Why does Lybalvi have a boxed warning?

This medication has a boxed warning, the highest safety-related warning assigned by the FDA to a drug label. The boxed warning states that Lybalvi increases the risk of death in older people with confusion and memory loss (dementia). Therefore, it is not approved for treating dementia-related psychosis.

What drugs should not be taken with Lybalvi?

You should not start Lybalvi for at least one to two weeks after stopping opioid treatment, depending on whether you were taking short- or long-acting opioids. Do not use opioids while you are on Lybalvi. Lybalvi may also interact with the following types of medications: · Strong CYP3A4 inducers · Strong CYP1A2 inhibitors · CYP1A2 inducers · Diazepam, alcohol, or drugs that affect the central nervous system · Anticholinergic drugs · Antihypertensive agents · Levodopa and dopamine agonists Talk to your healthcare provider or pharmacist for more detailed information on drug interactions.

Will I gain weight on Lybalvi?

Studies have shown that Lybalvi causes less weight gain and a smaller increase in waist circumference compared with olanzapine alone. However, weight gain is still the most common adverse event with this drug. You should monitor your weight before and during Lybalvi. Samidorphan appears to reduce olanzapine-induced weight gain.

Lybalvi (Olanzapine and Samidorphan) Oral: Uses, Side Effects, Dosages

Warning:

Lybalvi raises the risk of death in older individuals (aged 65 and above) with psychosis due to dementia. For this reason, it is not approved for treating dementia-related psychosis.

…

What Is Lybalvi?

Lybalvi is a combination prescription medication that contains two medicines (olanzapine and samidorphan).

Olanzapine is an atypical antipsychotic, while samidorphan is an opioid antagonist. Olanzapine blocks the activity of two naturally occurring brain chemicals: dopamine and serotonin. Samidorphan blocks opioid receptors with some agonist (binding) activity at kappa- and delta-opioid receptors.

Lybalvi is used only in adults to treat:

Schizophrenia
Short-term mixed/manic episodes of bipolar I disorder (alone or in combination with medications like lithium or valproate)
Mixed/manic episodes that happen with bipolar I disorder long-term

Lybalvi is not to be used in individuals with dementia-related psychosis, as it increases their risk of death.

This medication is available by prescription only. It comes in tablet form, which is taken by mouth.

Drug Facts

Generic Name: Olanzapine and samidorphan

Brand Name(s): Lybalvi

Drug Availability: Prescription

Administration Route: Oral

Therapeutic Classification: Atypical antipsychotic and opioid antagonist

Available Generically: No

Controlled Substance: N/A

Active Ingredient: Olanzapine and samidorphan L-malate

Dosage Form(s): Tablet

What Is Lybalvi Used For?

Lybalvi is used in adults for the treatment of:

Schizophrenia
Bipolar I disorder, for the acute treatment of manic or mixed episodes as an adjunct (add-on therapy), as monotherapy (single-therapy), or as maintenance monotherapy treatment

How to Take Lybalvi

Take your medication exactly as prescribed by your healthcare provider.

Take Lybalvi by mouth once daily, with or without food. Swallow the tablets whole. Do not split or crush them. Do not mix different strengths of the dosages. Your healthcare provider may start you on a low dose and gradually increase it.

Contact your healthcare provider before changing the dose or stopping Lybalvi.

Storage

Store Lybzalvi in its original bottle at room temperature (between 68 F and 77 F). Keep in a dry place with the bottle tightly closed. Leave the desiccant pack in the bottle to protect it from moisture. Keep away and out of reach from children and pets to prevent accidental consumption.

How Long Does Lybalvi Take to Work?

Lybalvi may start working in the body as soon as you start treatment, but you may not notice improvements for several weeks. In clinical trials, treatment with olanzapine and samidorphan significantly improved schizophrenia symptoms compared with placebo (inactive sugar pill) at four weeks after starting it. In another study, treatment ofolanzapine and samidorphan showed similar improvements at 24 weeks.

What Are the Side Effects of Lybalvi?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your pharmacist or a healthcare provider. You may report side effects to the Food and Drug Administration (FDA) at www.fda.gov/medwatch or 800-FDA-1088.

Common Side Effects

You may experience some side effects with Lybalvi. Common side effects reported with this medication include:

Weight gain
Drowsiness
Dry mouth
Increased appetite
Headache
Dizziness
Constipation
Back pain
Speech disturbance
Tremor
Upset stomach
Increased saliva
Memory loss
Tingling or prickling sensation (paresthesia)
Restlessness
Fatigue or lack of energy
Nausea
Impaired body temperature regulation

Severe Side Effects

Lybalvi has a boxed warning, the strictest safety-related warning assigned by the FDA for a medication. Older adults (65 years and older) with dementia-related psychosis associated with the use of antipsychotic drugs are at an increased risk for death. Lybalvi should not be prescribed for use in this population.

Other potentially severe side effects are possible with this medication. Notify your healthcare provider immediately if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

High prolactin levels in the blood (hyperprolactinemia), which can cause symptoms like irregular menstrual periods and erectile dysfunction
Neuroleptic malignant syndrome, which can cause hyperpyrexia (high fever), tremor, muscle cramps, and delirium
Tardive dyskinesia, resulting in uncontrolled movement(s)
High blood sugar or insulin and diabetes, which can cause extreme thirst or hunger, nausea, frequent urination, weakness or tiredness, or fruity-smelling breath
Diabetic ketoacidosis, a potentially life-threatening complication of diabetes
Abnormal lipid levels (dyslipidemia)
Severely low blood pressure, which can cause you to feel lightheaded or faint when you stand up too quickly from sitting or lying down
Fainting (syncope)
Severe difficulty swallowing, which can lead to choking
Impaired body temperature regulation, which can cause overheating
Severe allergic reaction, which can cause angioedema (swelling under the skin), hives, or anaphylactic reactions
Seizures, or convulsions

Priapism (an erection that persists for hours without sexual stimulation)
Abnormal liver function tests
Inflammation of the pancreas
Increased opioid sensitivity

Lybalvi may also affect blood cell counts, including:

Low neutrophil (neutropenia)
Low granulocyte count (agranulocytosis)
Low leukocyte count (leukopenia)

Based on your medical history, your healthcare provider may monitor your white blood cell count. Sometimes, stopping treatment with Lybalvi is necessary if white blood cell counts drop too low.

Long-Term Side Effects

Tardive dyskinesia, characterized by involuntary movements, may start or continue even after stopping treatment.

Report Side Effects

Lybalvi may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your healthcare provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

(800) 332-1088

Dosage: How Much Lybalvi Should I Take?

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage forms (tablets):
- For treatment of schizophrenia:
  - Adults—At first, 5 to 10 milligrams (mg) olanzapine and 10 mg samidorphan once a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 20 mg olanzapine and 10 mg samidorphan per day.
  - Children—Use and dose must be determined by your doctor.
- For treatment of mania or mixed episodes with bipolar disorder (olanzapine/samidorphan alone):
  - Adults—At first, 10 to 15 milligrams (mg) olanzapine and 10 mg samidorphan once a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 20 mg olanzapine and 10 mg samidorphan per day.
  - Children---Use and dose must be determined by your doctor.
- For treatment of mania or mixed episodes with bipolar disorder (olanzapine/samidorphan with lithium or valproate):
  - Adults—At first, 10 milligrams (mg) olanzapine and 10 mg samidorphan once a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 20 mg olanzapine and 10 mg samidorphan per day.
  - Children—Use and dose must be determined by your doctor.

Modifications

In some individuals, the body may handle Lybalvi differently. For this reason, your healthcare provider may choose to discontinue your Lybalvi or modify your dosage depending on certain factors.

Pregnancy

Newborns exposed to this medication during the third trimester of pregnancy may develop extrapyramidal (drug-induced movements) or withdrawal symptoms after birth.

Contact your healthcare provider if you're pregnant or plan to become pregnant. A pregnancy exposure registry monitors pregnancy outcomes in people exposed to atypical antipsychotics, including Lybalvi, during pregnancy. Your healthcare provider may ask you to enroll if you take Lybalvi while pregnant.

Lactation

Olanzapine, one of the ingredients in Lybalvi, crosses through breast milk, which may be toxic for the infant. There is no data on the presence of Lybalvi in human milk, the effects on the breastfed infant, or milk production. Talk to your healthcare provider about breastfeeding while taking this medication. Watch for symptoms of excess sedation, irritability, poor feeding, and tremors or abnormal muscle movements in breastfed infants.

Advanced Age

Healthcare providers may prescribe a lower dosage of Lybalvi to older people who may have decreased clearance or respond differently to the drug.

Those with dementia-related psychosis treated with Lybalvi are at an increased risk of death and, thus, should not be prescribed Lybalvi.

Liver or Kidney Impairment

No dose adjustment is necessary for people with mild or moderate liver or kidney impairment. However, this medication is not recommended for those with end-stage renal disease. Let your healthcare provider know if you have a history of liver or kidney problems.

Missed Dose

If you forget to take a dose of your medication, do not panic. You can take the missed dose on the same day unless it is too close to the time of your next dose. If it is too close to the next dose (within 12 hours), skip the missed dose. Resume the regular dosing schedule the following day.

Do not take extra to make up for the missed dose. Call your healthcare provider or pharmacist if you need help.

Overdose: What Happens If I Take Too Much Lybalvi?

Taking too much Lybalvi can lead to serious harm and may require hospital admission. If you've taken more of your medication than prescribed, immediately contact your healthcare provider or poison control for medical guidance.

Overdose symptoms related to olanzapine, a component of Lybavi, have included:

Agitation or aggressiveness
Difficulty speaking
Tachycardia (rapid heart rate)
Extrapyramidal symptoms (drug-induced movement disorders)
Sedation

What Happens If I Overdose on Lybalvi?

If you think you or someone else may have overdosed on Lybalvi, call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking Lybalvi, call 911 immediately.

911

Precautions

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

This medicine may increase your risk for opioid overdose. Do not use this medicine if you are also using opioid medicines. Wait at least 7 days after you stopped taking short-acting opioids and at least 14 days after you stopped taking long-acting opioids before you start this medicine. Do not start taking opioid medicines for at least 5 days after treatment with this medicine.

Tell your doctor if you are pregnant or planning to become pregnant. This medicine may cause unwanted effects to newborn babies if used during the later part of pregnancy.

Check with your doctor right away if you have difficulty with breathing, a fast heartbeat, a high fever, high or low blood pressure, increased sweating, loss of bladder control, seizures, severe muscle stiffness, unusually pale skin, or tiredness. These could be symptoms of a serious condition called neuroleptic malignant syndrome (NMS).

This medicine may cause a condition called drug reaction with eosinophilia and systemic symptoms (DRESS). Call your doctor right away if you have a black, tarry stools, chest pain, chills, cough, fever, painful or difficult urination, sore throat, sores, ulcers, or white spots on the lips or in the mouth, swollen glands, unusual bleeding or bruising, or unusual tiredness or weakness after using this medicine.

This medicine may increase the amount of sugar in your blood. Check with your doctor right away if you have increased thirst or increased urination. If you have diabetes, you may notice a change in the results of your urine or blood sugar tests. If you have any questions, check with your doctor.

This medicine may increase your cholesterol and fats in the blood. If this condition occurs, your doctor may give you or your child some medicines that can lower the amount of cholesterol and fats in the blood.

This medicine may increase your weight. Your doctor may need to check your or your child's weight on a regular basis while you are using this medicine.

This medicine may cause tardive dyskinesia (a movement disorder). Check with your doctor right away if you have lip smacking or puckering, puffing of the cheeks, rapid or worm-like movements of the tongue, uncontrolled chewing movements, or uncontrolled movements of the arms and legs.

Dizziness, lightheadedness, or fainting may occur, especially when you get up from a lying or sitting position. Getting up slowly may help. If this problem continues or gets worse, check with your doctor.

This medicine may add to the effects of alcohol and other central nervous system (CNS) depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicines for allergies or colds, sedatives, tranquilizers, or sleeping medicines, prescription pain medicines or narcotics, medicines for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any CNS depressants while you are taking this medicine.

Olanzapine and samidorphan may cause drowsiness, trouble with thinking, trouble with controlling body movements, or trouble with your vision, which may lead to falls, fractures or other injuries. Make sure you know how you react to this medicine before you drive, use machines, or do other jobs that require you to be alert, well-coordinated, or able to think or see well.

This medicine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, painful or difficult urination, sore throat, sores, ulcer, or white spots in the mouth, trouble breathing, unusual bleeding or bruising, or unusual tiredness or weakness.

This medicine may make it more difficult for your body to cool down. It might reduce how much you sweat. Your body could get too hot if you do not sweat enough. If your body gets too hot, you might feel dizzy, weak, tired, or confused. You might vomit or have an upset stomach. Do not get too hot while you are exercising. Avoid places that are very hot. Call your doctor if you are too hot and can not cool down.

Check with your doctor right away if you have unexpected or excess milk flow from breasts, absent, missed, or irregular menstrual periods, stopping of menstrual bleeding, swelling of the breasts or breast soreness in both females and males, loss in sexual ability, desire, drive, or performance, decreased interest in sexual intercourse, or inability to have or keep an erection. These may be symptoms of high prolactin levels in the body (eg, galactorrhea, amenorrhea, gynecomastia, and impotence).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines) and herbal or vitamin supplements.

What Are Reasons I Shouldn’t Take Lybalvi?

Do not take Lybalvi if:

You are allergic to it or any of its components
You are using opioids
You are undergoing acute opioid withdrawal

What Other Medications Interact With Lybalvi?

Lybalvi can interact with other drugs. Before starting treatment, tell your healthcare provider about all medications, including prescription and over-the-counter (OTC) drugs, vitamins, or herbal supplements you take.

Types of drugs that can interact with Lybalvi include:

Opioids: You should not take Lybalvi with opioid medications. You must not have taken short-acting or long-acting opioids for at least one week (seven days) and at least two weeks (14 days), respectively, before taking olanzapine and samidorphan. Moreover, because samidorphan is an opioid antagonist, it may make opioid treatment less effective if you take opioids shortly after stopping Lybalvi. Examples of short-acting opioids are codeine and hydrocodone. Examples of long-acting opioids are oxycodone and transdermal fentanyl.
Strong CYP3A4 inducers: CYP3A4 is a liver enzyme responsible for breaking down and clearing out certain drugs from the body. CYP3A4-inducing medications encourage CYP3A4 to break down Lybalvi quickly. This may lead to lower levels of the drug in the body, resulting in decreased effectiveness. Taking strong CYP3A4 inducers with Lybalvi is not recommended. Strong CYP3A4 inducers include rifampin.
Potent CYP1A2 inhibitors: CYP1A2 is another type of liver enzyme that metabolizes drugs. CYP1A2-inhibiting medications prevent CYPA12 from working as well. This may lead to higher levels of olanzapine and samidorphan in the body. Taking these medications together may increase the risk of Lybalvi's adverse reactions. Your healthcare provider may reduce your dosage. Strong CYP1A2 inhibitors include Luvox (fluvoxamine)

CYP1A2 inducers: Taking these medications with Lybalvi may reduce how well Lybalvi works. Your healthcare provider may increase the dosage of the olanzapine component. An example of a CYPA12 inducer is Tegretol (carbamazepine)
Valium (diazepam), alcohol, or drugs that affect the central nervous system: Taking these with Lybalvi may worsen the risk of orthostatic hypotension.
Anticholinergic drugs: Coadministration may increase the risk for severe gastrointestinal adverse reactions. Examples include antipsychotics like Clozaril (clozapine), tricyclic antidepressants, such as amitriptyline, and common OTC drugs, like Benadryl (diphenhydramine).
Antihypertensive (blood pressure-lowering) agents: Lybalvi may enhance the effects of these medications. Examples include Vasotec (enalapril) and Altace (ramipril).
Levodopa and dopamine agonists: Lybalvi may block the effects of levodopa and dopamine agonists. Examples of dopamine agonists are Mirapex (pramipexole) and Requip (ropinirole). Using these medications together is not recommended.

Talk with your pharmacist or healthcare provider for more detailed information about medication interactions with Lybalvi.

What Medications Are Similar?

Other medications used to treat both schizophrenia and bipolar disorder I include:

Olanzapine

Zyprexa (olanzapine) is an antipsychotic prescribed for schizophrenia or bipolar disorder. It is available as a tablet or an orally disintegrating tablet that easily dissolves in your saliva. It is also available as an injection under a special program for treating acute agitation associated with schizophrenia and bipolar I mania.

Treatment with olanzapine alone is associated with more weight gain than treatment with combined olanzapine and samidorphan.

Cariprazine

Vraylar is an antipsychotic used to treat schizophrenia and certain forms of bipolar disorder in adults. Vraylar may cause uncontrolled movements in your face, tongue, or other body parts, a condition known as tardive dyskinesia. Sometimes, it can start or continue to last after Vraylar has been stopped.

Aripiprazole

Aripiprazole is an orally prescribed prescription medication used to treat many psychiatric and neurological disorders, including schizophrenia, bipolar disorder, irritability associated with autism, and other conditions in people six years and older. It is also available in other formulations, like oral disintegrating tablets and as a liquid suspension, making it a suitable option for children.

This is a list of drugs also prescribed for schizophrenia and bipolar disorder I. It is NOT a list of drugs recommended to take with Lybalvi. In fact, you should not take these drugs together. Talk to your pharmacist or a healthcare provider if you have questions.

Frequently Asked Questions

Why does Lybalvi have a boxed warning?

This medication has a boxed warning, the highest safety-related warning assigned by the FDA to a drug label. The boxed warning states that Lybalvi increases the risk of death in older people with confusion and memory loss (dementia). Therefore, it is not approved for treating dementia-related psychosis.
What drugs should not be taken with Lybalvi?

You should not start Lybalvi for at least one to two weeks after stopping opioid treatment, depending on whether you were taking short- or long-acting opioids. Do not use opioids while you are on Lybalvi.
Lybalvi may also interact with the following types of medications:
·      Strong CYP3A4 inducers
·      Strong CYP1A2 inhibitors
·      CYP1A2 inducers
·      Diazepam, alcohol, or drugs that affect the central nervous system
·      Anticholinergic drugs
·      Antihypertensive agents
·      Levodopa and dopamine agonists
Talk to your healthcare provider or pharmacist for more detailed information on drug interactions.
Will I gain weight on Lybalvi?

Studies have shown that Lybalvi causes less weight gain and a smaller increase in waist circumference compared with olanzapine alone. However, weight gain is still the most common adverse event with this drug. You should monitor your weight before and during Lybalvi. Samidorphan appears to reduce olanzapine-induced weight gain.

How Can I Stay Healthy While Taking Lybalvi?

A mental health condition like schizophrenia or bipolar disorder can affect your daily functioning. While living with a mental health condition can be challenging, coping strategies, such as these, can help:

Taking prescriptions as directed by your healthcare provider
Getting enough sleep
Consuming a healthy diet
Exercising regularly
Managing your stress

Be patient. Do not stop this medication without talking to your healthcare provider. It may take a few weeks before you see your symptoms improve and stopping suddenly may have harmful effects.

If you forget to take your doses, consider using your cell phone or smart devices to set up reminders.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended to replace medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

7 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

U.S. Food and Drug Administration. Lybalvi label.
Chaudhary AMD, Khan MF, Dhillon SS, et al. A review of samidorphan: a novel opioid antagonist. Cureus. 2019;11(7):e5139. doi:10.7759/cureus.5139
Potkin SG, Kunovac J, Silverman BL, et al. Efficacy and safety of a combination of olanzapine and samidorphan in adult patients with an acute exacerbation of schizophrenia: outcomes from the randomized, phase 3 ENLIGHTEN-1 study. J Clin Psychiatry. 2020;81(2):19m12769. doi:10.4088/JCP.19m12769
Correll CU, Newcomer JW, Silverman B, et al. Effects of olanzapine combined with samidorphan on weight gain in schizophrenia: a 24-week phase 3 study. Am J Psychiatry. 2020;177(12):1168-1178. doi:10.1176/appi.ajp.2020.19121279
U.S. Food and Drug Administration. Zyprexa label.
U.S. Food and Drug Administration. Vraylar label.
U.S. Food and Drug Administration. Abilify label.

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Lybalvi (Olanzapine and Samidorphan) - Oral