Skyclarys (omaveloxolone)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Omaveloxolone is a potent activator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is involved in the cellular response to oxidative stress.
Omaveloxolone is a semi-synthetic triterpenoid drug that increases antioxidant activity. The exact mechanism by which omaveloxolone exerts its therapeutic effect in patients with Friedreich's ataxia is unknown. Omaveloxolone has 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. In individuals with Friedreich's ataxia, the Nrf2 pathway is suppressed, which is associated with oxidative stress, mitochondrial dysfunction, and cell damage. Omaveloxolone may exert its effects by activating the Nrf2 pathway and blocking the degradation of Nrf2.
The median time to peak omaveloxolone plasma concentrations was 7-14 hours (range: 1-24 hours). In healthy fasted subjects, the omaveloxolone peak plasma concentrations increased in a less than dose-proportional manner over a dosage range of 50 mg (0.33 times the recommended dosage) to 150 mg. However, the total plasma drug exposure (AUC) increased in a dose-dependent and dose-proportional manner over the dosage range of 50-150 mg.
Omaveloxolone peak plasma concentrations and AUC were similar when capsule contents were sprinkled on applesauce or when administered as intact capsules. When sprinkled on applesauce, the median time to peak omaveloxolone plasma concentrations was shortened from approximately 10 to 6 hours. When administered with a high-fat meal (800-1000 calories, approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively), omaveloxolone peak plasma concentrations and AUC increased by approximately 350 and 15%, respectively, compared with fasted conditions.
Omaveloxolone is 97% protein bound. Omaveloxolone is primarily metabolized by cytochrome P-450 (CYP) isoenzyme 3A, with minor metabolism by CYP2C8 and CYP2J2. The mean terminal half-life is 57 hours (range: 32-90 hours).
Following oral administration of a single dose of radiolabeled omaveloxolone 150 mg in healthy subjects, approximately 92% of the dose was recovered in feces (approximately 91% within 96 hours of administration), and 0.1% was recovered in urine. There are no clinically important differences in omaveloxolone pharmacokinetics based on age (16-71 years of age), sex, race, or body weight (41-128 kg).
USES: Omaveloxolone is used to treat a certain disorder that affects nerves and muscles (Friedreich's ataxia). This disorder causes damage to your nerves, which results in loss of coordination and unsteady movements. Omaveloxolone may help to lessen symptoms of Friedreich's ataxia.
Generic name: omaveloxolone
Pronunciation: (OH-ma-vel-OX-oh-lone)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Skyclarys
Indications
The following indications are listed for Skyclarys:
- Friedreich's Ataxia
Dosing
If coadministration of omaveloxolone with a strong cytochrome P-450 (CYP) 3A4 inhibitor cannot be avoided, reduce omaveloxolone dosage to 50 mg once daily with close monitoring of adverse reactions. If adverse reactions emerge, discontinue coadministration with strong CYP3A4 inhibitors.
If coadministration of omaveloxolone with a moderate CYP3A4 inhibitor cannot be avoided, reduce omaveloxolone dosage to 100 mg once daily with close monitoring of adverse reactions. If adverse reactions emerge, further reduce omaveloxolone dosage to 50 mg once daily.
Omaveloxolone is administered orally.
Administer omaveloxolone capsules on an empty stomach at least 1 hour before or 2 hours after eating. Swallow the capsules whole; do not crush or chew.
For patients who are unable to swallow whole capsules, open the capsule(s) and sprinkle the entire contents of both halves of the capsule onto 2 tablespoons (30 mL) of applesauce. Stir the mixture until homogenous, and swallow the entire drug/applesauce mixture immediately. Do not store the mixture for future use. Do not mix contents of the capsule(s) with milk or orange juice. Do not administer via an enteral feeding tube.
If a dose of omaveloxolone is missed, take the next dose at its scheduled time the following day. Do not take a double dose to make up for a missed dose.
Store omaveloxolone capsules at 20-25oC (excursions permitted between 15-30oC).
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Drug interactions
Omaveloxolone is substrate of cytochrome P-450 (CYP) isoenzyme 3A4, and a weak inducer of CYP3A4 and CYPC8.
In vitro data indicate that omaveloxolone is not an inhibitor of CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP2D6, and not an inducer of CYP1A2 and CYP2B6.
In vitro data indicate that omaveloxolone inhibits the renal transporter, organic anion transporter (OAT)1. Omaveloxolone is not an inhibitor of breast cancer resistance protein (BCRP), bile salt export pump, OAT3, organic anion transport polypeptide (OATP)1B1, OATP1B3, organic cation transport 2, multidrug and toxin extrusion (MATE)1, and MATE2K.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse reactions with omaveloxolone (incidence >=20% and greater than placebo) are elevated liver enzymes (AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
The safety and effectiveness of omaveloxolone for the treatment of Friedreich's ataxia have been established in pediatric patients >=16 years of age, based on adequate evidence from the principal efficacy study. The safety and effectiveness of omaveloxolone have not been established in pediatric patients <16 years of age.
There are no adequate data on the developmental risks associated with the use of omaveloxolone in pregnant women. In animal studies, oral administration of omaveloxolone during pregnancy or throughout pregnancy and lactation resulted in developmental toxicity (embryofetal mortality and growth impairment, and mortality, growth impairment, and neurobehavioral deficits in offspring) at plasma exposures similar to or less than exposures in humans.
An exposure registry exists that monitors outcomes in women exposed to omaveloxolone during pregnancy. Patients or their healthcare providers can enroll in the registry by calling 1-866-609-1785 or emailing SkyclarysPregnancySurveillance@ppd.com.
No data are available on the presence of omaveloxolone or its metabolites in human milk. The effects of the drug on milk production or on breast-fed infants are unknown. Omaveloxolone was excreted in the milk of lactating rats following oral administration.
Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for omaveloxolone and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Clinical studies of omaveloxolone in Friedreich's ataxia did not include patients >=65 years of age. No data are available to determine whether geriatric patients respond differently than younger adults.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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