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LYBALVI (olanzapine and samidorphan)
What is LYBALVI?
- LYBALVI is a combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist
- The mechanism of action of olanzapine is unclear, however, its efficacy in the treatment of schizophrenia or bipolar I disorder could be mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism
- The mechanism of action of samidorphan could be mediated through opioid receptor antagonism
What is LYBALVI indicated for?
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
Please see Important Safety Information and full Prescribing Information, including Boxed Warning.
What is the boxed warning for LYBALVI?
The Boxed Warning for LYBALVI is as follows:
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LYBALVI is not approved for the treatment of patients with dementia-related psychosis.
Please see Important Safety Information and full Prescribing Information, including Boxed Warning.
What are the contraindications for LYBALVI?
LYBALVI is contraindicated in patients:
- who are using opioids
- who 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.
Since olanzapine is one of the components of LYBALVI, are they indicated to treat the same conditions?
- LYBALVI is a combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist
- LYBALVI does not have all the same indications as olanzapine
- LYBALVI is indicated for the treatment of schizophrenia in adults
-
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
Please see Important Safety Information and full Prescribing Information, including Boxed Warning.
Do drug interactions need to be considered when prescribing LYBALVI?
- Yes. LYBALVI is contraindicated in patients who are taking opioids or are undergoing acute opioid withdrawal. Concomitant use is not recommended with strong CYP3A4 inducers, levodopa, or dopamine agonists. Use caution with diazepam, alcohol, or other CNS-acting drugs, as well as with medications having anticholinergic (antimuscarinic) effects. Consider reducing dosage of the olanzapine component of LYBALVI when used with strong CYP1A2 inhibitors. Consider increasing the dosage of the olanzapine component of LYBALVI with CYP1A2 inducers. Monitor blood pressure and reduce dosage of antihypertensive drug in accordance with its approved product labeling
WEIGHT GAIN
How much weight did patients with schizophrenia gain on average in LYBALVI clinical trials?
- In the 24-week trial evaluating weight changes for patients taking LYBALVI vs olanzapine, patients treated with LYBALVI gained on average 4.2% of baseline body weight and those taking olanzapine gained 6.6%
- In the 4-week, placebo-controlled trial of adult patients with schizophrenia, mean changes in weight were 3.0 kg (6.6 lbs) in patients treated with LYBALVI, 2.4 kg (5.3 lbs) in patients treated with olanzapine, and 0.2 kg (0.4 lbs) in patients treated with placebo. This study evaluated antipsychotic efficacy and safety of LYBALVI vs placebo and was not designed to assess or compare the weight effects of LYBALVI vs olanzapine
DOSING AND ADMINISTRATION
What are the dosage and administration recommendations for LYBALVI?
- Administer LYBALVI orally once daily, with or without food, as a single tablet
- Do not divide tablets or combine strengths
LYBALVI Initiation In Patients Using Opioids
- LYBALVI is contraindicated in patients using opioids or undergoing acute opioid withdrawal
- In patients who use opioids, delay initiation of LYBALVI for a minimum of 7 days after last use of short-acting opioids and 14 days after last use of long-acting opioids
Recommended Dosage in Schizophrenia
- Initiate LYBALVI at 5 mg/10 mg (contains 5 mg of olanzapine and 10 mg of samidorphan) or 10 mg/10 mg (contains 10 mg of olanzapine and 10 mg of samidorphan) orally once daily. The recommended dosage is 10 mg/10 mg, 15 mg/10 mg (contains 15 mg of olanzapine and 10 mg of samidorphan), or 20 mg/10 mg (contains 20 mg of olanzapine and 10 mg of samidorphan) once daily
- Dosage may be adjusted at weekly intervals of 5 mg (based on the olanzapine component of LYBALVI) depending upon clinical response and tolerability, up to a maximum recommended dosage of 20 mg/10 mg once daily
Recommended Dosage in Bipolar I Disorder (Manic or Mixed Episodes)
-
Monotherapy: Initiate LYBALVI at 10 mg/10 mg or 15 mg/10 mg once daily. The recommended dosage is 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg once daily. The maximum recommended dosage is 20 mg/10 mg once daily
- Dosage adjustments should occur at intervals of not less than 24 hours. When dosage adjustments are necessary, dose increments/decrements of 5 mg (based on the olanzapine component of LYBALVI) are recommended
- Maintenance monotherapy: Administer LYBALVI at 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, or 20 mg/10 mg once daily
-
Adjunctive to lithium or valproate: Initiate LYBALVI at 10 mg/10 mg once daily. The recommended dosage is 10 mg/10 mg, 15 mg/10 mg or 20 mg/10 mg, once daily
- Dosage may be adjusted at weekly intervals of 5 mg (based on the olanzapine component of LYBALVI), depending upon clinical response and tolerability, up to the maximum recommended dosage of 20 mg/10 mg once daily
Dosage Recommendations in Specific Populations
- The recommended starting dosage of LYBALVI is 5 mg/10 mg once daily in patients who have a higher risk of hypotensive reactions, are at risk of slower olanzapine metabolism, or may be more pharmacodynamically sensitive to olanzapine
- If dose escalation is necessary, increase the dosage slowly in these patients
Can patients split LYBALVI tablets in half?
- Do not divide tablets or combine strengths
MECHANISM OF ACTION
What is the mechanism of action (MOA) for LYBALVI in bipolar I disorder and schizophrenia?
LYBALVI is a combination of olanzapine, an atypical antipsychotic, and samidorphan (as samidorphan L-malate), an opioid antagonist.
- The mechanism of action of olanzapine is unclear, however, its efficacy in the treatment of schizophrenia or bipolar I disorder could be mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism
- The mechanism of action of samidorphan could be mediated through opioid receptor antagonism
LYBALVI CLINICAL DATA
What is the efficacy data for LYBALVI in the treatment of schizophrenia?
ENLIGHTEN-1
- Evaluated the efficacy and safety of LYBALVI in schizophrenia
ENLIGHTEN-1 efficacy and safety data
ENLIGHTEN-2
- Evaluated safety and changes in body weight with LYBALVI relative to olanzapine in schizophrenia
What is the Positive and Negative Syndrome Scale (PANSS) that was used in the ENLIGHTEN-1 study in adults with schizophrenia?
- The PANSS is a 30-item scale that is used to measure and assess the severity of positive and negative symptoms of schizophrenia, and general psychopathology, each rated on a scale of 1 (absent) to 7 (extreme)
- Total PANSS scores range from 30 to 210, with a higher score reflecting greater symptom severity1
- Symptoms of schizophrenia measured by the PANSS include2
- Positive symptoms (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness, hostility)
- Negative symptoms (blunted affect, emotional withdrawal, poor rapport, passive-apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking)
- General psychopathology (somatic concern, anxiety, guilt feeling, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgement and insight, disturbance of volition, poor impulse control, preoccupation, active social avoidance)
What is the basis for the approval of LYBALVI in bipolar I disorder?
- There are no clinical data with LYBALVI in patients with bipolar I disorder
- The efficacy of LYBALVI in the treatment of adult patients with bipolar I disorder has been established based on adequate and well-controlled studies of orally-administered olanzapine
What is the Young Mania Rating Scale (Y-MRS) that was used in the studies of olanzapine in adults with bipolar I disorder?
- The Y-MRS is one of the most frequently used rating scales to assess manic symptoms3
- The Y-MRS is traditionally used to assess the degree of manic symptomatology in a range from 0 (no manic features) to 60 (maximum score)1
- The Y-MRS combines severity scores from the following symptoms4
- Elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, speech, language-disordered thoughts, thought content (grandiosity, paranoia, delusions, or hallucinations), disruptive or aggressive behavior, appearance, insight into mental illness
What are the common adverse reactions associated with the use of LYBALVI?
Most common adverse reactions (incidence ≥5% and at least twice that of placebo) were:
- Schizophrenia: weight increased, somnolence, dry mouth, and headache
The safety of LYBALVI for treatment of bipolar I disorder relies on olanzapine studies. In trials of olanzapine in bipolar I disorder, the most common adverse reactions (incidence of ≥5% of patients exposed to olanzapine and ≥2x placebo) were:
- 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, and paresthesia
For a complete list of adverse reactions, please refer to the full Prescribing Information for LYBALVI.
Reference: LYBALVI [prescribing information]. Waltham, MA: Alkermes, Inc.; 2021.