olanzapine/samidorphan

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: Olanzapine: 93%.

Metabolism/Excretion: Olanzapine: Primarily metabolized in the liver via the CYP1A2 isoenzyme and UGT1A4 to inactive metabolites; primarily excreted in urine (57%; 7% as unchanged drug).

Half-Life: Olanzapine: 35–52 hr; samidorphan: 7–11 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4.5–7 hr (olanzapine); 1–2 hr (samidorphan)	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Using opioids or undergoing acute opioid withdrawal;
End-stage renal disease.

Use Cautiously in:

Cardiovascular or cerebrovascular disease;
Diabetes or risk factors for diabetes (may worsen glucose control);
History of seizures;
Patients at risk for aspiration or falls;
Low WBC or ANC or history of drug-induced neutropenia/leukopenia;
Presence/history of constipation, urinary retention, prostatic hypertrophy, or paralytic ileus;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children;
Geri: Appears on Beers list. risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for bipolar disorder or treatment-resistant depression.

Adv. Reactions/Side Effects ⬆ ⬇

CV: orthostatic hypotension, ↑blood pressure, syncope

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)

EENT: ↑salivation

Endo: hyperprolactinemia, galactorrhea, gynecomastia, hyperglycemia

GI: dry mouth, constipation, dyspepsia, dysphagia, ↑liver enzymes, nausea

GU: amenorrhea, ↓fertility (females), impotence

Hemat: AGRANULOCYTOSIS, leukopenia, neutropenia

Metab: dyslipidemia, ↑appetite, ↑weight

MS: bradykinesia, ↑creatine kinase, muscle spasms

Neuro: sedation, akathisia, dizziness, falls, fatigue, headache, NEUROLEPTIC MALIGNANT SYNDROME, restlessness, SEIZURES, speech impairment, tardive dyskinesia, tremor

Resp: aspiration

Misc: body temperature dysregulation

Interactions ⬆ ⬇

Drug-drug:

May precipitate opioid withdrawal in patients taking opioids; concurrent use contraindicated. Short-acting opioids should be discontinued for ≥7 days, and long-acting opioids should be discontinued for ≥14 days prior to initiating olanzapine/samidorphan therapy.
Antihypertensives and CNS depressants may ↑ risk of orthostatic hypotension.
↑anticholinergic effects with other anticholinergic drugs, including antihistamines, quinidine, disopyramide, and antidepressants; avoid concurrent use.
CYP3A inducers, including rifampin, may ↓ olanzapine and samidorphan levels and effectiveness; concomitant use not recommended.
Strong CYP1A2 inhibitors, including fluvoxamine, may ↑ olanzapine levels and risk of toxicity; consider ↓ olanzapine dosage.
CYP1A2 inducers, including, carbamazepine, may ↓ olanzapine levels and effectiveness; consider ↑ olanzapine dosage.
May antagonize the effects of levodopa or other dopamine agonists.

Route/Dosage ⬆ ⬇

Schizophrenia

PO (Adults ): Olanzapine 5 mg/samidorphan 10 mg or olanzapine 10 mg/samidorphan 10 mg once daily; may ↑ dose on weekly basis in 5-mg increments of olanzapine based on clinical response and tolerability (max = olanzapine 20 mg/samidorphan 10 mg once daily).
PO (Adults ≥65 yr or patients at risk for orthostatic hypotension): Olanzapine 5 mg/samidorphan 10 mg; may ↑ dose on weekly basis in 5-mg increments of olanzapine based on clinical response and tolerability (max = olanzapine 20 mg/samidorphan 10 mg once daily).

Bipolar I Disorder

PO (Adults ): Monotherapy: Olanzapine 10 mg/samidorphan 10 mg or olanzapine 15 mg/samidorphan 10 mg once daily; may ↑ dose no more frequently than every 24 hr in 5-mg increments of olanzapine based on clinical response and tolerability (max = olanzapine 20 mg/samidorphan 10 mg once daily). As adjunct to lithium or valproate: Olanzapine 10 mg/samidorphan 10 mg once daily; may ↑ dose on weekly basis in 5-mg increments of olanzapine based on clinical response and tolerability (max = olanzapine 20 mg/samidophan 10 mg once daily).
PO (Adults ≥65 yr or patients at risk for orthostatic hypotension): Monotherapy: Olanzapine 5 mg/samidorphan 10 mg once daily; may ↑ dose no more frequently than every 24 hr in 5-mg increments of olanzapine based on clinical response and tolerability (max = olanzapine 20 mg/samidophan 10 mg once daily). As adjunct to lithium or valproate: Olanzapine 5 mg/samidorphan 10 mg once daily; may ↑ dose on weekly basis in 5-mg increments of olanzapine based on clinical response and tolerability (max = olanzapine 20 mg/samidophan 10 mg once daily).

Availability ⬆ ⬇

Tablets: olanzapine 5 mg/samidorphan 10 mg; olanzapine 10 mg/samidorphan 10 mg; olanzapine 15 mg/samidorphan 10 mg; olanzapine 20 mg/samidorphan 10 mg

Assessment ⬆ ⬇

Assess mood, ideation, and behaviors frequently. Initiate suicide precautions if indicated. Monitor closely for changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
Monitor for development of neuroleptic malignant syndrome (fever, muscle rigidity, altered mental status, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness, loss of bladder control). Notify health care professional immediately if these symptoms occur.
Monitor for signs and symptoms of multiorgan hypersensitivity reactions—DRESS (rash, fever, lymphadenopathy). May be associated with other organ involvement (hepatitis, hepatic failure, blood dyscrasias, acute multiorgan failure). If cause cannot be determined, discontinue therapy immediately.
Monitor weight prior to starting Lybalvi and frequently thereafter.
Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue). Notify health care professional immediately if these symptoms occur, as these side effects may be irreversible.
Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.
Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).

Lab Test Considerations:

Monitor blood glucose and cholesterol levels prior to starting and periodically during therapy.
- Monitor CBC frequently during initial mos of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue Lybalvi in patients with severe neutropenia (absolute neutrophil count <1000/mm³) and follow their WBC until recovery.
- May cause false positive results with urinary immunoassay methods used for detecting opioids. Use an alternative analytical technique (e.g., chromatographic methods) to confirm positive opioid urine drug screen results.

Implementation ⬆ ⬇

Lybalvi is contraindicated in patients using opioids or undergoing acute opioid withdrawal. Samidorphan, part of Lybalvi, can precipitate opioid withdrawal in patients dependent on opioids, leading to opioid withdrawal syndrome, sometimes requiring hospitalization. In patients who use opioids, delay start of therapy for a minimum of 7 days after last use of short-acting opioids and 14 days after last use of long-acting opioids.
PO: Administer orally once daily with or without food as a single tablet. DNC: Do not divide tablets or combine strengths.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed.
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; may lead to life-threatening or fatal opioid intoxication (respiratory arrest, circulatory collapse).
Advise patient to change positions slowly to minimize orthostatic hypotension. Protect from falls.
May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide, new or worse depression, new or worse anxiety, feeling very agitated or restless, panic attacks, trouble sleeping, new or worse irritability, acting aggressive, being angry or violent, acting on dangerous impulses, an extreme increase in activity and talking, or other unusual changes in behavior or mood occur.
Advise patient to use sunscreen and protective clothing when exposed to the sun to prevent photosensitivity reactions. Extremes in temperature should also be avoided; this drug impairs body temperature regulation.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Caution patient to avoid concurrent use of alcohol and other CNS depressants, especially opioids.
Advise patient to notify health care professional of medication regimen before treatment or surgery.
Instruct patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, rash, tremors, or symptoms of hyperglycemia occur.
Rep: Advise female patients to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. Encourage women who become pregnant while taking Lybalvi to enroll in the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/. Advise patients that Lybalvi used during the 3rd trimester may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder). Monitor infants exposed to Lybalvi through breast milk for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements). Some neonates recovered within hrs or days without specific treatment; others required prolonged hospitalization. May impair fertility in females; usually reversible.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇