FDA approves Weltruza, a once-monthly subcutaneous olanzapine with no observation period

For more than fifteen years, clinicians who wanted olanzapine in a long-acting form had one choice, and it came with a waiting room. Every injection of Zyprexa Relprevv (olanzapine pamoate) has to be followed by at least three hours of continuous observation in a certified setting. The reason is post-injection delirium/sedation syndrome, or PDSS. That requirement helps explain why olanzapine never became a widely used depot.

On October 9, 2026, Teva announced that the FDA had approved Weltruza (olanzapine extended-release injectable suspension). It is given once a month as a subcutaneous injection and has no observation requirement. The company said it expects US availability in the coming weeks. An application is also under review at the European Medicines Agency.

One product, several names

Weltruza is the olanzapine depot Teva and Medincell have presented at meetings for two years. Teva developed it as TEV-'749, submitted the NDA in December 2025, and the FDA accepted the application in February 2026. The drug uses Medincell's SteadyTeq copolymer technology. After subcutaneous injection, the polymer precipitates into a depot that releases olanzapine slowly. The same platform underlies Uzedy (subcutaneous risperidone), approved in 2023, so Weltruza is the second US approval from the Teva–Medincell partnership.

What SOLARIS showed

The approval rests on the phase 3 SOLARIS trial, which enrolled 675 adults aged 18 to 64 with schizophrenia. Its first period was an 8-week, randomized, double-blind, placebo-controlled comparison of three doses. An open-label safety extension of up to 48 weeks followed, giving up to 56 weeks of exposure in total.

• Efficacy: All three doses met the primary endpoint, which was change in PANSS total score at week 8 compared with placebo. In Teva's 2024 topline release, the placebo-adjusted reductions were roughly 10 to 11 points (adjusted p < 0.001 for each dose). CGI-S and Personal and Social Performance (PSP) scores also separated from placebo after multiplicity adjustment.
• PDSS: Teva reported no PDSS events through 56 weeks. At the time of the 2024 topline release, about 80% of the target number of injections had been given.
• Local and metabolic effects: Coverage of the long-term data reported injection-site induration and pain in 12% of participants each, erythema in 10% and pruritus in 7%. Weight gain was reported in 36%, and the overall systemic profile was described as consistent with oral olanzapine.

Most of these figures come from company releases and trade coverage of meeting presentations, not from a full peer-reviewed paper. The extension data are open-label.

How it compares with olanzapine pamoate

	Weltruza	Zyprexa Relprevv
Route	Subcutaneous (abdomen)	Deep intramuscular gluteal
Interval	Once monthly	Every 2 or 4 weeks
Doses	318, 425 or 531 mg, corresponding to oral 10, 15 or 20 mg/day	Dose set from the oral dose, with a higher initiation regimen
Post-injection observation	None required	At least 3 hours in a REMS-certified setting
PDSS on label	Warning: not known whether it can occur	Boxed warning

The Relprevv label puts the risk in context: PDSS occurred in under 0.1% of injections, which was about 2% of patients treated for up to 46 months. The episodes were serious, though. Symptoms ranged from confusion and slurred speech to coma, and many patients were hospitalized. Because of the REMS, the prescriber, the facility, the pharmacy and the patient all have to be enrolled.

The new label's wording on PDSS deserves attention. "Not known whether it can occur" means it has not been seen, not that it has been ruled out. A syndrome that appears in fewer than one in a thousand injections can easily go undetected in a single program of a few hundred patients.

What we still don't know

As of this writing we could not find a published list price or a date for first shipments. There are no head-to-head data against other monthly LAIs. Real-world PDSS surveillance will only begin once the drug is in wide use. Postmarketing experience will show whether the convenience holds up.