Indications: LYBALVI® is indicated for the treatment of adults with bipolar I disorder for acute treatment of manic or mixed episodes as monotherapy and as an adjunct to lithium or valproate, or as a maintenance monotherapy treatment, or for the treatment of adults with schizophrenia.

Actor portrayal of a patient with a bird in flight
Actor portrayal of a patient with a bird in flight

POWER TO TREAT SCHIZOPHRENIA1

Actor portrayal.

Study Design

ENLIGHTEN-1 and ENLIGHTEN-1 safety extension

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  • The ENLIGHTEN-1 pivotal study was a 4-week, randomized, double-blind, placebo-controlled Phase 3 study evaluating adults with schizophrenia experiencing an acute exacerbation. Patients were randomized 1:1:1 to LYBALVI, olanzapine, or placebo. The primary endpoint was change from baseline in the PANSS total score, and the secondary endpoint was change from baseline in the CGI-S score2
  • The ENLIGHTEN-1 safety extension study contained patients who completed the 4-week trial. The study assessed the safety and tolerability of LYBALVI, as well as durability of treatment effect, as measured by PANSS and CGI-S scores over 52 weeks in an open-label Phase 3 extension study3
ENLIGHTEN-1 safety extension study limitations
    • Open-label study design with loss of randomization, potential differential dropout of patients, and no comparator arm limits interpretation of efficacy and safety3
    • Missing data may have impacted the findings as approximately one-third of patients discontinued before 52 weeks3
    • In this study, patients’ baseline characteristics were affected by prior treatment with LYBALVI, olanzapine, or placebo in the antecedent study3

Diagram illustrating the clinical study design, phases, and treatment arms.

Swipe chart to see more

aDosing was flexible for the first 2 weeks and fixed thereafter. Patients were instructed to take 1 tablet by mouth each day, preferably at bedtime.2,4

bAll patients started the safety extension study on a 10 mg/10 mg dose of LYBALVI. The LYBALVI dose could be increased to 15 mg/10 mg or 20 mg/10 mg.3

cThe safety population consisted of patients who received ≥1 dose of study drug. The efficacy population consisted of patients who received ≥1 dose of study drug and had ≥1 postbaseline PANSS assessment.3

ENLIGHTEN-1 Pivotal Study

  • ENLIGHTEN-1 was a 4-week, randomized, double-blind, placebo-controlled Phase 3 study (N=403) evaluating adults with schizophrenia experiencing an acute exacerbation2
  • The primary endpoint was change from baseline in the PANSS total score, and the secondary endpoint was change from baseline in the CGI-S score2
Select inclusion criteria2
  • Met DSM-V schizophrenia criteria
  • 18-70 years of age
  • BMI 18-40 kg/m2
  • PANSS total score ≥80 with a score ≥4 on at least 3 of the selected positive scale items
  • CGI-S score ≥4
Select exclusion criteria2
  • History of diabetes
  • Olanzapine use 6 months prior to study
Prior antipsychotic medications2

Prior to study entry, 89% of participants had taken at least one antipsychotic, including risperidone, haloperidol, quetiapine, and aripiprazole.

ENLIGHTEN-1 Safety Extension Study3

  • This 52-week, multicenter, open-label Phase 3 extension study (N=281) evaluated the long-term safety and durability of effect of LYBALVI in adults with schizophrenia who completed the 4-week trial
  • Patients initiated treatment with LYBALVI 10 mg/10 mg. The dose could be increased to 15 mg/10 mg or 20 mg/10 mg based on tolerability and clinical need
  • The study assessed long-term safety and tolerability, as well as durability of treatment effect as measured by PANSS and CGI-S scores over 52 weeks
PANSS Score

Reduction in PANSS total score over time

LYBALVI (olanzapine and samidorphan) provided powerful efficacy with significantly reduced PANSS total scores at 4 weeks2

Continued durability of treatment effect was observed through 52 weeks3

Mean PANSS total score over time1,3-5

The PANSS total score ranges from 30 to 210

Line graph showing PANSS total scores decreasing over time across treatment groups, with continued improvement during a 52-week LYBALVI extension phase.

Swipe chart to see more

In the ENLIGHTEN-1 pivotal study, separation of PANSS total score between LYBALVI and placebo was observed starting at Week 22
Pivotal study2

ENLIGHTEN-1 was not designed to compare the efficacy of LYBALVI to the efficacy of olanzapine. Comparative conclusions of efficacy between LYBALVI and olanzapine cannot be drawn.

  • ENLIGHTEN-1 pivotal study primary endpoint: Significant improvement in change from baseline PANSS total score with LYBALVI vs placebo at Week 4 (23.9-point reduction vs 17.5, respectively; P<0.001)
  • Secondary endpoint: LS mean difference in CGI-S change from baseline vs placebo at Week 4 was -0.38±0.12 (P=0.002) for patients taking LYBALVI
  • Early discontinuation rates: 9% (n=12) in the LYBALVI group, and 17% (n=23) in the placebo group
  • The inclusion of samidorphan in LYBALVI did not appear to negatively impact the antipsychotic efficacy of olanzapine
Safety extension: Durability assessment3

The ENLIGHTEN-1 safety extension study was an open-label safety study in which all participants received LYBALVI. This study was not designed to compare efficacy based on prior treatment group from ENLIGHTEN-1, nor was it designed to prospectively assess or evaluate the effect of LYBALVI on PANSS total score. No conclusions of efficacy can be drawn from these data.

  • PANSS and CGI-S were exploratory endpoints in this study; no conclusions of efficacy can be drawn from these data
  • Mean change from baseline for PANSS total score (95% CI) was -16.2 (-18.5 to -14.0) at 52 weeks
  • Change from baseline in PANSS total score was summarized using last observation carried forward for missing data and was based on observed data
  • Mean change in CGI-S score (95% CI) was -0.9 (-1.0 to -0.8) at 52 weeks
PANSS Subscale Scores

Exploratory outcomes4

  • The ENLIGHTEN-1 pivotal study and ENLIGHTEN-1 safety extension study were not powered to draw conclusions of efficacy from the individual PANSS subscales
  • The outcomes were exploratory and should be interpreted with caution
Limitations

Individual subscale scores are not validated for use in isolation to assess disease severity.5

Observed mean change from baseline in PANSS positive subscale score4

The positive subscale score ranges from 7 to 495

Data chart showing the mean change from baseline in PANSS Positive Symptom Score over time.

Swipe chart to see more

Observed mean change from baseline in PANSS negative subscale score3

The negative subscale score ranges from 7 to 495

Data chart showing the mean change from baseline in PANSS Negative Symptom Score over time.

Swipe chart to see more

Observed mean change from baseline in PANSS general psychopathology subscale score4

The general psychopathology subscale score ranges from 16 to 1125

Chart showing PANSS general psychopathology scores using lybalvi.

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Safety Profile

ENLIGHTEN-1 pivotal study

Most common adverse reactions observed with the use of LYBALVI
(incidence of ≥5% and ≥2x placebo)1
Adverse reactionLYBALVI
(10 mg/10 mg, 20 mg/10 mg)
(n=134)		Placebo (n=134)
Weight increased19%3%
Somnolence9%2%
Dry mouth7%1%
Headache6%3%

Swipe table to see more

  • No patient treated with LYBALVI discontinued the study due to these common adverse reactions2
  • The reasons for discontinuation for patients taking LYBALVI vs placebo, respectively: patient withdrawal (6% vs 6%), adverse reaction (1.5% vs 5.2%), lack of efficacy (0.7% vs 6%), and loss to follow-up (0.7% vs 0%)2
  • Adverse reactions that led to discontinuation in patients treated with LYBALVI included schizophrenia (1%) and abnormal liver function tests (1%)1
  • 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 patients treated with LYBALVI and patients treated with placebo1

For a complete list of adverse reactions, please refer to the full Prescribing Information for LYBALVI.

ENLIGHTEN-1 safety extension study

Adverse events observed with the use of LYBALVI (incidence of ≥2%)3
Adverse eventPatients (N=277)
Increased weight13%
Somnolence8%
Headache4%
Nasopharyngitis4%
Extra dose administered3%
Schizophrenia3%
Anxiety3%
Dry mouth3%
Social stay hospitalization3%
Decreased weight2%
Increased blood prolactin2%
Increased blood insulin2%
Insomnia2%

Swipe table to see more

Based on observed data without imputation.

Numbers rounded to the nearest percentage.

  • Adverse events were reported by 49% of patients3
  • 3% of patients reported serious adverse events3
  • 33.9% of patients discontinued before completing the safety extension study3
  • Reasons for discontinuation included patient withdrawal (15.5%), patient lost to follow-up (6.9%), adverse events (5.4%), and lack of efficacy (1.8%)3
    • The only adverse event leading to discontinuation that occurred in >1 patient was worsening/exacerbation of schizophrenia (2.2%)
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Weight gain data

The impact of LYBALVI on weight gain and related exploratory outcomes was evaluated in the ENLIGHTEN-2 and ENLIGHTEN-2 safety extension studies.

Explore weight profile

BMI=body mass index; CGI-S=Clinical Global Impressions Scale; CI=confidence interval; DSM=Diagnostic and Statistical Manual of Mental Disorders; LS=least squares; PANSS=Positive and Negative Syndrome Scale; SD=standard deviation.

References: 1. LYBALVI. Prescribing Information. Alkermes, Inc. 2. 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. 3. Yagoda S, Graham C, Simmons A, Arevalo C, Jiang Y, McDonnell D. Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study. CNS Spectr. 2021;26(4):383-392. 4. Data on file. Alkermes, Inc. 5. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261-276.

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Important Safety Information

Important Safety Information

Lybalvi HCP ISI

Boxed Warning

Boxed Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LYBALVI (olanzapine and samidorphan) is not approved for the treatment of patients with dementia-related psychosis.

ISI Copy

Contraindications:

LYBALVI is contraindicated in patients who are using opioids or are undergoing acute opioid withdrawal. If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for these products.

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis,

including stroke, transient ischemia attack, and fatalities. See Boxed Warning.

Precipitation of Severe Opioid Withdrawal in Patients who are Physiologically Dependent on Opioids:

LYBALVI can precipitate opioid withdrawal in patients who are dependent on opioids, which can lead to an opioid withdrawal syndrome, sometimes requiring hospitalization. LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. Prior to initiating LYBALVI, there should be at least a 7-day opioid-free interval from last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. Explain the risks associated with precipitated withdrawal and the importance of giving an accurate account of last opioid use to patients and caregivers.

Vulnerability to Life-Threatening Opioid Overdose:

Attempting to overcome opioid blockade with high or repeated doses of exogenous opioids could lead to life-threatening or fatal opioid intoxication, particularly if LYBALVI therapy is interrupted or discontinued, subjecting the patient to high levels of unopposed opioid agonist as the samidorphan blockade wanes. Inform patients of the potential consequences of trying to overcome the opioid blockade and the serious risks of taking opioids concurrently with LYBALVI or while transitioning off LYBALVI. In emergency situations, if a LYBALVI-treated patient requires opioid treatment as part of anesthesia or analgesia, discontinue LYBALVI. Opioids should be administered by properly trained individual(s) and patient should be continuously monitored in a setting equipped and staffed for cardiopulmonary resuscitation. Patients with a history of chronic opioid use prior to treatment with LYBALVI may have decreased opioid tolerance if LYBALVI therapy is interrupted or discontinued. Advise patients that this decreased tolerance may increase the risk of opioid overdose if opioids are resumed at the previously tolerated dosage.

Neuroleptic Malignant Syndrome,

a potentially fatal reaction. Signs and symptoms include hyperpyrexia, muscle rigidity, delirium, autonomic instability, elevated creatine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and close monitoring.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS),

a potentially fatal condition reported with exposure to olanzapine, a component of LYBALVI. Symptoms include a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. Discontinue if DRESS is suspected.

Metabolic Changes,

including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Any patient treated with LYBALVI should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required anti-diabetic treatment despite discontinuation of the suspect drug. Measure weight and assess fasting glucose and lipids when initiating LYBALVI and monitor periodically.

Tardive Dyskinesia (TD):

Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible increases with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after discontinuation. Given these considerations, LYBALVI should be prescribed in a manner that is most likely to reduce the risk of tardive dyskinesia. If signs and symptoms of TD appear, drug discontinuation should be considered.

Orthostatic Hypotension and Syncope:

Monitor orthostatic vital signs in patients who are vulnerable to hypotension, patients with known cardiovascular disease, and patients with cerebrovascular disease.

Falls:

LYBALVI may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls, and consequently, fractures or other injuries. Assess patients for risk when using LYBALVI.

Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases):

Perform complete blood counts in patients with a history of a clinically significant low white blood cell (WBC) count or history of leukopenia or neutropenia. Discontinue LYBALVI if clinically significant decline in WBC occurs in the absence of other causative factors.

Dysphagia:

Use LYBALVI with caution in patients at risk for aspiration.

Seizures:

Use LYBALVI with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment:

Because LYBALVI may cause somnolence, and may impair judgment, thinking, or motor skills, caution patients about operating hazardous machinery, including motor vehicles, until they are certain that LYBALVI does not affect them adversely.

Body Temperature Dysregulation:

Use LYBALVI with caution in patients who may experience conditions that increase core body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Anticholinergic (Antimuscarinic) Effects:

Olanzapine, a component of LYBALVI, was associated with constipation, dry mouth, and tachycardia. Use LYBALVI with caution with other anticholinergic medications and in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus or related conditions. In postmarketing experience, the risk for severe adverse reactions (including fatalities) was increased with concomitant use of anticholinergic medications.

Hyperprolactinemia:

LYBALVI elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.

Risks Associated with Combination Treatment with Lithium or Valproate:

If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for a description of the risks for these products.

Interference with Laboratory Tests for Opioid Detection:

LYBALVI may cause false positive results with urinary immunoassay methods for detecting opioids. Use an alternative analytical technique (e.g., chromatographic methods) to confirm positive opioid urine drug screen results.

Most Common Adverse Reactions observed in clinical trials were:

  • Schizophrenia (LYBALVI): weight increased, somnolence, dry mouth, and headache
  • Bipolar I Disorder, Manic or Mixed Episodes (olanzapine): somnolence, dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite, and tremor
  • Bipolar I Disorder, Manic or Mixed Episodes, adjunct to lithium or valproate (olanzapine): dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia

Concomitant Medication:

LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. Concomitant use of LYBALVI is not recommended with strong CYP3A4 inducers, levodopa and dopamine agonists. Reduce dosage of LYBALVI when using with strong CYP1A2 inhibitors. Increase dosage of LYBALVI with CYP1A2 inducers. Use caution with diazepam, alcohol, other CNS acting drugs, or in patients receiving anticholinergic (antimuscarinic) medications. Monitor blood pressure and reduce dosage of antihypertensive drug in accordance with its approved product labeling.

Pregnancy:

May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with LYBALVI. Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LYBALVI during pregnancy.

Renal Impairment:

LYBALVI is not recommended for patients with end-stage renal disease (eGFR of <15 mL/minute/1.73 m2).

To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at 1-888-235-8008 or FDA at 1-800-FDA-1088 or https://www.fda.gov/medwatch.

Indications

LYBALVI is indicated for the treatment of:

  • Bipolar I disorder in adults
    • Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate
    • Maintenance monotherapy treatment
  • Schizophrenia in adults

Please see full Prescribing Information, including Boxed Warning, for LYBALVI.

Lybalvi HCP ISI

Boxed Warning

Boxed Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LYBALVI (olanzapine and samidorphan) is not approved for the treatment of patients with dementia-related psychosis.

ISI Copy

Contraindications:

LYBALVI is contraindicated in patients who are using opioids or are undergoing acute opioid withdrawal. If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for these products.

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis,

including stroke, transient ischemia attack, and fatalities. See Boxed Warning.

Precipitation of Severe Opioid Withdrawal in Patients who are Physiologically Dependent on Opioids:

LYBALVI can precipitate opioid withdrawal in patients who are dependent on opioids, which can lead to an opioid withdrawal syndrome, sometimes requiring hospitalization. LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. Prior to initiating LYBALVI, there should be at least a 7-day opioid-free interval from last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. Explain the risks associated with precipitated withdrawal and the importance of giving an accurate account of last opioid use to patients and caregivers.

Vulnerability to Life-Threatening Opioid Overdose:

Attempting to overcome opioid blockade with high or repeated doses of exogenous opioids could lead to life-threatening or fatal opioid intoxication, particularly if LYBALVI therapy is interrupted or discontinued, subjecting the patient to high levels of unopposed opioid agonist as the samidorphan blockade wanes. Inform patients of the potential consequences of trying to overcome the opioid blockade and the serious risks of taking opioids concurrently with LYBALVI or while transitioning off LYBALVI. In emergency situations, if a LYBALVI-treated patient requires opioid treatment as part of anesthesia or analgesia, discontinue LYBALVI. Opioids should be administered by properly trained individual(s) and patient should be continuously monitored in a setting equipped and staffed for cardiopulmonary resuscitation. Patients with a history of chronic opioid use prior to treatment with LYBALVI may have decreased opioid tolerance if LYBALVI therapy is interrupted or discontinued. Advise patients that this decreased tolerance may increase the risk of opioid overdose if opioids are resumed at the previously tolerated dosage.

Neuroleptic Malignant Syndrome,

a potentially fatal reaction. Signs and symptoms include hyperpyrexia, muscle rigidity, delirium, autonomic instability, elevated creatine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and close monitoring.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS),

a potentially fatal condition reported with exposure to olanzapine, a component of LYBALVI. Symptoms include a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. Discontinue if DRESS is suspected.

Metabolic Changes,

including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Any patient treated with LYBALVI should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required anti-diabetic treatment despite discontinuation of the suspect drug. Measure weight and assess fasting glucose and lipids when initiating LYBALVI and monitor periodically.

Tardive Dyskinesia (TD):

Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible increases with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after discontinuation. Given these considerations, LYBALVI should be prescribed in a manner that is most likely to reduce the risk of tardive dyskinesia. If signs and symptoms of TD appear, drug discontinuation should be considered.

Orthostatic Hypotension and Syncope:

Monitor orthostatic vital signs in patients who are vulnerable to hypotension, patients with known cardiovascular disease, and patients with cerebrovascular disease.

Falls:

LYBALVI may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls, and consequently, fractures or other injuries. Assess patients for risk when using LYBALVI.

Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases):

Perform complete blood counts in patients with a history of a clinically significant low white blood cell (WBC) count or history of leukopenia or neutropenia. Discontinue LYBALVI if clinically significant decline in WBC occurs in the absence of other causative factors.

Dysphagia:

Use LYBALVI with caution in patients at risk for aspiration.

Seizures:

Use LYBALVI with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment:

Because LYBALVI may cause somnolence, and may impair judgment, thinking, or motor skills, caution patients about operating hazardous machinery, including motor vehicles, until they are certain that LYBALVI does not affect them adversely.

Body Temperature Dysregulation:

Use LYBALVI with caution in patients who may experience conditions that increase core body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Anticholinergic (Antimuscarinic) Effects:

Olanzapine, a component of LYBALVI, was associated with constipation, dry mouth, and tachycardia. Use LYBALVI with caution with other anticholinergic medications and in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus or related conditions. In postmarketing experience, the risk for severe adverse reactions (including fatalities) was increased with concomitant use of anticholinergic medications.

Hyperprolactinemia:

LYBALVI elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.

Risks Associated with Combination Treatment with Lithium or Valproate:

If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for a description of the risks for these products.

Interference with Laboratory Tests for Opioid Detection:

LYBALVI may cause false positive results with urinary immunoassay methods for detecting opioids. Use an alternative analytical technique (e.g., chromatographic methods) to confirm positive opioid urine drug screen results.

Most Common Adverse Reactions observed in clinical trials were:

  • Schizophrenia (LYBALVI): weight increased, somnolence, dry mouth, and headache
  • Bipolar I Disorder, Manic or Mixed Episodes (olanzapine): somnolence, dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite, and tremor
  • Bipolar I Disorder, Manic or Mixed Episodes, adjunct to lithium or valproate (olanzapine): dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia

Concomitant Medication:

LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. Concomitant use of LYBALVI is not recommended with strong CYP3A4 inducers, levodopa and dopamine agonists. Reduce dosage of LYBALVI when using with strong CYP1A2 inhibitors. Increase dosage of LYBALVI with CYP1A2 inducers. Use caution with diazepam, alcohol, other CNS acting drugs, or in patients receiving anticholinergic (antimuscarinic) medications. Monitor blood pressure and reduce dosage of antihypertensive drug in accordance with its approved product labeling.

Pregnancy:

May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with LYBALVI. Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LYBALVI during pregnancy.

Renal Impairment:

LYBALVI is not recommended for patients with end-stage renal disease (eGFR of <15 mL/minute/1.73 m2).

To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at 1-888-235-8008 or FDA at 1-800-FDA-1088 or https://www.fda.gov/medwatch.

Indications

LYBALVI is indicated for the treatment of:

  • Bipolar I disorder in adults
    • Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate
    • Maintenance monotherapy treatment
  • Schizophrenia in adults

Please see full Prescribing Information, including Boxed Warning, for LYBALVI.

For Healthcare Professionals

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