Olanzapine-Samidorphan

Olanzapine-Samidorphan is a combination medication used to treat schizophrenia and bipolar I disorder in adults.

• Olanzapine-Samidorphan is available under the following different brand names: Lybalvi

Adult dosage

Tablet

• 5mg/10mg
• 10mg/10mg
• 15mg/10mg
• 20mg/10mg

Schizophrenia

Adult dosage

• Initial dose: Olanzapine 5 mg/samidorphan 10 mg OR olanzapine 10 mg/samidorphan 10 mg orally once daily
• Maintenance dose: May adjust dosage at weekly intervals of 5 mg (based on the olanzapine component) depending on clinical response and tolerability; not to exceed olanzapine 20 mg/samidorphan 10 mg once daily

Bipolar I Disorder

Adult dosage

• Adjunctive to lithium or valproate
• Initial dose: 1 tablet (olanzapine 10 mg/samidorphan 10 mg) orally once daily
• Maintenance dose: May adjust dosage at weekly intervals of 5 mg (based on the olanzapine component) depending on clinical response and tolerability; not to exceed olanzapine 20 mg/samidorphan 10 mg once daily

Monotherapy

• Initial dose: Olanzapine 10 mg/samidorphan 10 mg OR olanzapine 15mg/samidorphan 10 mg orally once daily
• Adjust dose in increments/decrements of 5 mg (based on olanzapine component), if necessary, at intervals of more than 24 hours; not to exceed olanzapine 20 mg/samidorphan 10 mg once daily
• Maintenance monotherapy: Not to exceed olanzapine 20 mg/samidorphan 10 mg once daily

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Olanzapine-Samidorphan include:

• weight gain,
• drowsiness,
• dry mouth,
• headache,
• weakness/lethargy,
• constipation,
• increased appetite,
• dizziness,
• tremor,
• heartburn/indigestion,
• back pain,
• speech disorder,
• increased salivation,
• amnesia, and
• numbness and tingling (paresthesia).

Serious side effects of Olanzapine-Samidorphan include:

• high blood sugar (hyperglycemia) and diabetes: feel very thirsty, need to urinate more than usual, feel very hungry, feel weak or tired, feel sick to the stomach, feel confused, or breath smells fruity,
• increased fat levels (cholesterol and triglycerides) in the blood,
• weight gain.
• uncontrolled body movements (tardive dyskinesia), 
• decreased blood pressure (orthostatic hypotension) and fainting,
• low white blood cell count,
• difficulty swallowing,
• seizures (convulsions),
• problems controlling body temperature,
• increased prolactin levels in the blood,
• sleepy or dizzy, may cause a decrease in blood pressure when changing position (orthostatic hypotension),
• falls that can cause fractures or other injuries,
• stroke (cerebrovascular problems) in elderly people with dementia-related psychosis,
• neuroleptic malignant syndrome (NMS): high fever, sweating, stiff muscles, changes in breathing, pulse, heart rate, and blood pressure, confusion, and 
• drug reaction with eosinophilia and systemic symptoms (DRESS): rash, fever, swollen glands, kidney, liver, lung, and heart problems.

Rare side effects of Olanzapine-Samidorphan include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Olanzapine-Samidorphan has severe interactions with the following drug:
  • amisulpride
• Olanzapine-Samidorphan has serious interactions with at least 40 other drugs.
• Olanzapine-Samidorphan has moderate interactions with at least 351 other drugs.
• Olanzapine-Samidorphan has minor interactions with the following drugs: 
  • brimonidine
  • chasteberry
  • ethanol
  • eucalyptus
  • omeprazole
  • ruxolitinib
  • ruxolitinib topical
  • sage

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Patients using opioids
• Patients undergoing acute opioid withdrawal
• If administered with lithium or valproate, refer to lithium or valproate prescribing information for contraindications for these products

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Olanzapine-Samidorphan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Olanzapine-Samidorphan?”

Cautions

• A significantly greater increase in death was reported in elderly patients with dementia-related psychosis treated with olanzapine; the majority of deaths were either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia)
• Cerebrovascular adverse reactions (eg, stroke, transient ischemic attack), including fatalities, were reported in olanzapine trials in elderly patients with dementia-related psychosis
• DRESS reported with exposure to olanzapine; may present with a cutaneous reaction (eg, rash, exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications (eg, hepatitis, nephritis, pneumonitis, myocarditis, pericarditis); discontinue treatment if DRESS is suspected
• Antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls, fractures, or other injuries; complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy
• Olanzapine was associated with constipation, dry mouth, tachycardia, and all adverse reactions related to cholinergic antagonism; 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 condition
• Atypical antipsychotics may disrupt the ability to reduce core body temperature; strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use with caution in patients who may experience these conditions
• May cause somnolence and has the potential to impair judgment, thinking, or motor skills; advise patients to exercise caution when operating hazardous machinery, including motor vehicles
• May cause seizures; use caution in patients with a history of seizures or with conditions that lower the seizure threshold
• Esophageal dysmotility and aspiration have been associated with antipsychotic drug use; use with caution in patients at risk for aspiration
• Refer to lithium or valproate prescribing information for a description of the risks for these products if used
• Hyperprolactinemia
  • Olanzapine elevates prolactin levels and elevation can persist during long-term administration
  • Hyperprolactinemia may suppress hypothalamic gonadotropin-releasing hormone, resulting in reduced pituitary gonadotropin secretion; may inhibit reproductive function by impairing gonadal steroidogenesis in both females and males
  • Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported
  • Long-standing hyperprolactinemia, when associated with hypogonadism, may lead to decreased bone density in both females and males
• Tardive dyskinesia
  • Tardive dyskinesia may develop in patients treated with antipsychotic drugs; elderly patients appear to be at the highest risk
  • Prescribe in a manner that is most likely to reduce the risk of tardive dyskinesia.
  • Reserve long-term antipsychotic treatment for patients:
    • Who has a chronic illness that is responsive to antipsychotic drugs
    • For whom alternative, effective, but potentially less harmful treatments are unavailable or inappropriate
  • If long-term treatment is necessary, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response; periodically reassess the need to continue treatment
  • If signs and symptoms of tardive dyskinesia appear, consider discontinuation
• Opioids
  • Contraindicated
  • Olanzapine-Samidorphan increases the risk of precipitation of acute opioid withdrawal in opioid-dependent patients
  • Emergencies: If the treated patient requires opioid treatment for anesthesia or analgesia, discontinue Olanzapine-Samidorphan; opioids should be administered by properly trained individual(s), and properly monitor the patient in a setting equipped and staffed for cardiopulmonary resuscitation
  • Nonemergency situations: If the treated patient is expected to require opioid treatment (eg, for analgesia during or after an elective surgical procedure), discontinue Olanzapine-Samidorphan at least 5 days before opioid treatment and start olanzapine or another antipsychotic, if needed
  • Samidorphan is an opioid antagonist; opioid treatment may be less effective or ineffective shortly after discontinuing Olanzapine-Samidorphan
  • Explain the risks associated with precipitated withdrawal and the importance of giving an accurate account of last opioid use to patients and caregivers
  • Patients with a history of long-term opioid use before treatment with Olanzapine-Samidorphan have decreased opioid tolerance if therapy is interrupted or discontinued
  • Advise that decreased tolerance may increase the risk of an opioid overdose if opioids are resumed at the previously tolerated dosage
• Neuroleptic malignant syndrome (NMS)
  • NMS is reported in association with the 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 therapy, provide intensive symptomatic treatment, and monitor
• Metabolic changes
  • Atypical antipsychotic drugs have been associated with metabolic changes that include 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
  • Monitor for symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness
  • Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose (FBG) testing
  • Hyperglycemia may resolve once the atypical antipsychotic is discontinued; however, some patients required antidiabetic treatment despite discontinuation
  • Test FBG and fasting lipid profile at the beginning of treatment and periodically during treatment
  • Monitor weight before initiation and frequently thereafter
  • Leukopenia, neutropenia, and agranulocytosis
  • Leukopenia and neutropenia were reported during treatment
  • Agranulocytosis (including fatal cases) has been reported with other agents in this class
  • Possible risk factors for leukopenia and neutropenia include preexisting low white blood cell (WBC) count or absolute neutrophil count (ANC) and a history of drug-induced leukopenia or neutropenia
  • Perform a complete blood cell count frequently during the first few months of therapy
  • Consider discontinuation at the first sign of a clinically significant decline in WBC count in the absence of other causative factors
  • Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur
  • Discontinue therapy in patients with severe neutropenia (ANC less than 1000/mm3) and follow their WBC count until recovery
• Drug interaction overview
  • Strong CYP3A4 inducers
    • Not recommended
    • Strong CYP3A4 inducers decrease AUC and efficacy of Olanzapine-Samidorphan
  • Strong CYP1A2 inhibitors
    • Consider dosage reduction of olanzapine component
    • Strong CYP1A2 inhibitors increase olanzapine plasma concentrations and the risk of adverse reactions of Olanzapine-Samidorphan
  • CYP1A2 inducers
    • Consider dosage increase of olanzapine component
    • Strong CYP1A2 inducers decrease the effects of olanzapine and the efficacy of Olanzapine-Samidorphan
  • CNS acting drugs
    • Use with caution
    • Diazepam, alcohol, or other CNS-acting drugs may potentiate the orthostatic hypotension observed with olanzapine
  • Anticholinergic drugs
    • Use with caution
    • Olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility
  • Antihypertensive agents
    • Monitor BP and reduce the dosage of the antihypertensive drug by its prescribing information
    • Olanzapine-Samidorphan may enhance the effects of certain antihypertensive agents
  • Levodopa and dopamine agonists
    • Not recommended
    • Olanzapine-Samidorphan may antagonize the effects of levodopa and dopamine agonists

Pregnancy and Lactation

• No data are available on the use of samidorphan or Olanzapine-Samidorphan in pregnant females to determine drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Olanzapine
  • Neonates exposed to antipsychotic drugs, including olanzapine, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery
  • Overall published epidemiologic studies of pregnant females exposed to olanzapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Pregnancy exposure registry
  • Monitors pregnancy outcomes in women exposed to atypical antipsychotics during pregnancy
  • Encourage patients to register by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/
• Infertility
  • Based on the pharmacologic action of olanzapine (D2 antagonism), an increase in serum prolactin levels may occur, which may lead to a reversible reduction in fertility in females of reproductive potential
• Clinical considerations
  • Disease-associated maternal and/or embryo-fetal risk
  • There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including an increased risk of relapse, hospitalization, and suicide
  • Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth
  • Unknown if a direct result of the illness or other comorbid factors
• Fetal or 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, during the third trimester of pregnancy; symptoms vary 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
• Lactation
• Olanzapine
  • Present in human milk
  • There are reports of excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements) in infants exposed to olanzapine through breast milk
  • There is no information on the effects of olanzapine on milk production
• Samidorphan
  • There are no data on the presence of samidorphan or Olanzapine-Samidorphan in human milk, effects on breastfed infants, or effects on milk production
  • When administered to lactating rats, samidorphan and a metabolite were detected in the plasma of nursing pups, likely due to the presence of samidorphan in milk
  • Monitor infants exposed to Olanzapine-Samidorphan for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements)