LYBALVI is indicated for the treatment of: Schizophrenia in adults Bipolar I disorder in adults Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate Maintenance monotherapy treatment LYBALVI is a combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist, indicated for the treatment of: Schizophrenia in adults ( 1 ) Bipolar I disorder in adults ( 1 ) Acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate Maintenance monotherapy treatment
Contraindications
LYBALVI is contraindicated in patients: who are using opioids [ see Warnings and Precautions ( 5.3 , 5.4 ), Drug Interactions ( 7.3 )] . who are undergoing acute opioid withdrawal [see Warnings and Precautions ( 5.3 , 5.4 ), Drug Interactions ( 7.3 )] . If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for these products [see Warnings and Precautions ( 5.18 )] .
Patients using opioids. ( 4 ) Patients undergoing acute opioid withdrawal. ( 4 ) If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for those products. ( 4 )
Warnings and precautions
Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis : Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities). ( 5.2 ) Precipitation of Opioid Withdrawal in Patients Who are Dependent on Opioids : LYBALVI can precipitate 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 to avoid precipitation of opioid withdrawal.
( 2.1 , 5.3 ) Vulnerability to Life-Threatening Opioid Overdose : Risk of Opioid Overdose from Attempts to Overcome LYBALVI Opioid Blockade: Attempts to overcome LYBALVI opioid blockade with high or repeated doses of opioids may lead to fatal opioid intoxication, particularly if LYBALVI therapy is interrupted or discontinued. ( 5.4 ) Risk of Resuming Opioids in Patients with Prior Opioid Use : Patients with a history of chronic opioid use prior to LYBALVI treatment may have decreased opioid tolerance if LYBALVI therapy is interrupted or discontinued.
( 5.4 ) Neuroleptic Malignant Syndrome : Manage with immediate discontinuation and close monitoring. ( 5.5 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) : Discontinue if DRESS is suspected. ( 5.6 ) Metabolic Changes : Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. ( 5.7 ) Tardive Dyskinesia : Discontinue if clinically appropriate. ( 5.8 ) Orthostatic Hypotension and Syncope : Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope.
( 5.9 ) Leukopenia, Neutropenia, and Agranulocytosis : Perform complete blood counts in patients with a history of a clinically significant low white blood cell (WBC) count. Consider discontinuation if clinically significant decline in WBC in the absence of other causative factors. ( 5.11 ) Seizures : Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. ( 5.13 ) Potential for Cognitive and Motor Impairment : Use caution when operating machinery.
( 5.14 ) Anticholinergic (Antimuscarinic) Effects: Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus or related conditions. ( 5.16 ) Hyperprolactinemia : May elevate prolactin levels. ( 5.17 )
5.1Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. In placebo-controlled clinical trials of elderly patients with dementia-related psychosis, the incidence of death in olanzapine-treated patients was significantly greater than in placebo-treated patients (3.5% vs 1.5%, respectively). Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients.
Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. LYBALVI is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.2 )].
5.2Cerebrovascular Adverse Reactions, Including Stroke in Elderly Patients with Dementia-Related Psychosis
Cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in trials of olanzapine in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse reactions in patients treated with olanzapine compared to patients treated with placebo. LYBALVI is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.1 )] .
5.3 Precipitation of Severe Opioid Withdrawal in Patients Who Are Physiologically Dependent on Opioids Samidorphan, an opioid antagonist that is a component of LYBALVI, can precipitate opioid withdrawal in patients who are dependent on opioids, which can lead to an opioid withdrawal syndrome, sometimes requiring hospitalization. Therefore, 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 [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7.3 )] .
5.4 Vulnerability to Life-Threatening Opioid Overdose Risk of Opioid Overdose from Attempts to Overcome Samidorphan Blockade LYBALVI contains samidorphan, an opioid antagonist. Attempting to overcome LYBALVI's opioid blockade with high or repeated doses of exogenous opioids (e.g., because of ineffective analgesia or opioid withdrawal symptoms) could lead to life-threatening or fatal opioid intoxication (e.g., respiratory arrest, circulatory collapse), 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 individual(s) trained in the use of anesthetic drugs and the management of the respiratory effects of opioids, specifically the establishment and maintenance of a patent airway and assisted ventilation, and Appropriately trained personnel should continuously monitor the patient in a setting equipped and staffed for cardiopulmonary resuscitation.
For recommendations on starting opioids in LYBALVI-treated patients in non-emergent situations, see Drug Interactions ( 7.3 ). Risk of Resuming Opioids in Patients with Prior Opioid Use 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.
a potentially fatal symptom complex, has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue LYBALVI and provide intensive symptomatic treatment and monitoring.
5.6 Drug Reaction with Eosinophilia and Systemic Symptoms Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported with exposure to olanzapine, a component of LYBALVI [see Adverse Reactions ( 6.2 )] . DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis,
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Interactions
Strong CYP3A4 Inducers : Not recommended. ( 7.1 ) Strong CYP1A2 Inhibitors : Consider dosage reduction of olanzapine component of LYBALVI. ( 7.1 ) CYP1A2 Inducer : Consider dosage increase of the olanzapine component of LYBALVI. ( 7.1 ) CNS Acting Drugs : May potentiate orthostatic hypotension. ( 7.1 ) Anticholinergic Drugs: Can increase risk for severe gastrointestinal adverse reactions. ( 7.1 ) Antihypertensive Agents : Monitor blood pressure.
( 7.2 ) Levodopa and Dopamine Agonists : Not recommended. ( 7.2 )
7.1Effects 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 AUC inf of olanzapine and samidorphan [see Clinical Pharmacology ( 12.3 )], 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 C max [see Clinical Pharmacology ( 12.3 )] , 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 ( 12.3 )] , 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 ( 5.9 )] . 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 ( 5.16 )] .
7.2Effects 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.
7.3Opioids
LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal [see Contraindications ( 4 )]. 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 ( 2.1 ), Warnings and Precautions ( 5.3 )] .
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 ( 5.4 )]. 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.
7.4Interference with Laboratory Tests Interference with Laboratory Tests for Opioid Detection Because
LYBALVI contains samidorphan, an opioid antagonist, LYBALVI may be cross-reactive with urinary immunoassay methods used for detecting opioids, resulting in false positive results. Use an alternative analytical technique (e.g., chromatographic methods) to confirm positive opioid urine drug screen results [see Contraindications ( 4 ) and Warnings and Precautions ( 5.19 )] .
Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including LYBALVI, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/ . Risk Summary 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 (see Clinical Considerations ) .
Overall published epidemiologic studies of pregnant women exposed to olanzapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data ) . There are no available data on the use of samidorphan or the combination of olanzapine and samidorphan in pregnant women to determine a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including LYBALVI, during pregnancy (see Clinical Considerations ) . LYBALVI In an animal reproduction study, oral administration of olanzapine and samidorphan to pregnant rats during the period of organogenesis produced adverse effects on embryofetal development and fetal toxicity at maternally toxic doses that are 6 times and >400 times the maximum recommended human dose (MRHD) of 20 mg/10 mg olanzapine/samidorphan in LYBALVI, respectively based on AUC.
There were no adverse effects on embryofetal development at doses of olanzapine and samidorphan that are approximately 1 and 80 times, respectively, the MRHD based on AUC (see Data ) . Olanzapine In animal reproduction studies, there was no evidence of malformations in rats or rabbits when orally administered olanzapine at doses up to 9 and 30 times the MRHD dose (20 mg) based on mg/m 2 body surface area, respectively.
In an oral rat embryofetal developmental toxicity study, early resorptions and increased numbers of nonviable fetuses were observed at a dose 9 times the MRHD based on mg/m 2 body surface area and gestation was prolonged at 5 times the MRHD based on mg/m 2 body surface area. In an oral rabbit embryofetal developmental toxicity study, fetal toxicity (manifested as increased resorptions and decreased fetal weight) occurred at a maternally toxic dose of olanzapine which is 30 times the MRHD based on mg/m 2 body surface area (see Data ) .
Samidorphan In animal reproduction studies, oral administration of samidorphan to pregnant rats and rabbits during the period of organogenesis caused fetal toxicities in rats only at maternally toxic doses that are >248 times the human exposure at the MRHD of 10 mg/day based on AUC. Oral administration of samidorphan to pregnant rats during pregnancy and lactation resulted in lower pup survival and decreased pup weights at 188 times the human exposure at the MRHD based on AUC (see Data ) .
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryofetal Risk There is risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization and suicide.
Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/ Neonatal Risks Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including the olanzapine component of LYBALVI, during the third trimester of pregnancy.
These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects.
A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. Animal Data LYBALVI Olanzapine and samidorphan were orally administered to pregnant rats during the period of organogenesis at doses of 0.5/10, 2/50, 6/200, and 0/200 mg/kg/day (olanzapine/samidorphan) which are approximately <1/10 times to 6/448 times the MRHD of 20 mg/10 mg, olanzapine/samidorphan, respectively, based on AUC.
Maternal toxicity consisting of decreased body weight and food consumption was observed at all dose levels. Administration of samidorphan alone (200 mg/kg/day) and 6/200 mg/kg/day olanzapine/samidorphan decreased mean fetal body weights, increased litter incidence of bent ribs and bent scapula; however, the incidence of bent scapula and bent ribs was not increased when samidorphan was administered in combination with olanzapine compared to the incidence with samidorphan alone.
Administration of olanzapine/samidorphan at 6/200 mg/kg/day also increased resorptions and post-implantation loss, with correlating lower mean viable fetuses and litter size. The no observed adverse effect level (NOAEL) for embryofetal development is 2/50 mg/kg/day, which is approximately 1/80 times the MRHD of 20 mg/10 mg olanzapine/samidorphan respectively, based on AUC. Olanzapine Olanzapine was orally administered to pregnant rats and rabbits during the period of organogenesis at doses up to 18 mg/kg/day in rats and at doses up to 30 mg/kg/day in rabbits (9 times and 30 times the MRHD of 20 mg/day based on mg/m 2 body surface area, respectively), and no evidence of malformations was observed.
In an oral rat embryofetal developmental toxicity study, early resorptions and increased numbers of nonviable fetuses were observed at a dose of 18 mg/kg/day (9 times the MRHD based on mg/m 2 body surface area). Gestation was prolonged at 10 mg/kg/day (5 times the MRHD based on mg/m 2 body surface area). In an oral rabbit embryofetal developmental toxicity study, fetal toxicity (manifested as increased resorptions and decreased fetal weight) occurred at a maternally toxic dose of olanzapine at 30 mg/kg/day (30 times the MRHD based on mg/m 2 body surface area).
Samidorphan Samidorphan was orally administered to pregnant rats during the period of organogenesis at doses of 25, 100, and 300 mg/kg/day, which are approximately 29 to 742 times the MRHD of 10 mg/day based on AUC. Samidorphan was associated with an increased incidence of skeletal variations (unossified sternebrae and bent ribs) at maternally toxic doses of ≥100 mg/kg/day, and skeletal malformations (bent or misshapen forelimbs, hindlimbs, and/or scapula) at 300 mg/kg/day which are >248 and 742 times the MRHD based on AUC, respectively.
The NOAEL for embryofetal development is 25 mg/kg/day, which is approximately 29 times the MRHD based on AUC. Samidorphan did not cause adverse effects on embryofetal development when orally administered to pregnant rabbits during the period of organogenesis at doses of 10, 30, and 90 mg/kg/day, which are up to approximately 143 times the MRHD based on AUC. Samidorphan was orally administered to pregnan
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Adverse reactions
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 ( 5.1 )] Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions ( 5.2 )] Precipitation of Opioid Withdrawal in Patients Who Are Dependent on Opioids [see Warnings and Precautions ( 5.3 ) ] Vulnerability to Life-Threatening Opioid Overdose [see Warnings and Precautions ( 5.4 )] Neuroleptic Malignant Syndrome [see Warnings and Precautions ( 5.5 )] Drug Reaction with Eosinophilia and Systemic Symptoms [see Warnings and Precautions ( 5.6 )] Metabolic Changes [see Warnings and Precautions ( 5.7 )] Tardive Dyskinesia [see Warnings and Precautions ( 5.8 )] Orthostatic Hypotension and Syncope [see Warnings and Precautions ( 5.9 )] Falls [see Warnings and Precautions ( 5.10 )] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions ( 5.11 )] Dysphagia [see Warnings and Precautions ( 5.12 )] Seizures [see Warnings and Precautions ( 5.13 )] Potential for Cognitive and Motor Impairment [see Warnings and Precautions ( 5.14 )] Body Temperature Regulation [see Warnings and Precautions ( 5.15 )] Anticholinergic (Antimuscarinic) Effects [see Warnings and Precautions ( 5.16 )] Hyperprolactinemia [see Warnings and Precautions ( 5.17 )] Risks Associated with Combination Treatment with Lithium or Valproate [see Warnings and Precautions ( 5.18 )] Most common adverse reactions (incidence ≥5% and at least twice placebo): Schizophrenia (LYBALVI): weight increased, somnolence, dry mouth, and headache.
( 6.1 ) Bipolar I Disorder, Manic or Mixed Episodes (olanzapine): somnolence, dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite, tremor. ( 6.1 ) 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at 1-888-235-8008 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 15.0 mg/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 * 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.
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) 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 w
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Composition
Active ingredients
OLANZAPINE 10MG; SAMIDORPHAN L-MALATE EQ 10MG BASE
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
