Omaveloxolone

SKYCLARYS

What it isNRF2 activator restoring antioxidant response; Friedreich ataxia.

Why this oneIt was the first treatment approved specifically for the disease.

What limits itMonitor liver enzymes and BNP; strong CYP3A4 inhibitors raise exposure, and BNP elevation may signal cardiac dysfunction.

FDA label

FDA dosing	Population	Start	Target	Max
Friedreich's ataxia	Adults and peds 16 years and older	150 mg (3 capsules) QD on empty stomach		150 mg QD

Renal Undefined

Hepatic Mild (Child-Pugh A): 150 mg QD; Moderate (B): 100 mg QD, reduce to 50 mg QD if adverse reactions; Severe (C): avoid use

If strong/moderate CYP3A4 inhibitor unavoidable: reduce to 50/100 mg QD respectively with close monitoring; avoid strong/moderate CYP3A4 inducers

Take on empty stomach: at least 1 h before or 2 h after eating
Swallow capsules whole (do not crush/chew), or open and sprinkle entire contents on 2 tbsp applesauce and take immediately; not with milk or orange juice; not for enteral feeding tubes
Missed dose: skip; do not double next dose
Obtain ALT/AST, bilirubin, BNP, and lipid panel before initiation and during treatment

Aminotransferase elevations (ALT/AST >3x ULN in 31%): monitor ALT/AST/bilirubin monthly x3 months then periodically; discontinue if >5x ULN, or >3x ULN with liver dysfunction
BNP elevation — may indicate cardiac failure (cardiomyopathy common in Friedreich's ataxia): check BNP at baseline; monitor for fluid overload (rapid weight gain, edema, palpitations, dyspnea)
Lipid abnormalities (increased LDL-C, decreased HDL-C): monitor lipids periodically
May reduce hormonal contraceptive efficacy — use non-hormonal/additional contraception during and 28 days after treatment

Pregnancy No adequate human data; developmental toxicity in animals at exposures at or below clinical; pregnancy exposure registry available

Lactation No human data; present in rat milk; weigh benefits vs risk

NO BOXED WARNINGS

Principal riskTransaminase rise; sensitive 3A4 substrate

Direct muscarinic antagonism0 / 4