Mood disorders:
Indications for: LYBALVI
Acute treatment of manic or mixed episodes in bipolar I disorder as monotherapy or as adjunct to lithium or valproate. Maintenance monotherapy for bipolar I disorder.
Clinical Trials:
The approval of Lybalvi was based on data from 27 clinical studies, including the phase 3 ENLIGHTEN-1 (ClinicalTrials.gov Identifier: NCT02634346) and ENLIGHTEN-2 (ClinicalTrials.gov Identifier: NCT02694328) studies for the treatment of adults with schizophrenia.
In the ENLIGHTEN-1 study (N=403), the efficacy and safety of Lybalvi was evaluated in adults with acute exacerbation of schizophrenia. Patients were randomly assigned 1:1:1 to receive Lybalvi, olanzapine, or placebo once daily for 4 weeks.
Findings showed that treatment with Lybalvi led to statistically significant reductions from baseline in Positive and Negative Syndrome Scale scores compared with placebo (primary endpoint; P<.001) in patients experiencing an acute exacerbation of schizophrenia; a similar improvement was noted in the olanzapine arm when compared with placebo (P=.004).
The inclusion of samidorphan did not appear to negatively impact the antipsychotic efficacy of olanzapine.
The ENLIGHTEN-2 (N=561) study compared the weight gain profile of Lybalvi to olanzapine in adults with schizophrenia. Patients were randomly assigned 1:1 to receive Lybalvi or olanzapine for 24 weeks.
Results showed that treatment with Lybalvi was associated with statistically significant less weight gain compared with olanzapine (P=.003), and with a smaller proportion of patients who gained 10% or more of their baseline body weight (P=.003).
The approval of Lybalvi for the treatment of bipolar I disorder was supported by the established efficacy and safety profile of orally administered olanzapine in adequate and well-controlled studies.
Adult Dosage:
Monotherapy: initially 10mg/10mg or 15mg/10mg once daily. Adjust at intervals of at least 24hrs by increments/decrements of 5mg; max: 20mg/10mg once daily. Maintenance: 5mg/10mg, 10mg/10mg, 15mg/10mg, or 20mg/10mg once daily. Adjunctive to lithium/valproate: initially 10mg/10mg once daily. May adjust at weekly intervals of 5mg as tolerated; max: 20mg/10mg once daily. Patients with higher risk of hypotensive reactions, risk of slower olanzapine metabolism, or more sensitive to olanzapine: initially 5mg/10mg.
Children Dosage:
Not established.
LYBALVI Contraindications:
Current opioid use. Acute opioid withdrawal. If coadministered with lithium or valproate; refer to respective prescribing information.
Boxed Warning:
Increased mortality in elderly patients with dementia-related psychosis.
LYBALVI Warnings/Precautions:
Elderly with dementia-related psychosis (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Precipitation of severe opioid withdrawal in patients dependent on opioids; delay initiation for a minimum of 7 days after last use of short-acting opioids; or 14 days after last use of long-acting opioids. Risk of opioid overdose from attempts to overcome samidorphan blockade. Risk of resuming opioids in those with prior opioid use. Discontinue if neuroleptic malignant syndrome or if DRESS is suspected. Consider discontinuation if tardive dyskinesia occurs. Diabetes. Monitor for hyperglycemia, hyperlipidemia; do fasting blood glucose and lipids testing at beginning, and during therapy. Monitor for weight gain. Cardio- or cerebrovascular disease. Hypotension. Dehydration. Hypovolemia. Pre-existing low WBCs or history of leukopenia/neutropenia; monitor CBCs during 1st few months of treatment; discontinue if WBCs decline or severe neutropenia (ANC <1000/mm3) occurs. Perform fall risk assessments when initiating and recurrently on long-term therapy. Dysphagia. History of seizures. Conditions that lower the seizure threshold. Strenuous exercise. Exposure to extreme heat. Urinary retention. Significant prostatic hypertrophy. Constipation. History of paralytic ileus or related conditions. Breast cancer. Reevaluate periodically. Severe hepatic impairment. ESRD: not recommended. Neonates: risk of extrapyramidal and/or withdrawal symptoms post delivery (due to exposure during 3rd-trimester pregnancy). Pregnancy. Nursing mothers: monitor infants.
LYBALVI Classification:
Atypical antipsychotic + opioid antagonist.
LYBALVI Interactions:
See Contraindications. Concomitant strong CYP3A4 inducers, levodopa and dopamine agonists: not recommended. Concomitant strong CYP1A2 inhibitors: consider dosage reduction of olanzapine component. Concomitant CYP1A2 inducers: consider dosage increase of olanzapine component. Orthostatic hypotension with alcohol, diazepam, other CNS acting drugs, antihypertensives. Risk for severe GI adverse reactions with anticholinergic drugs; use cautiously.
Adverse Reactions:
Increased weight, somnolence, dry mouth, headache, asthenia, constipation, increased appetite, dizziness, tremor, dyspepsia, back pain, speech disorder, increased salivation, amnesia, paresthesia; orthostatic hypotension, syncope, agranulocytosis, hyperprolactinemia.
Drug Elimination:
Olanzapine: Half-life: 35-52 hours. Urine (unchanged): 7%; Urine (unchanged and metabolites): 57%; Feces (unchanged and metabolites): 30%
Samidorphan: Half-life: 7-11 hours. Urine (unchanged): 18%; Urine (unchanged and metabolites): 67%; Feces (unchanged and metabolites): 16%
Generic Drug Availability:
NO
How Supplied:
Tabs—7, 30, 90
Psychosis:
Indications for: LYBALVI
Schizophrenia.
Clinical Trials:
The approval of Lybalvi was based on data from 27 clinical studies, including the phase 3 ENLIGHTEN-1 (ClinicalTrials.gov Identifier: NCT02634346) and ENLIGHTEN-2 (ClinicalTrials.gov Identifier: NCT02694328) studies for the treatment of adults with schizophrenia.
In the ENLIGHTEN-1 study (N=403), the efficacy and safety of Lybalvi was evaluated in adults with acute exacerbation of schizophrenia. Patients were randomly assigned 1:1:1 to receive Lybalvi, olanzapine, or placebo once daily for 4 weeks.
Findings showed that treatment with Lybalvi led to statistically significant reductions from baseline in Positive and Negative Syndrome Scale scores compared with placebo (primary endpoint; P<.001) in patients experiencing an acute exacerbation of schizophrenia; a similar improvement was noted in the olanzapine arm when compared with placebo (P=.004).
The inclusion of samidorphan did not appear to negatively impact the antipsychotic efficacy of olanzapine.
The ENLIGHTEN-2 (N=561) study compared the weight gain profile of Lybalvi to olanzapine in adults with schizophrenia. Patients were randomly assigned 1:1 to receive Lybalvi or olanzapine for 24 weeks.
Results showed that treatment with Lybalvi was associated with statistically significant less weight gain compared with olanzapine (P=.003), and with a smaller proportion of patients who gained 10% or more of their baseline body weight (P=.003).
The approval of Lybalvi for the treatment of bipolar I disorder was supported by the established efficacy and safety profile of orally administered olanzapine in adequate and well-controlled studies.
Adult Dosage:
Initially 5mg/10mg or 10mg/10mg once daily. May adjust at weekly intervals of 5mg as tolerated; max: 20mg/10mg once daily. Patients with higher risk of hypotensive reactions, risk of slower olanzapine metabolism, or more sensitive to olanzapine: initially 5mg/10mg.
Children Dosage:
Not established.
LYBALVI Contraindications:
Current opioid use. Acute opioid withdrawal. If coadministered with lithium or valproate; refer to respective prescribing information.
Boxed Warning:
Increased mortality in elderly patients with dementia-related psychosis.
LYBALVI Warnings/Precautions:
Elderly with dementia-related psychosis (not approved use); increased risk of death or cerebrovascular events (eg, stroke, TIA). Precipitation of severe opioid withdrawal in patients dependent on opioids; delay initiation for a minimum of 7 days after last use of short-acting opioids; or 14 days after last use of long-acting opioids. Risk of opioid overdose from attempts to overcome samidorphan blockade. Risk of resuming opioids in those with prior opioid use. Discontinue if neuroleptic malignant syndrome or if DRESS is suspected. Consider discontinuation if tardive dyskinesia occurs. Diabetes. Monitor for hyperglycemia, hyperlipidemia; do fasting blood glucose and lipids testing at beginning, and during therapy. Monitor for weight gain. Cardio- or cerebrovascular disease. Hypotension. Dehydration. Hypovolemia. Pre-existing low WBCs or history of leukopenia/neutropenia; monitor CBCs during 1st few months of treatment; discontinue if WBCs decline or severe neutropenia (ANC <1000/mm3) occurs. Perform fall risk assessments when initiating and recurrently on long-term therapy. Dysphagia. History of seizures. Conditions that lower the seizure threshold. Strenuous exercise. Exposure to extreme heat. Urinary retention. Significant prostatic hypertrophy. Constipation. History of paralytic ileus or related conditions. Breast cancer. Reevaluate periodically. Severe hepatic impairment. ESRD: not recommended. Neonates: risk of extrapyramidal and/or withdrawal symptoms post delivery (due to exposure during 3rd-trimester pregnancy). Pregnancy. Nursing mothers: monitor infants.
LYBALVI Classification:
Atypical antipsychotic + opioid antagonist.
LYBALVI Interactions:
See Contraindications. Concomitant strong CYP3A4 inducers, levodopa and dopamine agonists: not recommended. Concomitant strong CYP1A2 inhibitors: consider dosage reduction of olanzapine component. Concomitant CYP1A2 inducers: consider dosage increase of olanzapine component. Orthostatic hypotension with alcohol, diazepam, other CNS acting drugs, antihypertensives. Risk for severe GI adverse reactions with anticholinergic drugs; use cautiously.
Adverse Reactions:
Increased weight, somnolence, dry mouth, headache, asthenia, constipation, increased appetite, dizziness, tremor, dyspepsia, back pain, speech disorder, increased salivation, amnesia, paresthesia; orthostatic hypotension, syncope, agranulocytosis, hyperprolactinemia.
Drug Elimination:
Olanzapine: Half-life: 35-52 hours. Urine (unchanged): 7%; Urine (unchanged and metabolites): 57%; Feces (unchanged and metabolites): 30%
Samidorphan: Half-life: 7-11 hours. Urine (unchanged): 18%; Urine (unchanged and metabolites): 67%; Feces (unchanged and metabolites): 16%
Generic Drug Availability:
NO
How Supplied:
Tabs—7, 30, 90
