Lybalvi

Increased Mortality, Cerebrovascular Adverse Reactions (Including Stroke) in Elderly Patients with Dementia-Related Psychosis

• Lybalvi is not approved for the treatment of dementia-related psychosis
• Antipsychotic use for dementia-related psychosis increases the risk of death in elderly patients, based on analyses from 17 placebo-controlled trials.
• Olanzapine linked to higher incidence of stroke and transient ischemic attack, including fatal stroke.

Precipitation of Severe Opioid Withdrawal in Patients Who Are Physiologically Dependent on Opioids

• Lybalvi is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal.
• Samidorphan can precipitate opioid withdrawal in patients who are dependent on opioids, which can lead to an opioid withdrawal syndrome, sometimes requiring hospitalization.
• Prior to initiating treatment, there should be an opioid-free interval:
  • At least 7 days from last use of short-acting opioids.
  • At least 14 days from last use of long-acting opioids.

Vulnerability to Life-Threatening Opioid Overdose

• Attempting to overcome Lybalvi’s opioid blockade with high or repeated doses of exogenous opioids could lead to life-threatening or fatal opioid intoxication, particularly if Lybalvi is interrupted or discontinued, subjecting the patient to high levels of unopposed opioid agonist as the samidorphan blockade wanes.
• If a Lybalvi-treated patient needs to treated with opioids for anesthesia or analgesia, Lybalvi should be discontinued; opioids should be administered by a person trained in the use of anesthetic drugs and the management of the respiratory effects of opioids; and the patient should be continuously monitored in a setting equipped and staffed for cardiopulmonary resuscitation.
• In non-emergency situations, if a patient treated with Lybalvi is expected to require opioid treatment, discontinue Lybalvi at least 5 days before opioid treatment and start olanzapine or another antipsychotic, if needed.
• Opioid treatment may be less effective or ineffective shortly after Lybalvi discontinuation.
• Patients with a history of chronic opioid use prior to treatment with Lybalvi may have decreased opioid tolerance if Lybalvi is interrupted or discontinued; this may increase the risk of opioid overdose if opioids are resumed at the previously tolerated dosage.

Neuroleptic Malignant Syndrome (NMS)

• Antipsychotic medications have been associated with NMS, a potentially fatal symptom complex.
• Clinical manifestations of NMS: Hyperpyrexia, muscle rigidity, delirium, autonomic instability.
• Additional signs of NMS: Elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), acute renal failure.
• Discontinue Lybalvi immediately if NMS is suspected.
• Intensive symptomatic treatment and monitoring should be provided to patients who develop NMS.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

• DRESS has been reported with olanzapine.
• May present with cutaneous reaction, eosinophilia, fever, and/or lymphadenopathy with systemic complications (eg, hepatitis, nephritis, pneumonitis, myocarditis, pericarditis)
• Discontinue Lybalvi if DRESS is suspected.

Metabolic Changes

• Hyperglycemia and Diabetes Mellitus
  • Hyperglycemia has been reported with atypical antipsychotics.
  • Monitor for symptoms of hyperglycemia during treatment.
  • Patients should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment.
• Dyslipidemia
  • Antipsychotics may cause adverse alterations in lipids.
  • Obtain fasting lipid profile at baseline and monitor periodically during treatment.
• Weight Gain
• • Antipsychotic use has been associated with weight gain.
  • Monitor weight at baseline and frequently thereafter.

Tardive Dyskinesia

• Patients treated with antipsychotics may develop tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements.
• Risk highest among elderly, especially elderly women.
• Tardive dyskinesia may develop after a brief treatment period, even at low doses, and may also occur after discontinuation of treatment.
• Prescribe Lybalvi in a manner that reduces the risk of tardive dyskinesia.
• Reserve chronic antipsychotic treatment for patients who suffer from chronic illness that is known to respond to antipsychotic drugs; and for whom alternative, effective, but potentially less harmful treatments are not available or appropriate.
• Use the lowest effective dose and the shortest duration of treatment to produce a satisfactory clinical response.
• Reassess the need for continued treatment and if signs/symptoms of tardive dyskinesia appear, consider discontinuing treatment with Lybalvi.
• Some patients may require continued treatment despite the presence of tardive dyskinesia.

Orthostatic Hypotension and Syncope

• Risk for orthostatic hypotension and syncope is greatest during initial dose administration.
• Patients vulnerable to hypotension: Orthostatic vital signs should be monitored.
• Lybalvi has not been evaluated in patients with a recent history of myocardial infarction or unstable cardiovascular disease.

Falls

• Lybalvi may cause somnolence, postural hypotension, and motor and sensory instability.
• Patients with diseases, conditions or on medications that exacerbate these effects: Complete fall risk assessments when initiating treatment and periodically during long term treatment.

Leukopenia, Neutropenia, and Agranulocytosis

• Leukopenia and neutropenia have been reported with Lybalvi.
• Risk factors for leukopenia, neutropenia: Pre-existing low white blood cell (WBC) count or absolute neutrophil count (ANC) and history of drug-induced leukopenia or neutropenia; perform CBC in these patients frequently during the first few months of treatment.
• Consider discontinuing Lybalvi at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
• Monitor patients with clinically significant neutropenia for fever, signs of infection; treat promptly.
• ANC< 1000/mm³: Discontinue Lybalvi.

Dysphagia

• Esophageal dysmotility and aspiration have been associated with antipsychotic drugs.
• Use cautiously in patients at risk for aspiration.

Seizures

• Lybalvi may cause seizures.
• The risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment

• Lybalvi may impair judgement, thinking and motor skills.
• Caution patients not to operate hazardous machinery, including motor vehicles, until they are reasonably certain that therapy does not affect them adversely.

Body Temperature Dysregulation

• Atypical antipsychotics may disrupt the body’s ability to reduce core body temperature.
• Use Lybalvi with caution in patients who perform strenuous exercise, are exposed to extreme heat, are dehydrated, or are on anticholinergic medications.

Anticholinergic Effects

• Use with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or a history of paralytic ileus or related conditions.
• Risk of severe adverse reactions was increased with concomitant anticholinergic medications.

Hyperprolactinemia

• Olanzapine may elevate prolactin levels; elevations may persist during chronic administration.
• Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.

Increased Mortality, Cerebrovascular Adverse Reactions (Including Stroke) in Elderly Patients with Dementia-Related Psychosis

• Lybalvi is not approved for the treatment of dementia-related psychosis
• Antipsychotic use for dementia-related psychosis increases the risk of death in elderly patients, based on analyses from 17 placebo-controlled trials.
• Olanzapine linked to higher incidence of stroke and transient ischemic attack, including fatal stroke.

Precipitation of Severe Opioid Withdrawal in Patients Who Are Physiologically Dependent on Opioids

• Lybalvi is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal.
• Samidorphan can precipitate opioid withdrawal in patients who are dependent on opioids, which can lead to an opioid withdrawal syndrome, sometimes requiring hospitalization.
• Prior to initiating treatment, there should be an opioid-free interval:
  • At least 7 days from last use of short-acting opioids.
  • At least 14 days from last use of long-acting opioids.

Vulnerability to Life-Threatening Opioid Overdose

• Attempting to overcome Lybalvi’s opioid blockade with high or repeated doses of exogenous opioids could lead to life-threatening or fatal opioid intoxication, particularly if Lybalvi is interrupted or discontinued, subjecting the patient to high levels of unopposed opioid agonist as the samidorphan blockade wanes.
• If a Lybalvi-treated patient needs to treated with opioids for anesthesia or analgesia, Lybalvi should be discontinued; opioids should be administered by a person trained in the use of anesthetic drugs and the management of the respiratory effects of opioids; and the patient should be continuously monitored in a setting equipped and staffed for cardiopulmonary resuscitation.
• In non-emergency situations, if a patient treated with Lybalvi is expected to require opioid treatment, discontinue Lybalvi at least 5 days before opioid treatment and start olanzapine or another antipsychotic, if needed.
• Opioid treatment may be less effective or ineffective shortly after Lybalvi discontinuation.
• Patients with a history of chronic opioid use prior to treatment with Lybalvi may have decreased opioid tolerance if Lybalvi is interrupted or discontinued; this may increase the risk of opioid overdose if opioids are resumed at the previously tolerated dosage.

Neuroleptic Malignant Syndrome (NMS)

• Antipsychotic medications have been associated with NMS, a potentially fatal symptom complex.
• Clinical manifestations of NMS: Hyperpyrexia, muscle rigidity, delirium, autonomic instability.
• Additional signs of NMS: Elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), acute renal failure.
• Discontinue Lybalvi immediately if NMS is suspected.
• Intensive symptomatic treatment and monitoring should be provided to patients who develop NMS.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

• DRESS has been reported with olanzapine.
• May present with cutaneous reaction, eosinophilia, fever, and/or lymphadenopathy with systemic complications (eg, hepatitis, nephritis, pneumonitis, myocarditis, pericarditis)
• Discontinue Lybalvi if DRESS is suspected.

Metabolic Changes

• Hyperglycemia and Diabetes Mellitus
  • Hyperglycemia has been reported with atypical antipsychotics.
  • Monitor for symptoms of hyperglycemia during treatment.
  • Patients should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment.
• Dyslipidemia
  • Antipsychotics may cause adverse alterations in lipids.
  • Obtain fasting lipid profile at baseline and monitor periodically during treatment.
• Weight Gain
• • Antipsychotic use has been associated with weight gain.
  • Monitor weight at baseline and frequently thereafter.

Tardive Dyskinesia

• Patients treated with antipsychotics may develop tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements.
• Risk highest among elderly, especially elderly women.
• Tardive dyskinesia may develop after a brief treatment period, even at low doses, and may also occur after discontinuation of treatment.
• Prescribe Lybalvi in a manner that reduces the risk of tardive dyskinesia.
• Reserve chronic antipsychotic treatment for patients who suffer from chronic illness that is known to respond to antipsychotic drugs; and for whom alternative, effective, but potentially less harmful treatments are not available or appropriate.
• Use the lowest effective dose and the shortest duration of treatment to produce a satisfactory clinical response.
• Reassess the need for continued treatment and if signs/symptoms of tardive dyskinesia appear, consider discontinuing treatment with Lybalvi.
• Some patients may require continued treatment despite the presence of tardive dyskinesia.

Orthostatic Hypotension and Syncope

• Risk for orthostatic hypotension and syncope is greatest during initial dose administration.
• Patients vulnerable to hypotension: Orthostatic vital signs should be monitored.
• Lybalvi has not been evaluated in patients with a recent history of myocardial infarction or unstable cardiovascular disease.

Falls

• Lybalvi may cause somnolence, postural hypotension, and motor and sensory instability.
• Patients with diseases, conditions or on medications that exacerbate these effects: Complete fall risk assessments when initiating treatment and periodically during long term treatment.

Leukopenia, Neutropenia, and Agranulocytosis

• Leukopenia and neutropenia have been reported with Lybalvi.
• Risk factors for leukopenia, neutropenia: Pre-existing low white blood cell (WBC) count or absolute neutrophil count (ANC) and history of drug-induced leukopenia or neutropenia; perform CBC in these patients frequently during the first few months of treatment.
• Consider discontinuing Lybalvi at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
• Monitor patients with clinically significant neutropenia for fever, signs of infection; treat promptly.
• ANC< 1000/mm³: Discontinue Lybalvi.

Dysphagia

• Esophageal dysmotility and aspiration have been associated with antipsychotic drugs.
• Use cautiously in patients at risk for aspiration.

Seizures

• Lybalvi may cause seizures.
• The risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment

• Lybalvi may impair judgement, thinking and motor skills.
• Caution patients not to operate hazardous machinery, including motor vehicles, until they are reasonably certain that therapy does not affect them adversely.

Body Temperature Dysregulation

• Atypical antipsychotics may disrupt the body’s ability to reduce core body temperature.
• Use Lybalvi with caution in patients who perform strenuous exercise, are exposed to extreme heat, are dehydrated, or are on anticholinergic medications.

Anticholinergic Effects

• Use with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or a history of paralytic ileus or related conditions.
• Risk of severe adverse reactions was increased with concomitant anticholinergic medications.

Hyperprolactinemia

• Olanzapine may elevate prolactin levels; elevations may persist during chronic administration.
• Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.