olanzapine/samidorphan

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.

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

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).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Olanzapine: Antagonizes dopamine and serotonin type 2 in the CNS. Samidorphan: Acts as antagonist of the mu-opioid receptors to counterbalance the metabolic adverse effects of olanzapine.

Therapeutic effects:

Decreased symptoms of schizophrenia (with less weight gain compared to olanzapine).
Decreased symptoms of mania and/or depression association with bipolar I disorder.

Classifications ⬆ ⬇

Therapeutic Classification: antipsychotics, mood stabilizers

Pharmacologic Classification: thienobenzodiazepines, opioid antagonists

Pharmacokinetics ⬆ ⬇

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

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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Indications ⬇

Contraind./Precautions ⬆ ⬇