Weltruza

Weltruza is used to treat schizophrenia in adults. It is a long-acting, subcutaneous (under the skin) formulation of olanzapine, given by a healthcare provider once a month.

The way Weltruza (olanzapine) works in schizophrenia is unclear, but its effects are thought to come from blocking dopamine and serotonin type 2 (5HT2) receptors in the brain. Olanzapine also attaches to several other receptors:

• Strongly: serotonin (5HT2A/2C, 5HT6), dopamine (D1 to D4), histamine (H1), and adrenergic alpha-1 receptors.
• Moderately, as a blocker: serotonin 5HT3 and muscarinic (M1 to M5) receptors.

Weltruza belongs to the drug class called atypical antipsychotics.

Weltruza (olanzapine) received FDA approval on October 8, 2026. There is no generic Weltruza.

Weltruza carries a Boxed Warning for an increased risk of death in elderly people with dementia-related psychosis.

Increased risk of death in elderly people with dementia-related psychosis

Weltruza increases the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Weltruza is not for the treatment of people with dementia-related psychosis.

See "What are the possible side effects of Weltruza?" for more information about side effects.

Before receiving Weltruza, tell your healthcare provider about all of your medical conditions, including if you:

• have or had diabetes or high blood sugar
• have or had high levels of total cholesterol, LDL cholesterol, or triglycerides, or low HDL levels in your blood
• have or had low or high blood pressure
• have or had heart problems or stroke
• are dehydrated
• have or had a low white blood cell count
• have or had seizures (convulsions)
• have or had problems with urination or prostate problems
• have Alzheimer's disease
• have or had constipation or bowel obstruction
• have or had breast cancer
• are pregnant or plan to become pregnant. Weltruza may harm your unborn baby. Receiving Weltruza during your third trimester of pregnancy may cause your baby to have abnormal muscle movements or withdrawal symptoms such as agitation, stiffness or floppiness, tremors, sleepiness, and breathing or feeding problems after birth. Talk to your healthcare provider about the risks to your baby if you receive Weltruza during pregnancy. If you become pregnant during treatment with Weltruza, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or go to http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
• are breastfeeding or plan to breastfeed. Weltruza passes into breast milk. If you breastfeed during treatment with Weltruza, tell your healthcare provider if your baby is very sleepy, irritable, is feeding poorly, or gets tremors or abnormal muscle movements. Talk to your healthcare provider about the best way to feed your baby during treatment with Weltruza.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter, vitamins, and herbal supplements.

It is not known if Weltruza is safe and effective in children.

Serious side effects

Weltruza can cause serious side effects, including:

• See "What is the most important information I should know about Weltruza?"
• Post-injection delirium/sedation syndrome (PDSS). PDSS is a serious problem that can happen when too much olanzapine enters the bloodstream too quickly. PDSS has happened in people who received another extended-release olanzapine medicine by injection into their muscles (intramuscularly). Weltruza is injected under the skin (subcutaneously). It is not known whether PDSS can happen with Weltruza. PDSS with an extended-release intramuscular injection has led to hospitalization, has happened within the first 3 hours of injection, but also happened after 3 hours of injection, and has the risk each time an injection is received. Tell your healthcare provider right away or go to the nearest emergency room if you get signs or symptoms of PDSS, including: feeling more sleepy than usual feeling grouchy or angry dizziness feeling anxious or nervous confusion or disorientation increased blood pressure trouble walking or talking seizures (convulsions) stiff muscles or shakiness passing out (loss of consciousness) weakness
• Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death.
• Neuroleptic Malignant Syndrome (NMS), a serious condition that can lead to death: Tell your healthcare provider right away or go to the nearest emergency room if you get any signs or symptoms of NMS, including: high fever changes in pulse, heart rate, or blood pressure stiff muscles increased sweating confusion
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). DRESS is an allergic reaction that can cause death and may affect your skin or other parts of your body, including your liver, kidneys, lungs, or heart. Tell your healthcare provider right away if you get any signs or symptoms of DRESS, including: fever chest pain skin rash or blistering or peeling skin yellowing of the skin or the white parts of your eyes swelling of the face, glands, or other parts of the body dark urine or changes in urination cough or trouble breathing
• Problems with your metabolism such as: high blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who are treated with Weltruza. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before you start and during treatment with Weltruza. If you have diabetes or high blood sugar, you should follow your healthcare provider's instructions about how often to check your blood sugar during treatment with Weltruza. Tell your healthcare provider if you have any of these symptoms of high blood sugar while receiving Weltruza: feel very thirsty need to urinate more than usual feel very hungry feel weak or tired feel sick to your stomach feel confused, or your breath smells fruity increased fat levels (cholesterol and triglycerides) in your blood. Your healthcare provider may check your cholesterol and triglyceride levels during treatment with Weltruza. weight gain. You and your healthcare provider should check your weight regularly during treatment with Weltruza.
• Uncontrolled body movements (Tardive dyskinesia [TD]) in your face, tongue or other body parts. TD may not go away, even if you stop receiving Weltruza. TD may also start after you stop receiving Weltruza. Tell your healthcare provider if you get any body movements that you cannot control.
• Decreased blood pressure (orthostatic hypotension). You may feel dizzy or lightheaded, get a fast or slow heartbeat, or faint, when you rise too quickly from a sitting or lying position. Drinking alcohol and using other medicines that make you dizzy can increase your risk for orthostatic hypotension.
• Falls. Weltruza may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position (orthostatic hypotension), and can slow your thinking and motor skills which may lead to falls that can cause fractures or other injuries.
• Low white blood cell counts. Your healthcare provider may do white blood cell count tests during your first few months of treatment with Weltruza.
• Difficulty swallowing, which can cause food or liquid to get into your lungs.
• Seizures (convulsions).
• Sleepiness, drowsiness, feeling tired, difficulty thinking and doing normal activities. See "What should I avoid while receiving Weltruza?"
• Problems controlling your body temperature so that you feel too warm. See "What should I avoid while receiving Weltruza?"
• Certain side effects from the way Weltruza works in your body, such as constipation, dry mouth, fast heartbeat, urinary retention, or prostate and bowel problems. Your risk is increased if you take other medicines that also cause these side effects.
• Increased prolactin levels in your blood (hyperprolactinemia). Weltruza can cause a rise in the blood levels of a hormone called prolactin that may cause side effects including missed menstrual periods, a reversible reduction in fertility in females who can become pregnant, leakage of milk from the breasts, development of breasts in men, or problems with erection.

Common side effects

The most common side effects of Weltruza include:

• weight gain
• constipation
• sleepiness
• injection site reactions including hardness, pain, redness, itching, and swelling
• headache

These are not all of the possible side effects of Weltruza. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In an 8-week trial (NCT05693935), adults with an acute worsening of schizophrenia received 2 monthly injections of Weltruza 318 mg, 425 mg, or 531 mg, or placebo.

• PANSS total symptom scores (range 30 to 210) fell by 21.9 to 23.4 points with Weltruza, compared with 12.2 points with placebo.
• Improvement over placebo was 9.8 points (318 mg), 11.3 points (425 mg), and 9.8 points (531 mg).
• Illness severity (CGI-S) and social functioning (PSP) scores also improved significantly versus placebo.
• Improvements were sustained through 48 weeks in the open-label extension.

• Follow your treatment schedule exactly as your healthcare provider tells you to.
• Weltruza is injected by your healthcare provider under the skin (subcutaneously) in your stomach (abdomen).
• You should receive Weltruza 1 time every month.
• If you miss an injection of Weltruza, call your healthcare provider right away to reschedule your appointment so you can receive your next injection as soon as possible.
• Call your healthcare provider if you do not think you are getting better or have any concerns about your condition.

• Do not drive, operate heavy machinery, or do other dangerous activities until you know how Weltruza affects you. Weltruza may affect your judgement, thinking, or motor skills.
• Avoid drinking alcohol during treatment with Weltruza. Drinking alcohol increases your risks of getting dizziness, sleepiness, and other side effects from Weltruza.
• Avoid getting too hot or dehydrated during treatment with Weltruza. Do not exercise too much. In hot weather, stay inside in a cool place if possible. Stay out of the sun. Do not wear too much clothing or heavy clothing. Drink plenty of water.

Weltruza and some medicines may affect each other and may not work as well or may cause possible serious side effects. Your healthcare provider can tell you if it is safe to receive Weltruza with your other medicines.

Especially tell your healthcare provider if you take:

• blood pressure medicines (anti-hypertensives)
• levodopa or dopamine agonists
• medicines with anticholinergic effects, which can increase the risk of severe constipation and bowel problems
• carbamazepine, rifampin, or other medicines that can lower olanzapine levels
• fluvoxamine or other medicines that can raise olanzapine levels
• other medicines that contain olanzapine.

Using Weltruza with alcohol or other medicines that act on the brain (centrally acting drugs) can increase the risk of dizziness, lightheadedness, or fainting when you stand up (orthostatic hypotension).

This list is not complete. Other drugs may interact with olanzapine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here. Do not start or stop any medicines during treatment with Weltruza without talking to your healthcare provider first.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Active ingredient: olanzapine

Inactive ingredients: poly(ethylene glycol)-co-poly (D, L-lactide) copolymers and dimethyl sulfoxide.