Omaveloxolone
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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Overview
Omaveloxolone is a Nuclear factor -like 2 (Nrf2) pathway activator that is FDA approved for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older.. Common adverse reactions include transamnitis, headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
omaveloxolone (SKYCLARYS) is used for the treatment of friedreich ataxia for adults and adolescents of age above 16 years.
The recommended dosage is 150mg (3 tablets of 50mg) taken orally once daily.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Omaveloxolone FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Contraindications
none
Warnings
Elevation of AST/ALT- In the clinical study it showed incidence of elevations of ALT or AST above 5 times and 3 times the upper limit of normal (ULN) was 16% and 31%, respectively, in patients treated with SKYCLARYS. Monitor ALT, AST, and total bilirubin prior to initiation of SKYCLARYS, every month for the first 3 months of treatment, and periodically thereafter. Discontinue SKYCLARYS and repeat liver function tests as soon as possible, if there is transaminases increase to levels greater than 5 times the ULN, or greater than 3 times the ULN with evidence of liver dysfunction (e.g., elevated bilirubin).
Elevation of B-Type Natriuretic Peptide- Treatment with SKYCLARYS can cause elevation in BNP. Cardiomyopathy and cardiac failure are common in patients with Friedreich's ataxia. Patient should be monitored for signs and symptoms of fluid overload like sudden weight gain (3 pounds or more of weight gain in one day, or 5 pounds or more of weight gain in a week), peripheral edema, palpitations, and shortness of breath.
Abnormalities in the lipid profile - In a study 29% of patients treated with SKYLARCY had elevated cholesterol above the UNL, A total of 16% of patients treated with SKYCLARYS had an increase in low-density lipoprotein cholesterol and 6% of patients treated with SKYCLARYS had decreases in high-density lipoprotein cholesterol (HDL-C) from baseline compared to 4% of patients who received placebo.
Adverse Reactions
Clinical Trials Experience
In the clinical trials where SKYCLARYS 150 mg was taken once daily by 165 patients with Friedreich's ataxia, including 137 patients being exposed for at least 48 weeks, and 125 patients being exposed for at least 96 weeks. It showed SKYCLARYS had common adverse effects of transamnitis, headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain. Furthermore, less adverse effects include back pain and spasm, rash and decreased appetite.
Postmarketing Experience
There is limited information regarding Omaveloxolone Postmarketing Experience in the drug label.
Drug Interactions
CYP3A4 Inhibitors: as Omaveloxolone is a CYP3A4 substrate, Concomitant use of SKYCLARYS with moderate or strong CYP3A4 inhibitors is expected to result in clinically significant increased exposure of omaveloxolone increasing the risk of adverse effects.
CYP3A4 Inducers: Similarly concomitant usage SKYCLARYS with CYP3A4 Inducers will lead to decrease efficacy of the drug.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): C
There was no evidence indicating development risk on using SKYCLARYS during pregnancy, however animal studies showed evidence of developmental toxicity (embryofetal mortality and growth impairment, and mortality, growth impairment, and neurobehavioral deficits in offspring.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Omaveloxolone in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Omaveloxolone during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Omaveloxolone in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Omaveloxolone in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Omaveloxolone in geriatric settings.
Gender
There is no FDA guidance on the use of Omaveloxolone with respect to specific gender populations.
Race
There is no FDA guidance on the use of Omaveloxolone with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Omaveloxolone in patients with renal impairment.
Hepatic Impairment
Omaveloxolone plasma exposure is increased in patients with moderate or severe hepatic impairment (Child-Pugh Class B and C) thus Avoid the treatment with SKYCLARYS in patients with severe hepatic impairment, including those who develop severe hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Omaveloxolone in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Omaveloxolone in patients who are immunocompromised.
Administration and Monitoring
Administration
SKYCLARYS 150 mg (3 capsules of 50mg) is administered orally once daily.
SKYCLARYS is taken on an empty stomach at least one hour before eating. Swallow SKYCLARYS capsules whole without being crushed or chewed. For patients who are unable to swallow whole capsules, SKYCLARYS capsules may be opened and the entire contents of both halves of the capsule sprinkled onto 2 tablespoons (30 mL) of applesauce and the whole mixture is swallowed. do not provide this mixture via enteral feed.
If a dose is missed, the next dose is taken as scheduled and it is never doubled for the next day.
Monitoring
Obtain ALT, AST, bilirubin, BNP, and lipid parameters prior to initiating SKYCLARYS and during treatment
IV Compatibility
There is limited information regarding the compatibility of Omaveloxolone and IV administrations.
Overdosage
There is limited information regarding Omaveloxolone overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Omaveloxolone Pharmacology in the drug label.
Mechanism of Action
although Omaveloxolone's precise mechanism remains unknown, Omaveloxolone have been shown to activate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in vitro and in vivo in animals and humans. The Nrf2 pathway is involved in the cellular response to oxidative stress.
Structure
There is limited information regarding Omaveloxolone Structure in the drug label.
Pharmacodynamics
There is limited information regarding Omaveloxolone Pharmacodynamics in the drug label.
Pharmacokinetics
Absorption The median (range) time to achieve peak plasma concentration (Tmax) was 7 to 14 (1 to 24) hours. Effect of Food
Omaveloxolone Cmax and AUC increased by approximately 350% and 15%, respectively, with a high-fat meal (800-1000 calories, approximately 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively) compared to fasting conditions.
Distribution The mean apparent volume of distribution of omaveloxolone is 105 L/kg for a 70 kg person with a protein binding of omaveloxolone is 97%.
Elimination The mean (range) terminal half-life of omaveloxolone is 57 hours (32 to 90 hours). Omaveloxolone is primarily metabolized by CYP3A with minor metabolism by CYP2C8 and CYP2J2.
Excretion approximately 92% of the dose was recovered in feces (approximately 91% within 96 hours after administration) and 0.1% in urine, following administration of a single oral dose of radiolabeled omaveloxolone 150 mg to healthy subjects,.
Nonclinical Toxicology
There is limited information regarding Omaveloxolone Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Omaveloxolone Clinical Studies in the drug label.
How Supplied
SKYCLARYS (omaveloxolone) capsules, 50 mg, are supplied as opaque, hard capsules having a light green body and blue cap imprinted with “RTA 408” in white ink on the body and “50” in white ink on the cap.
Storage
Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 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 Omaveloxolone Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Omaveloxolone interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Omaveloxolone Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Omaveloxolone 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.