zuranolone

Absorption: Extent of absorption following oral administration unknown. Absorption increased with fat-containing foods.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Extensively metabolized in the liver via the CYP3A4 isoenzyme to inactive metabolites. 45% excreted in urine and 41% excreted in feces primarily as metabolites.

Half-Life: 19.7–24.6 hr.

Time/Action Profile ⬆ ⬇

(reduction in depressive symptoms)

ROUTE	ONSET	PEAK	DURATION
PO	3 days	unknown	at least 45 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy.

Use Cautiously in:

Moderate or severe renal impairment;
Severe hepatic impairment;
Rep: Women of reproductive potential;
Lactation: Enters breast milk; use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash

EENT: nasopharyngitis, sinus congestion

GI: abdominal pain, diarrhea, dry mouth

GU: urinary tract infection

MS: muscle twitching, myalgia

Neuro: dizziness, sedation, anxiety, confusion, fatigue, gait disturbances, memory impairment, SUICIDAL THOUGHTS/BEHAVIORS, tremor

Misc: physical dependence

Interactions ⬆ ⬇

Drug-drug:

Use with benzodiazepines or other CNS depressants, including opioids, non-benzodiazepine sedative/hypnotics, anxiolytics, muscle relaxants, and alcohol may cause profound sedation, loss of consciousness, and/or respiratory depression; avoid concurrent use, if possible; if concurrent use unavoidable, ↓ zuranolone dose.
Strong CYP3A4 inhibitors, including itraconazole, may ↑ levels and risk of toxicity; ↓ zuranolone dose.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 50 mg once daily in the evening for 14 days. If patients experience CNS adverse effects within the 14-day period, consider ↓ dose to 40 mg once daily in the evening within the 14-day period. Concurrent use of strong CYP3A4 inhibitors: 30 mg once daily in the evening for 14 days.

Renal Impairment

PO (Adults ): eGFR <60 mL/min/1.73 m²: 30 mg once daily in the evening for 14 days.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment: 30 mg once daily in the evening for 14 days.

Availability ⬆ ⬇

Capsules: 20 mg; 25 mg; 30 mg

Assessment ⬆ ⬇

Monitor mood changes. Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia.
Assess for suicidal tendencies, especially in patients ≤24 yr.

Implementation ⬆ ⬇

Administer once daily in the evening for 14 days with fat-containing food (400 to 1,000 calories, 25% to 50% fat).

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. If an evening dose is missed, take next dose at the regular time the following evening. Do not take extra capsules on the same day to make up for the missed dose. Continue taking zuranolone once daily until remainder of 14-day treatment course is completed. Advise patient to read Medication Guide before starting zuranolone.
Inform patients that zuranolone causes driving impairment due to CNS depressant effects. Caution patient to avoid driving and other activities requiring alertness until at least 12 hr after zuranolone administration for the duration of the 14-day treatment course. Inform patients that they may not be able to assess their own driving competence or the degree of driving impairment caused by zuranolone.
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. Advise patient to avoid taking other CNS depressants, including alcohol, benzodiazepines, opioids, and tricyclic antidepressants; may cause falls, somnolence, cognitive impairment, and the risk of respiratory depression.
Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide, new or worsening depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worsening irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior occur.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment with zuranolone and for one wk after the final dose. Advise a pregnant woman of the potential risk to an infant exposed to zuranolone in utero. Advise females with reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including zuranolone, during pregnancy. Health care professionals are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇