Nrf2 activator Pregnancy: US label §8.1: there are no adequate data on the developmental risks associated with use in pregnant women. In animal studies, administration during pregnancy, or throughout pregnancy and lactation, produced evidence of developmental toxicity (embryofetal mortality and growth impairment, and mortality, growth impairment and neurobehavioural deficits in offspring) at plasma exposures similar to or less than exposures in humans. A pregnancy exposure registry monitors outcomes in women exposed during pregnancy. UK SPC §4.6 wording was not captured - clinician to check the SPC.

Omaveloxolone

Brand names: Skyclarys

Omaveloxolone is an oral agent used in the treatment of Friedreich's ataxia, a progressive inherited neurodegenerative disorder.

Adult dose

Dose: 150 mg (3 x 50 mg capsules) once daily

Route: Oral - on an empty stomach, at least 1 hour before or 2 hours after eating. Swallow capsules whole; do not crush or chew.

Frequency: Once daily

SOURCE CAVEAT: no UK SPC (eMC) record was captured in this bundle - the dose above is from the US prescribing information for SKYCLARYS (Biogen, label date 2026-04-06), indicated for Friedreich's ataxia. Verify against the current UK SPC. TESTING BEFORE AND DURING TREATMENT (US §2.1): obtain ALT, AST, bilirubin, B-type natriuretic peptide (BNP) and lipid parameters before initiating and during treatment; monitor ALT, AST and total bilirubin before initiation, every month for the first 3 months, and periodically thereafter; monitor cholesterol periodically. ADMINISTRATION: for patients unable to swallow whole capsules, the capsules may be opened and the entire contents of both halves sprinkled onto 2 tablespoons (30 mL) of applesauce, stirred until homogenous and swallowed immediately - do not store the mixture, do not mix with milk or orange juice, and it is not for enteral feeding tube administration. MISSED DOSE: take the next dose at its scheduled time the following day; do not take a double dose to make up for a missed dose. DOSE MODIFICATION FOR CYP3A4 INTERACTIONS (US §2.4): avoid concomitant use with strong CYP3A4 inhibitors - if unavoidable, reduce to 50 mg once daily with close monitoring, and discontinue the inhibitor if adverse reactions emerge; avoid concomitant use with moderate CYP3A4 inhibitors - if unavoidable, reduce to 100 mg once daily with close monitoring and reduce further to 50 mg once daily if adverse reactions emerge; avoid concomitant use with strong or moderate CYP3A4 inducers. HEPATIC IMPAIRMENT (US §2.5): mild (Child-Pugh A) 150 mg once daily; moderate (Child-Pugh B) 100 mg once daily with close monitoring, considering a reduction to 50 mg once daily if adverse reactions emerge; severe (Child-Pugh C) avoid use. PAEDIATRIC (US §8.4): safety and effectiveness have been established in paediatric patients aged 16 years and older (the same 150 mg once-daily dose was studied) but have NOT been established below 16 years of age - no separate per-kg paediatric dose is given in the source; verify any under-18 use against a children's formulary. ELDERLY (US §8.5): clinical studies did not include patients aged 65 and over and no data are available to determine whether they respond differently.

Dose independently re-sourced from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

None (US label §4)

Side effects

Elevated liver enzymes (AST/ALT) - incidence at least 20% and greater than placebo; ALT or AST above 5x and 3x the upper limit of normal occurred in 16% and 31% of treated patients respectively, with maximum increases within 12 weeks of starting
Headache - incidence at least 20% and greater than placebo
Nausea and abdominal pain - incidence at least 20% and greater than placebo
Fatigue and diarrhoea - incidence at least 20% and greater than placebo
Musculoskeletal pain - incidence at least 20% and greater than placebo; elevation of B-type natriuretic peptide (advise patients of the signs and symptoms of fluid overload) and lipid abnormalities are also labelled warnings

Interactions

Strong CYP3A4 inhibitors - omaveloxolone is a CYP3A4 substrate; concomitant use is expected to increase exposure clinically significantly. Avoid; if unavoidable reduce the dose to 50 mg once daily (US label §7.1, §2.4)
Moderate CYP3A4 inhibitors - avoid; if unavoidable reduce the dose to 100 mg once daily, and to 50 mg once daily if adverse reactions emerge (US label §7.1, §2.4)
Moderate or strong CYP3A4 inducers - expected to reduce omaveloxolone exposure clinically significantly and may reduce effectiveness; avoid concomitant use (US label §7.1)
CYP3A4 and CYP2C8 substrates - omaveloxolone is a weak inducer of CYP3A4 and CYP2C8 and can reduce the exposure and activity of these substrates (US label §7.2)

Clinical monograph

How it works

It activates the Nrf2 transcription factor, upregulating antioxidant and mitochondrial defence pathways to counter the oxidative stress and mitochondrial dysfunction characteristic of Friedreich's ataxia.

Prescribing in practice

Monitor liver function, as elevations in transaminases can occur, and check before and periodically during treatment as advised in the SPC.
Lipid parameters and B-type natriuretic peptide may change, so review these during treatment.
Several medicines interact via cytochrome P450 pathways, so review concomitant therapy against current prescribing references.

Monitoring

Monitor liver function tests, lipids and weight periodically during treatment.

Counselling the patient

Take consistently with respect to food as directed and do not take with a high-fat meal unless advised.
Attend for blood tests to check your liver during treatment.
Tell your clinician about all other medicines, as interactions are possible.

Evidence & guidelines

Omaveloxolone is approved for Friedreich's ataxia on the basis of a randomised trial showing improvement in neurological function as measured by a standard ataxia rating scale.

Reference: NICE; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Pathways