Zuranolone
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alen Antony Pathil, M.D.[2]
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Black Box Warning
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Impaired ability to engage in potential hazardous activity
See full prescribing information for complete Boxed Warning.
Patients are advised to avoid potential hazardous activity like driving for 12 hours after taking zuranolone during the 14 day treatment regimen.
Zuranolone causes driving impairment as it results in CNS depressing effects. Patients are also advised that they may not be able to assess their own driving competence, or the degree of driving impairment caused by ZURZUVAE. |
Overview
Zuranolone is a gamma-aminobutyric acid (GABA) A receptor positive modulator that is FDA approved for the treatment of postpartum depression (PPD) in adults. There is a Black Box Warning for this drug as shown here. Common adverse reactions include somnolence, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
ZURZUVAE is indicated for the treatment of postpartum depression (PPD) in adults.
The recommended dose of Zurzuvae is 50mg taken orally once daily for 14 days. It is ideally advised to be taken with fat containing food (e.g., 400 to 1,000 calories, 25% to 50% fat).
Zurzuvae is taken alone or as an adjunct to other antidepressant. The effectiveness and safety of this drug has not been studied beyond 14 days.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Zuranolone FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Contraindications
none
Warnings
|
Impaired ability to engage in potential hazardous activity
See full prescribing information for complete Boxed Warning.
Patients are advised to avoid potential hazardous activity like driving for 12 hours after taking zuranolone during the 14 day treatment regimen.
Zuranolone causes driving impairment as it results in CNS depressing effects. Patients are also advised that they may not be able to assess their own driving competence, or the degree of driving impairment caused by ZURZUVAE. |
1. Impaired Ability to Drive or Engage in Other Potentially Hazardous Activities Due to the central nervous system depressing effects, ZURZUVAE may impair the ability to drive or perform potentially hazardous activity. Thus, patients are who on ZUZUVAE are advised to refrain from driving for 12hrs after administering the drug during 14 day treatment course. They are also informed that they are not capable to assess their own ability to drive.
2. Central Nervous System Depressant Effects the effects are somnolence and confusion, thus putting the patients at a higher risk of fall. Other CNS depressants such as alcohol, benzodiazepines, opioids, tricyclic antidepressants, or drugs that increase zuranolone concentration, may increase impairment of psychomotor performance or CNS depressant effects such as somnolence, cognitive impairment, and the risk of respiratory depression in ZURZUVAE-treated patients. Therefore patients are advised to reduce the dosage of ZURZUVAE if they experience somnolence or confusion, or if they are taking it along other unavoidable CNS depressant drugs.
3. Suicidal Thoughts and Behavior consider discontinuing the drug if the patients experiences worsening of the depression or develops suicidal thoughts or behavior.
4. Embryo-fetal Toxicity as animal studies indicated that ZURZUVAE causes fetal harm like fetal malformations, embryofetal and offspring mortality, growth deficits, it is best avoided during pregnancy. Studies also showed that it caused neuronal death when rats were exposed to zuranolone during a period of brain development. Women are advised to be on contraceptives during the treatment course and also for 1 week following the last dose of ZURZUVAE.
Adverse Reactions
Clinical Trials Experience
In the placebo-controlled clinical studies in 347 women with PPD treated with 50 mg of ZURZUVAE (Study 1) once daily for 14 days, showed the most common adverse effects to be : somnolence (36%), dizziness(16%), diarrhea (6%), fatigue(5%), UTI(5%) and others being memory impairment, tremors, hypoesthesia, muscle twitching, myalgia, anxiety and rash.
While in another placebo-controlled clinical studies in 347 women with PPD treated with another zuranolone capsule formulation approximately equivalent to 40 mg of ZURZUVAE (Study 2) once daily for 14 days showed common adverse effects of : somnolence (19%), nasopharyngitis (9%), dizziness(8%) while other less common being fatigue , diarrhea, dry mouth, sinus congestion and tooth ache.
Postmarketing Experience
There is limited information regarding Zuranolone Postmarketing Experience in the drug label.
Drug Interactions
1. CNS depressant drug and alcohol. Concomitant administration of the above mentioned drugs with ZURZUVAE may increase impairment of psychomotor performance or CNS depressant effects. If the CNS depressant drug is unavoidable, suggest dosage reduction of ZURZUVAE.
2.Strong CYP3A4 Inhibitors Concomitant usage of ZURZUVAE with a strong CYP3A4 Inhibitors may result in prolonged exposure of ZURZUVAE increasing the risk of the adverse effects.
3.CYP3A4 Inducers concomitant usage of ZURZUVAE can cause decreased efficacy of ZURZUVAE.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): X oral administration of zuranolone to pregnant rats during organogenesis resulted in developmental toxicity, including embryofetal death and fetal malformations, with a no adverse effect level (NOAEL) associated with maternal plasma exposures 7 times greater than in humans at the maximum recommended human dose (MRHD) of 50 mg.
Neuronal death was observed in rats exposed to zuranolone during a period of brain development that begins during the third trimester of pregnancy in humans and continues up to a few years after birth.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Zuranolone in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Zuranolone during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Zuranolone in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Zuranolone in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Zuranolone in geriatric settings.
Gender
There is no FDA guidance on the use of Zuranolone with respect to specific gender populations.
Race
There is no FDA guidance on the use of Zuranolone with respect to specific racial populations.
Renal Impairment
The exposure to zuranolone was increased in patients with moderate (eGFR 30 to 59 mL/min/1.73 m2) and severe (eGFR 15 to 29 mL/min/1.73 m2) renal impairment . Therefore the dose of zuranolone is reduced in patients with moderate or severe renal impairment.
Hepatic Impairment
Exposure to zuranolone was increased in patients with severe hepatic impairment (Child-Pugh C). The recommended ZURZUVAE dosage in patients with severe hepatic impairment is therefore reduced.
However, no change in dosage is required for mild or moderate hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Zuranolone in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Zuranolone in patients who are immunocompromised.
Administration and Monitoring
Administration
The recommended dosage is 50 mg, administered orally once daily for 14 days. If a dose is missed, the missed dose is taken on the next day as the regular schedule, never double the dosage.
If the patient experiences CNS depressing effects like somnolence or confusion, reduce the dosage to 40mg. If the patient has severe hepatic impairment(child-Pugh C), the recommended dosage is 30 mg orally once daily in the evening for 14 days. If the patient has moderate or Severe Renal Impairment, the recommended dosage is 30 mg orally once daily in the evening for 14 days.
Monitoring
There is limited information regarding Zuranolone Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Zuranolone and IV administrations.
Overdosage
Overdosage with ZURZUVAE may result in excessive CNS depressant effects such as somnolence and disturbance in consciousness. There is no specific antidote for ZURZUVAE overdosage.
Pharmacology
There is limited information regarding Zuranolone Pharmacology in the drug label.
Mechanism of Action
The mechanism of action of zuranolone in the treatment of PPD is not fully understood, but is to be related to its positive allosteric modulation of GABAA receptors.
Structure
There is limited information regarding Zuranolone Structure in the drug label.
Pharmacodynamics
There is limited information regarding Zuranolone Pharmacodynamics in the drug label.
Pharmacokinetics
Zuranolone attains peak concentrations at 5 to 6 hours (Tmax) following oral administration.
The volume of distribution of zuranolone following oral administration is greater than 500 L with a plasma protein binding greater than 99.5%.
The terminal half-life of zuranolone is approximately 19.7 to 24.6 hours in an adult population with the mean apparent clearance (CL/F) of zuranolone is 33 L/h.
Zuranolone undergoes extensive metabolism, with CYP3A4 identified as a primary enzyme involved.
45% of the dose was excreted in urine as metabolites with negligible unchanged zuranolone and 41% in feces as metabolites with less than 2% as unchanged zuranolone.
Nonclinical Toxicology
There is limited information regarding Zuranolone Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Zuranolone Clinical Studies in the drug label.
How Supplied
ZURZUVAE (zuranolone) is supplied as 20 mg, 25 mg, and 30 mg capsules.
20mg capsule- light-orange cap, ivory to light-yellow body - available in a bottle on 14 capsules
25mg capsule- light-orange cap, light-orange body - available in a bottle on 14 capsules or blister pack of 28
30mg capsule- orange cap, light-orange body- available in a bottle on 14 capsules
Storage
Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F)
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Zuranolone Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Zuranolone interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
ZURZUVAE
Look-Alike Drug Names
There is limited information regarding Zuranolone Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.