Olanzapine and samidorphan

Pronunciation: oh-LAN-za-peen-and-SAM-i-DOR-fan
Generic name: olanzapine/samidorphan
Brand name: Lybalvi
Dosage form: oral tablet (5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, 20 mg/10 mg)
Drug class: Psychotherapeutic combinations

Medically reviewed by Carmen Pope, BPharm. Last updated on Jun 13, 2025.

What is olanzapine and samidorphan?

Olanzapine/samidorphan is used to treat schizophrenia or bipolar I disorder. It is a fixed-dose combination tablet taken once a day. The brand name of olanzapine/samidorphan is Lybalvi.

• Patients using opioids or undergoing acute opioid withdrawal should not take olanzapine/samidorphan.
• Olanzapine/samidorphan is not a controlled substance.
• The samidorphan component of this combination tablet helps to mitigate weight gain associated with olanzapine use.

Olanzapine/samidorphan gained FDA approval on May 28, 2021, under the brand name Lybalvi. There is no generic.

FDA approvals and indications 

Olanzapine/samidorphan is FDA approved in adults for:

• Schizophrenia
• The acute treatment of manic or mixed episodes of bipolar I disorder, either alone or in combination with lithium or valproate
• The maintenance treatment of bipolar I disorder. 

It is not known if this medicine is safe or effective in children.

How does olanzapine/samidorphan work?

Olanzapine/samidorphan combines an antipsychotic (olanzapine) with an opioid antagonist (samidorphan). Each has a different mechanism of action.

• The exact mechanism for olanzapine is unknown but is thought to involve multiple neurotransmitter systems in the brain, primarily dopamine and serotonin. Olanzapine helps to manage symptoms such as hallucinations, delusions, and disorganized thinking, and belongs to the drug class called atypical antipsychotics.
• Samidorphan helps stop weight gain associated with olanzapine use by blocking opioid receptors in the brain and gut, counteracting some of the metabolic effects of olanzapine, particularly its tendency to increase appetite. It belongs to the drug class called opioid antagonists.

Side effects

In people with schizophrenia, the most common side effects of olanzapine/samidorphan are:

• weight gain
• sleepiness
• dry mouth
• headache.

In people with bipolar I disorder, the most common side effects of olanzapine/samidorphan are:

• weakness
• dry mouth
• constipation
• increased appetite
• sleepiness
• dizziness
• shaking.

Additional common side effects when used in combination with lithium or valproic acid are:

• back pain
• problems speaking
• mouth-watering
• memory problems
• numbness and tingling in your arms and legs.

Serious side effects and warnings

Olanzapine/samidorphan may cause the following serious side effects:

• Increased risk of death in elderly people. There is a Boxed Warning for an increased risk of death in elderly people with dementia-related psychosis. Olanzapine/samidorphan is not approved for the treatment of people with dementia-related psychosis.
• Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death. Olanzapine/samidorphan is not approved for the treatment of people with dementia-related psychosis.
• Opioid withdrawal. Do not take olanzapine and samidorphan for at least 7 days after you stop taking short-acting opioids and for at least 14 days after you stop taking long-acting opioids. One of the medicines in olanzapine and samidorphan (samidorphan) can cause opioid withdrawal that may be severe and cause hospitalization in people who are physically dependent on opioids. Talk to your healthcare provider if you have questions about the type of opioid you take.
• Risk of life-threatening opioid overdose. You should not start taking opioids for at least 5 days after you stop treatment with olanzapine and samidorphan. One of the medicines, samidorphan, can increase your chance of having an opioid overdose that can cause death if you take opioids during treatment or within 5 days after stopping treatment with olanzapine and samidorphan. You can accidentally overdose in 2 ways:
  • Because olanzapine/samidorphan blocks the effects of opioids, such as heroin, methadone, or opioid pain medicines, it may be tempting for some people to take large amounts of opioids to try to overcome these opioid-blocking effects. This can lead to serious injury, coma, or death.
  • The blocking effect of olanzapine/samidorphan slowly decreases and completely goes away over time. This may make you more sensitive to opioids. Using opioids in amounts that you may have used in the past can lead to overdose or death. Tell your family and the people closest to you of this increased sensitivity to opioids and the risk of overdose. You or someone close to you should get emergency medical help right away if you have trouble breathing, become very drowsy with slowed breathing, have slow, shallow breathing (little chest movement with breathing), or feel faint, very dizzy, confused, or have unusual symptoms.
• Neuroleptic malignant syndrome (NMS), is a serious condition that can lead to death. Call your healthcare provider or go to the nearest hospital emergency room right away if you have some or all of the following signs and symptoms of NMS:
  • high fever
  • sweating
  • stiff muscles
  • changes in your breathing, pulse, heart rate, and blood pressure
  • confusion.
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): One of the medicines in olanzapine and samidorphan (olanzapine) can cause DRESS which can cause death. Tell your healthcare provider right away if you develop any of the following symptoms of DRESS, including:
  • rash
  • fever
  • swollen glands
  • kidney problems
  • liver problems
  • lung problems
  • heart problems.
• High blood sugar (hyperglycemia) and diabetes. Clinical trials have shown blood sugar increases in some people who take olanzapine and samidorphan. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before you start and regularly during treatment with olanzapine and samidorphan. Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with olanzapine and samidorphan:
  • 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 should check the fat levels in your blood before you start and regularly during treatment with olanzapine and samidorphan.
• Weight gain. You and your healthcare provider should check your weight before you start and often during treatment with olanzapine/samidorphan.
• Uncontrolled body movements (tardive dyskinesia). Olanzapine/samidorphan may cause movements you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking this medicine. Tardive dyskinesia may also start after you stop taking this medicine.
• Decreased blood pressure (orthostatic hypotension) and fainting. You may feel lightheaded or faint when you rise too quickly from a sitting or lying position.
• Falls. Olanzapine/samidorphan may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position (orthostatic hypotension), and slow your thinking and motor skills, leading to falls that can cause fractures or other injuries.
• Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment with olanzapine/samidorphan.
• Difficulty swallowing that can cause food or liquid to get into your lungs.
• Seizures (convulsions).
• Problems controlling your body temperature so that you feel too warm. 
• Increased prolactin levels in your blood. Your healthcare provider may do blood tests to check your prolactin levels during treatment with olanzapine and samidorphan.

It is not known if this medicine is safe or effective in children.

Tell your healthcare provider that you are taking olanzapine/samidorphan before any medical procedure or surgery.

These are not all the possible side effects of olanzapine and samidorphan. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA1088.

Related/similar drugs

False positives on opioid screening tests

Tell your healthcare provider if you take a urine drug screening test because olanzapine/samidorphan may cause false-positive results in opioid urine screening tests.

If you do experience a positive result for an opioid urine drug screening test and you take this medicine, ask the testing provider to use a different analytical technique, such as chromatography, to confirm or negate positive results.

Before taking

Do not take olanzapine and samidorphan if you are taking opioids or are experiencing acute opioid withdrawal.

Before taking olanzapine and samidorphan, tell your healthcare provider about all of your medical conditions, including if you:

• have or had heart problems or a stroke
• use or abuse street drugs (illegal substances)
• have or had low or high blood pressure
• have kidney problems
• have diabetes or high blood sugar, or a family history of diabetes or high blood sugar
• have or have had high levels of total cholesterol, LDL cholesterol, or triglycerides, or low levels of HDL cholesterol
• have or had a low white blood cell count
• have problems swallowing
• have or had seizures (convulsions)
• have or had problems with urination or prostate problems
• have or had breast cancer
• have or had constipation or a bowel obstruction
• have or had high prolactin levels
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

Talk to your healthcare provider about the risks to you and your unborn or newborn baby if you take olanzapine and samidorphan during pregnancy.

Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with olanzapine and samidorphan.

If you become pregnant during treatment with olanzapine and samidorphan, 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 by visiting http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/

Breastfeeding

Olanzapine/samidorphan can pass into breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment.

How do I take olanzapine/samidorphan?

Take this medicine exactly as your healthcare provider tells you to take it. Do not change the dose or stop taking olanzapine/samidorphan without first talking to your healthcare provider.

• Take once a day.
• Take with or without food.
• Swallow the tablets whole.
• Do not split or combine different-strength olanzapine/samidorphan tablets.

Dosing information

Dose of olanzapine/samidorphan for schizophrenia:

• Initial dose: 5 mg/10 mg or 10 mg/10 mg
• Maintenance dosage: 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg

Dose of olanzapine/samidorphan for Bipolar I disorder (alone)

• Initial dose: 10 mg/10 mg or 15 mg/10 mg
• Maintenance dosage: 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg

Dose of olanzapine/samidorphan for Bipolar I disorder with lithium or valproate

• Initial dose: 10 mg/10 mg 
• Maintenance dosage: 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg

What happens if I overdose?

If you take too much olanzapine and samidorphan, call your Poison Control Center at 1-800-222-1222 or go to the nearest hospital emergency room right away.

What should I avoid while taking olanzapine and samidorphan?

Olanzapine/samidorphan can make you feel sleepy. Do not drive a car, operate machinery, or do other dangerous activities until you know how this medicine affects you.

Do not drink alcohol with olanzapine/samidorphan.

Avoid getting overheated or dehydrated.

• 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.

What other drugs will affect this medicine?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Olanzapine/samidorphan may affect the way some other medicines work. Other medicines may affect the way it works. Especially tell your healthcare provider if you:

• take opioids or have stopped taking opioids in the past 14 days
• take or plan to take other olanzapine-containing medicines.

Do not start or stop any medicines while taking olanzapine/samidorphan without first talking to your healthcare provider. Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine

Storage

Store at room temperature in the original container. Keep tightly closed, in a dry place, and away from moisture.

Keep out of the reach of children.

Ingredients

Olanzapine/samidorphan is only available as Lybalvi.

Active ingredients: olanzapine, samidorphan.

Inactive ingredients: colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium stearate, and microcrystalline cellulose.

Film coating ingredients include hypromellose, titanium dioxide, triacetin, and iron oxide yellow (5 mg/10 mg); iron oxide yellow and iron oxide red (10 mg/10 mg); FD&C Blue No. 2/indigo carmine aluminum lake (15 mg/10 mg); iron oxide red (20 mg/10 mg).

Available in the following tablet strengths:

• 5 mg/10 mg
• 10 mg/10 mg
• 15 mg/10 mg
• 20 mg/10 mg.

Manufacturer

Olanzapine/samidorphan combination tablets are made by Alkermes, Inc., under the brand Lyblavi. Their headquarters are in Dublin, Ireland, and they have a research center in Waltham, Massachusetts, and a manufacturing facility in Wilmington, Ohio.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer