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Lybalvi

Lybalvi (Olanzapine and Samidorphan Tablets) side effects drug center

 

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SIDE EFFECTS

Lybalvi Side Effects Center

What Is Lybalvi?

Lybalvi (olanzapine and samidorphan) is a combination of an atypical antipsychotic and an opioid antagonist used to treat schizophrenia in adults and bipolar I disorder in adults, for acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate and for maintenance monotherapy treatment.

What Are Side Effects of Lybalvi?

Side effects of Lybalvi include:

Dosage for Lybalvi

The recommended starting dose of Lybalvi to treat schizophrenia is 5mg/10mg or 10 mg/10 mg. The recommended starting dose of Lybalvi to treat bipolar I disorder (manic or mixed episodes) is 10mg/10mg or 15 mg/10 mg. The recommended starting dose of Lybalvi to treat bipolar I disorder as an adjunct to lithium or valproate is 10mg/10mg.


Lybalvi In Children

The safety and effectiveness of Lybalvi have not been established in pediatric patients.

What Drugs, Substances, or Supplements Interact with Lybalvi?
 

Lybalvi may interact with other medicines such as:

  • strong CYP3A4 inducers,
  • strong CYP1A2 inhibitors,
  • CYP1A2 inducers,
  • diazepam, alcohol, and other central nervous system (CNS) acting drugs,
  • anticholinergic drugs,
  • antihypertensive drugs,
  • levodopa and dopamine agonists, and
  • opioids.

Tell your doctor all medications and supplements you use.


Lybalvi During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Lybalvi; neonates exposed to antipsychotic drugs, including the olanzapine component of Lybalvi, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including Lybalvi, during pregnancy. Olanzapine passes into breast milk and there are reports of excess sedation, irritability, poor feeding and extrapyramidal symptoms (tremors and abnormal muscle movements) in infants exposed to olanzapine through breast milk. Infants exposed to Lybalvi should be monitored for excess sedation, irritability, poor feeding and extrapyramidal symptoms (tremors and abnormal muscle movements). Consult your doctor before breastfeeding.

Additional Information

Our Lybalvi (olanzapine and samidorphan) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is LYBALVI and how is it used?

LYBALVI is a prescription medicine which contains 2 medicines (olanzapine and samidorphan) used in adults:

It is not known if LYBALVI is safe or effective in children.

What are the possible side effects of LYBALVI?

LYBALVI may cause serious side effects, including:

You can accidentally overdose in 2 ways:

It is important that you 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:

Tell your healthcare provider if you are taking LYBALVI before a medical procedure or surgery.

  • See "What is the most important information I should know about LYBALVI?"
  • Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death.
  • Opioid withdrawal. Do not take LYBALVI for at least 7 days after you stopped taking short-acting opioids and for at least 14 days after you stopped taking long-acting opioids. One of the medicines in LYBALVI (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 LYBALVI. One of the medicines in LYBALVI (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 LYBALVI.
    • LYBALVI blocks the effects of opioids, such as heroin, methadone, or opioid pain medicines. Do not take large amounts of opioids to try to overcome the opioid-blocking effects of LYBALVI. This can lead to serious injury, coma, or death.
    • After you take LYBALVI, its blocking effect slowly decreases and completely goes away over time. You may be more sensitive to the effects of opioids. If you have used opioid street drugs or opioid-containing medicines in the past, using opioids in amounts that you used before treatment with LYBALVI can lead to overdose or death.
    • have trouble breathing
    • become very drowsy with slowed breathing
    • have slow, shallow breathing (little chest movement with breathing)
    • feel faint, very dizzy, confused, or have unusual symptoms
  • Neuroleptic malignant syndrome (NMS), 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 LYBALVI (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 o kidney problems
    • liver problems o lung problems
    • heart problems
  • Problems with your metabolism such as:

    Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with LYBALVI:

    • high blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take LYBALVI. 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 LYBALVI.
      • 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 LYBALVI.
    • weight gain. You and your healthcare provider should check your weight before you start and often during treatment with LYBALVI.
  • Uncontrolled body movements (tardive dyskinesia). LYBALVI may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking LYBALVI. Tardive dyskinesia may also start after you stop taking LYBALVI.
  • 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. LYBALVI 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 count. Your healthcare provider may do blood tests during the first few months of treatment with LYBALVI.
  • 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. See “What should I avoid while taking LYBALVI?”
  • Increased prolactin levels in your blood. Your healthcare provider may do blood tests to check your prolactin levels during treatment with LYBALVI.

The most common side effects of LYBALVI when used to treat people with schizophrenia include:

  • weight gain
  • sleepiness
  • dry mouth
  • headache

The most common side effects of LYBALVI when used alone to treat people with mixed or manic episodes that happen with bipolar I disorder include:

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

The most common side effects of LYBALVI when used in combination with lithium or valproate to treat people with mixed or manic episodes that happen with bipolar I disorder include:

  • dry mouth
  • weight gain
  • increased appetite
  • dizziness
  • back pain
  • constipation
  • problems speaking
  • mouth watering
  • memory problems
  • numbness and tingling in your arm and legs

These are not all the possible side effects of LYBALVI.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA1088.

 

Lybalvi Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in detail in other sections of the labeling:

  • Increased Mortality in Elderly Patients with Dementia-related Psychosis [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
  • Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis [see WARNINGS AND PRECAUTIONS]
  • Precipitation of Opioid Withdrawal in Patients Who Are Dependent on Opioids [see WARNINGS AND PRECAUTIONS]
  • Vulnerability to Life-Threatening Opioid Overdose [see WARNINGS AND PRECAUTIONS]
  • Neuroleptic Malignant Syndrome [see WARNINGS AND PRECAUTIONS]
  • Drug Reaction with Eosinophilia and Systemic Symptoms [see WARNINGS AND PRECAUTIONS]
  • Metabolic Changes [see WARNINGS AND PRECAUTIONS]
  • Tardive Dyskinesia [see WARNINGS AND PRECAUTIONS]
  • Orthostatic Hypotension and Syncope [see WARNINGS AND PRECAUTIONS]
  • Falls [see WARNINGS AND PRECAUTIONS]
  • Leukopenia, Neutropenia, and Agranulocytosis [see WARNINGS AND PRECAUTIONS]
  • Dysphagia [see WARNINGS AND PRECAUTIONS]
  • Seizures [see WARNINGS AND PRECAUTIONS]
  • Potential for Cognitive and Motor Impairment [see WARNINGS AND PRECAUTIONS]
  • Body Temperature Regulation [see WARNINGS AND PRECAUTIONS]
  • Anticholinergic (Antimuscarinic) Effects [see WARNINGS AND PRECAUTIONS]
  • Hyperprolactinemia [see WARNINGS AND PRECAUTIONS]
  • Risks Associated with Combination Treatment with Lithium or Valproate [see WARNINGS AND PRECAUTIONS]

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse Reactions In Patients With Schizophrenia

Patient Exposure

The safety of LYBALVI was evaluated in 1262 patients (18 to 67 years of age) diagnosed with schizophrenia in four double-blind, controlled studies and three long-term safety extension studies of up to 3 years of duration. This experience corresponds to approximately 910 person-years. In these studies, there were a total of 663 patients exposed to LYBALVI for at least 6 months, and 386 patients for at least one year.

Adverse Reactions In The Short-Term (4 week) Placebo-Controlled Trial In Adults With Schizophrenia

The most common adverse reactions (incidence of at least 5% of patients exposed to LYBALVI and greater than twice the rate of placebo) are weight increased, somnolence, dry mouth, and headache.

Adverse reactions associated with the use of LYBALVI (incidence of 2% or greater and greater than in placebo-treated patients) are shown in Table 2.

Table 2: Adverse Reactions Reported in ≥2% of LYBALVI-Treated Patients and Greater than Placebo in a 4-Week Schizophrenia Trial

Adverse Reaction Placebo
(N=134) %		 LYBALVI (10 mg/10 mg, 20 mg/10 mg)
(N=134) %
Weight increased 3 19
Somnolence 2 9
Dry mouth 1 7
Headache 3 6
Blood insulin increased 1 3
Sedation 0 2
Dizziness 1 2
Neutrophil count decreased 0 2

Adverse reactions that led to discontinuation in LYBALVI-treated patients in the short-term placebo-controlled trial in adults with schizophrenia include schizophrenia (1%) and abnormal liver function tests (1%).

Adverse Reactions In The Long-Term (24-week), Active-Controlled Trial In Adults With Schizophrenia

In the 24-week, olanzapine-controlled trial in patients with stable schizophrenia, adverse reactions associated with the use of LYBALVI (incidence of 2% or greater) include: weight increased (25%), somnolence (21%), dry mouth (13%), increased appetite (11%), waist circumference increased (6%), blood creatine phosphokinase increased (5%), headache (4%), lethargy (4%), sedation (4%), akathisia (3%), alanine aminotransferase increased (3%), aspartate aminotransferase increased (3%), constipation (3%), dizziness (3%), fatigue (3%), nausea (3%), blood pressure increased (3%), neutrophil count decreased (3%), blood insulin increased (2%), weight decreased (2%), and dyslipidemia (2%).

Adverse reactions that led to LYBALVI treatment discontinuation in more than one patient include somnolence (2%), weight increased (2%), neutropenia (2%), glycosylated hemoglobin increased (1%), schizophrenia (1%), and liver function test abnormal (1%).

Hyperglycemia

Mean increases in blood glucose have been observed in patients treated (median exposure of 9.2 months) with olanzapine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). The mean increase of serum glucose (fasting and nonfasting samples) from baseline to the average of the 2 highest serum concentrations was 15.0mg/dL. Hyperglycemia, as defined by fasting glucose ≥126 mg/dL, has been observed in patients treated with LYBALVI.

In the 4-week placebo-controlled trial in adult patients with schizophrenia, shifts in fasting glucose from normal to high occurred in 4% of patients treated with LYBALVI, 1% of patients treated with olanzapine, and no patients treated with placebo.

In the 24-week olanzapine-controlled trial, patients treated with LYBALVI were more likely to experience abnormal shifts in glycemic parameters than patients treated with olanzapine (Table 3).

Table 3: Changes in Glycemic Parameters in a 24-Week Trial of Patients with Schizophrenia

LYBALVI Olanzapine
Proportion of Patients with Shifts, % (n/N)*
Glucose Normal to High (<100 mg/dL to ≥126 mg/dL) 12 (26/223) 8(18/219)
Impaired (≥100 mg/dL and <126 mg/dL) to High (≥126 mg/dL) 24 (9/38) 11(5/47)
Increase ≥10 mg/dL 66 (174/265) 57 (154/270)
Hemoglobin A1c Normal (<5.7%) to Impaired (≥5.7% and <6.5%) 42 (86/204) 35 (68/197)
Normal to High (<5.7% to ≥6.5%) 0.5 (1/204) 1.5 (3/197)
Impaired (≥5.7% and <6.5%) to High (≥6.5%) 9.5 (6/63) 9.2 (7/76)
* n: number of patients with reported abnormal shifts; N: number of patients who had assessments at both baseline and endpoint for mean change, or normal at baseline and at least 1 post-baseline assessment for shift.

Dyslipidemia

In the 4-week, placebo-controlled trial in adult patients with schizophrenia, shifts in fasting triglycerides from normal to high occurred in 14% of patients treated with LYBALVI and 4% of patients treated with placebo.

In the 24-week olanzapine-controlled study, mean changes in fasting total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were similar in patients treated with LYBALVI and in patients treated with olanzapine.

Weight Gain

In the 4-week placebo-controlled study in adult patients with schizophrenia, mean changes in weight, and proportion of patients with ≥7% weight increase, were greater in patients treated with LYBALVI and olanzapine than in patients on placebo. In that study, mean weight gain was 3.0 kg in patients treated with LYBALVI, 2.4 kg in patients treated with olanzapine, and 0.2 kg in patients treated with placebo. The proportion of patients with ≥7% weight increase was 26% in patients treated with LYBALVI, 20% in patients treated with olanzapine, and 5% in patients treated with placebo.

In the 24-week trial, LYBALVI-treated patients gained on average 4.2% of baseline body weight. The proportion of patients treated with LYBALVI with ≥10% body weight gain was 17.8% [see Clinical Studies].

Extrapyramidal Symptoms

In the 4-week placebo-controlled trial in adult patients with schizophrenia, patients were assessed using the Simpson-Angus Rating Scale (SAS) for extrapyramidal symptoms (EPS)  (total score ranges from 1 to 14), the Barnes Akathisia Rating Scale (BARS) for akathisia (total score ranges from 0 to 14), and the Abnormal Involuntary Movement Scale (AIMS) for dyskinesias (total score ranges from 0 to 28). The mean changes from baseline to last study visit for the SAS, BARS, and AIMS was similar in LYBALVI-treated patients and in placebo-treated patients. The mean changes for LYBALVI- vs placebo-treated patients were 0.00 vs -0.2 for AIMS, 0.0 vs -0.1 for BARS, and 0.0 vs -0.3 for SAS, respectively. The rate of parkinsonism (SAS total score >3) was lower in patients treated with LYBALVI (4%) compared to those on placebo (10%). The rates of akathisia (BARS global clinical assessment score ≥2) and dyskinesia (AIMS score ≥3 on any of the first 7 items, or a score ≥2 on two or more of any of the first 7 items) were similar in patients treated with LYBALVI and in those on placebo. Rates of akathisia were 6.0% and 8.2% in patients treated with LYBALVI and placebo, respectively, and the rate of dyskinesia was 1.5% both in LYBALVI-treated and in placebo-treated patients.

The frequency of reported adverse reactions related to extrapyramidal symptoms, including akathisia, restlessness, muscle spasms, bradykinesia, tremor, extrapyramidal disorder, and parkinsonism was 2% both in LYBALVI-treated and in placebo-treated patients.

In the 24-week active-controlled trial, the mean change from baseline to the last visit for the SAS, BARS, and AIMS was similar in LYBALVI-treated patients and in those treated with the active control. Extrapyramidal adverse reactions, including parkinsonism, akathisia, and dyskinesia, had a similar incidence in LYBALVI-treated patients and in those treated with the active control: any extrapyramidal symptom was 8%, akathisia was 3%.

Dystonia

Symptoms of dystonia, (prolonged abnormal contractions of muscle groups) may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. Although these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first-generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Adverse Reactions In Patients With Bipolar Disorder

The safety of LYBALVI for the treatment of bipolar I disorder (mixed or manic) monotherapy and adjunct to lithium or valproate relies on information fromadequate and well-controlled studies of olanzapine tablets in bipolar I disorder.

The most common adverse reactions (incidence of at least 5% of patients exposed to olanzapine and greater than or equal to twice the rate of placebo) from short-term trials of olanzapine (manic or mixed episodes) are somnolence, dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite, and tremor.

The most common adverse reactions (incidence of at least 5% of patients exposed to olanzapine and greater than or equal to twice the rate of placebo) from short-term trials of olanzapine as adjunct to lithium or valproate (manic or mixed episodes) are dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of olanzapine. Because these reactions are reported voluntarily from a population of uncertain size, it is difficult to reliably estimate their frequency or evaluate a causal relationship to drug exposure.

  • allergic reactions (e.g., anaphylactoid reaction, angioedema, pruritus or urticaria)
  • cholestatic or mixed liver injury, hepatitis, jaundice
  • diabetic coma, diabetic ketoacidosis
  • discontinuation reaction (diaphoresis, nausea or vomiting)
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
  • hyperlipidemia (random cholesterol levels of ≥240mg/dL and random triglyceride levels of ≥1000 mg/dL have been reported)
  • neutropenia
  • pancreatitis
  • priapism
  • rash
  • restless legs syndrome
  • rhabdomyolysis
  • salivary hypersecretion
  • stuttering1
  • venous thromboembolic events (including pulmonary embolism and deep venous thrombosis)

DRUG INTERACTIONS

Effects Of Other Drugs On LYBALVI

Table 4 describes clinically significant drug interactions where the concomitant use of other drugs affects LYBALVI.

Table 4: Effects of Other Drugs on LYBALVI

Strong CYP3A4 Inducer
Clinical Implication: Coadministration of LYBALVI with a strong CYP3A4 inducer decreases AUCinf of olanzapine and samidorphan [see CLINICAL PHARMACOLOGY], which may reduce LYBALVI efficacy.
Prevention or Management: Concomitant use of LYBALVI with strong CYP3A4 inducers is not recommended.
Strong CYP1A2 Inhibitor
Clinical Implication: Concomitant use of LYBALVI with a strong CYP1A2 inhibitor increases olanzapine AUC and Cmax [see CLINICAL PHARMACOLOGY], which may increase the risk of LYBALVI adverse reactions.
Prevention or Management: Consider reducing the dosage of the olanzapine component in LYBALVI when used concomitantly with strong CYP1A2 inhibitors.
CYP1A2 Inducer
Clinical Implication: Concomitant use of LYBALVI with CYP1A2 inducers decreases olanzapine exposure [see CLINICAL PHARMACOLOGY], which may reduce LYBALVI efficacy.
Prevention or Management: Consider increasing the dosage of the olanzapine component in LYBALVI when used concomitantly with CYP1A2 inducers.
Diazepam, Alcohol, and Other CNS Acting Drugs
Clinical Implication: Concomitant use of diazepam, alcohol, or other CNS acting drugs with LYBALVI may potentiate the orthostatic hypotension observed with olanzapine [see WARNINGS AND PRECAUTIONS].
Prevention or Management: LYBALVI should be used with caution in patients receiving concomitantly diazepam or other CNS acting drugs, or using alcohol.
Anticholinergic Drugs
Clinical Implication: Concomitant treatment with olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility.
Prevention or Management: LYBALVI should be used with caution in patients receiving medications having anticholinergic (antimuscarinic) effects [see WARNINGS AND PRECAUTIONS].

Effects Of LYBALVI On Other Drugs

Table 5 describes clinically significant drug interactions where concomitant use of LYBALVI affects other drugs.

Table 5: Effects of LYBALVI on Other Drugs

Antihypertensive Agents
Clinical Implication: LYBALVI may enhance the effects of certain antihypertensive agents.
Prevention or Management: Monitor blood pressure and reduce dosage of antihypertensive drug in accordance with its approved product labeling.
Levodopa and Dopamine Agonists
Clinical Implication: LYBALVI may antagonize the effects of levodopa and dopamine agonists.
Prevention or Management: Concomitant use of LYBALVI is not recommended with levodopa and dopamine agonists.

Opioids

LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal [see CONTRAINDICATIONS].

LYBALVI increases the risk of precipitating acute opioid withdrawal in patients who are dependent on opioids. Prior to initiating LYBALVI, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].

In emergency situations, if a LYBALVI-treated patient requires opioid treatment for anesthesia or analgesia, discontinue LYBALVI. The opioid should be administered by properly trained individual(s), and the patient should be properly monitored in a setting equipped and staffed for cardiopulmonary resuscitation [see WARNINGS AND PRECAUTIONS].

In non-emergency situations, if a LYBALVI-treated patient is expected to require opioid treatment (e.g., for analgesia during or after an elective surgical procedure) discontinue LYBALVI at least 5 days before opioid treatment and start olanzapine or another antipsychotic, if needed.

Given that LYBALVI contains samidorphan, an opioid antagonist, opioid treatment may be less effective or ineffective shortly after LYBALVI discontinuation because of the presence of samidorphan.

REFERENCES

1 Stuttering was only studied in oral and long acting injection (LAI) formulations.

Read the entire FDA prescribing information for Lybalvi (Olanzapine and Samidorphan Tablets)

&Copy; Lybalvi Patient Information is supplied by Cerner Multum, Inc. and Lybalvi Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.