-Suspension-as-the-First-and-Only-Once-Monthly-Subcutaneous-Injectable-Olanzapine-for-Adults-with-Schizophrenia/default.aspx

2. Olivas M, Tran TT. Subcutaneous olanzapine in schizophrenia: expanding the utility of a proven therapy. Pharmacy Times. July 15, 2026. Accessed October 12, 2026. https://www.pharmacytimes.com/view/subcutaneous-olanzapine-in-schizophrenia-expanding-the-utility-of-a-proven-therapy

3. A study to test if TV-44749 is effective in relieving schizophrenia (SOLARIS). ClinicalTrials.gov identifier: NCT05693935. Updated March 17, 2026. Accessed October 12, 2026. https://clinicaltrials.gov/study/NCT05693935

4. Teva and Medincell announce positive phase 3 efficacy results from SOLARIS trial evaluating TEV-'749 (olanzapine) as a once-monthly subcutaneous long-acting injectable in adults with schizophrenia. News release. Teva Pharmaceuticals. May 8, 2024. Accessed October 12, 2026. https://www.tevausa.com/news-and-media/press-releases/teva-and-medincell-announce-positive-phase-3-efficacy-results-from-solaris-trial-evaluating-tev-749-ola/

5. Perlstein I, Cherniakov I, Elgart A, et al. Population Pharmacokinetic Model-Based Dose Selection of Extended-Release Injectable Olanzapine (TV-44749) for Subcutaneous Use in Phase 3 Clinical Trial in Adults with Schizophrenia. J Clin Pharmacol. 2026;66(1):e70144. doi:10.1002/jcph.70144

6. New long-term safety data from the completed phase 3 SOLARIS trial support the potential of olanzapine LAI (TEV-'749) as the first long-acting olanzapine treatment option for schizophrenia with no PDSS observed. News release. Teva Pharmaceuticals. September 21, 2025. Accessed October 12, 2026. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2025/New-Long-term-Safety-Data-from-the-Completed-Phase-3-SOLARIS-Trial-Support-the-Potential-of-Olanzapine-LAI-TEV-749-as-the-First-Long-Acting-Olanzapine-Treatment-Option-for-Schizophrenia-with-No-PDSS-