SKYCLARYS: Uses, Dosage & Side Effects
An Nrf2 activator for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older
SKYCLARYS (omaveloxolone) is a prescription medication approved for the treatment of Friedreich's ataxia (FA) in adults and adolescents aged 16 years and older. Friedreich's ataxia is a rare, inherited neurodegenerative disorder caused by a deficiency in the protein frataxin, which leads to mitochondrial dysfunction and excessive oxidative stress. SKYCLARYS works by activating nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor that regulates the body's antioxidant defenses. In clinical trials, SKYCLARYS demonstrated statistically significant improvements in neurological function as measured by the modified Friedreich's Ataxia Rating Scale (mFARS) compared with placebo. SKYCLARYS is taken orally as 150 mg (three capsules) once daily on an empty stomach and represents the first approved treatment specifically designed to address the underlying oxidative stress pathology in Friedreich's ataxia.
Quick Facts: SKYCLARYS
Key Takeaways
- SKYCLARYS (omaveloxolone) is the first approved therapy specifically targeting the Nrf2 pathway in Friedreich's ataxia, a rare hereditary neurodegenerative disease affecting approximately 1 in 50,000 people.
- The recommended dose is 150 mg (three 50 mg capsules) taken once daily on an empty stomach, at least 1 hour before or 2 hours after eating. Capsules can be opened and sprinkled on applesauce for patients who cannot swallow them whole.
- SKYCLARYS has numerous important drug interactions due to CYP3A4 metabolism, including with antifungals, antibiotics, anticonvulsants, and hormonal contraceptives. Always inform your doctor of all medications you take.
- Regular monitoring of liver function, cholesterol, triglycerides, and BNP is required during treatment. Report any sudden weight gain, leg swelling, or shortness of breath to your doctor immediately.
- SKYCLARYS must not be used during pregnancy, and hormonal contraceptives are unreliable while taking this medication. Non-hormonal contraception (copper IUD or barrier methods) should be used during treatment and for 28 days after stopping.
What Is SKYCLARYS and What Is It Used For?
SKYCLARYS contains the active substance omaveloxolone, a small molecule that belongs to a novel pharmacological class known as Nrf2 activators. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a pivotal role in the cellular defense against oxidative stress. Under normal conditions, Nrf2 is activated in response to oxidative damage and translocates to the cell nucleus, where it binds to antioxidant response elements (AREs) in the DNA and promotes the transcription of hundreds of cytoprotective and antioxidant genes. These genes encode enzymes involved in glutathione synthesis, heme oxygenase activity, quinone reduction, and the elimination of reactive oxygen species (ROS), collectively forming the cell's primary shield against oxidative injury.
Friedreich's ataxia (FA) is a rare autosomal recessive neurodegenerative disorder that affects approximately 1 in 50,000 individuals worldwide. It is caused by an expansion of the GAA trinucleotide repeat in the frataxin (FXN) gene on chromosome 9, which leads to a marked deficiency of the mitochondrial protein frataxin. Frataxin is essential for iron-sulfur cluster assembly in the mitochondria, and its deficiency results in iron accumulation within mitochondria, impaired electron transport chain function, excessive production of reactive oxygen species, and ultimately cellular energy failure. The tissues most vulnerable to this process are the dorsal root ganglia, the dentate nucleus of the cerebellum, the corticospinal tracts, and the myocardium.
In patients with Friedreich's ataxia, the Nrf2 pathway is significantly impaired. The combination of frataxin deficiency and increased oxidative stress leads to a vicious cycle of mitochondrial dysfunction and neuronal damage. By activating Nrf2, omaveloxolone helps restore the cell's natural antioxidant defenses, reduces oxidative damage to neurons and cardiac cells, and slows the progressive neurodegeneration that characterizes the disease. This mechanism of action directly addresses one of the fundamental pathological processes underlying Friedreich's ataxia, rather than merely treating symptoms.
The clinical efficacy of SKYCLARYS was demonstrated in the pivotal MOXIe trial, a randomized, double-blind, placebo-controlled Phase II study that enrolled 103 patients with Friedreich's ataxia aged 16 to 40 years. In Part 2 of the MOXIe trial, patients were randomized to receive either omaveloxolone 150 mg or placebo once daily for 48 weeks. The primary endpoint was the change from baseline in the modified Friedreich's Ataxia Rating Scale (mFARS) score, a validated clinical instrument that assesses neurological function across four domains: bulbar function, upper limb coordination, lower limb coordination, and upright stability and gait. Patients treated with omaveloxolone showed a statistically significant improvement in mFARS score compared with placebo, with a least-squares mean difference of approximately 2.40 points (p = 0.014). This improvement is clinically meaningful in the context of Friedreich's ataxia, where the natural disease course involves a progressive increase in mFARS score of approximately 1 to 2 points per year.
SKYCLARYS was first approved by the U.S. Food and Drug Administration (FDA) in February 2023, marking a historic milestone as the first medication specifically approved for the treatment of Friedreich's ataxia in the United States. The European Medicines Agency (EMA) subsequently granted conditional marketing authorization for SKYCLARYS in the European Union in February 2024. These approvals have provided patients with Friedreich's ataxia and their families with the first disease-modifying treatment option after decades of reliance on supportive care alone.
Friedreich's ataxia typically presents in childhood or adolescence, usually between the ages of 5 and 15 years. Symptoms include progressive difficulty with walking and balance (gait ataxia), impaired coordination of the hands and arms, speech difficulties (dysarthria), scoliosis, and cardiomyopathy. While the disease is progressive, the rate of progression varies between individuals. SKYCLARYS offers the first targeted pharmacological intervention to help slow the neurological decline associated with this condition.
What Should You Know Before Taking SKYCLARYS?
Contraindications
The primary contraindication to SKYCLARYS use is hypersensitivity (allergy) to omaveloxolone or to any of the other ingredients in the capsule formulation. The excipients in SKYCLARYS include pregelatinized maize starch, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, and colloidal anhydrous silica. The capsule shell contains hypromellose, titanium dioxide (E171), brilliant blue FCF (E133), and yellow iron oxide (E172). If you have a known allergy to any of these substances, you must not use SKYCLARYS. Inform your doctor about all allergies before starting treatment.
Warnings and Precautions
SKYCLARYS can cause elevated liver enzymes (ALT, AST, bilirubin). Your doctor will perform liver function tests before starting treatment and at regular intervals during therapy. If your liver enzyme levels rise significantly, your doctor may need to reduce your dose or temporarily discontinue treatment. Report any symptoms of liver problems such as unusual tiredness, nausea, vomiting, abdominal pain, dark urine, or yellowing of the skin or eyes to your doctor immediately.
Before starting SKYCLARYS, your doctor will conduct several baseline assessments and discuss the following important considerations:
- Liver function: Elevated liver enzymes (transaminases) have been observed in clinical trials with omaveloxolone. Your doctor will measure your ALT, AST, and bilirubin levels before initiating therapy and will monitor them regularly throughout treatment. If significant elevations occur, dose reduction or temporary discontinuation may be necessary. Patients with pre-existing liver disease should be carefully evaluated before starting SKYCLARYS.
- Cholesterol and triglycerides: SKYCLARYS may cause changes in blood lipid levels, including increases in total cholesterol and triglycerides. Your doctor will check your lipid profile before starting treatment and at regular intervals. If significant elevations occur, appropriate management strategies will be discussed.
- B-type natriuretic peptide (BNP): Elevated BNP levels, which can indicate cardiac stress, have been observed in some patients taking SKYCLARYS. Given that cardiomyopathy is a common manifestation of Friedreich's ataxia, monitoring BNP is particularly important. Contact your doctor immediately if you experience sudden weight gain, swollen legs, ankles, or feet, or shortness of breath, as these may be signs of heart problems.
- Hypersensitivity reactions: Allergic reactions have been reported with SKYCLARYS. If you develop signs of a hypersensitivity reaction such as rash, itching, swelling, or difficulty breathing, seek medical attention promptly.
- Weight loss: Weight loss has been reported as a very common side effect of SKYCLARYS. Your doctor will monitor your weight during treatment. Report any significant or unexplained weight loss to your healthcare provider, as this may require nutritional assessment and intervention.
Children and Adolescents
SKYCLARYS is approved for use in adolescents aged 16 years and older. It has not been studied in children under 16 years of age, and its safety and efficacy have not been established in this younger age group. The dosing recommendations for adolescents aged 16 and older are the same as for adults. For children under 16 with Friedreich's ataxia, healthcare providers should discuss alternative management strategies and the potential for future clinical data to support use in younger patients.
Pregnancy, Contraception, and Breastfeeding
SKYCLARYS must not be used during pregnancy. If you become pregnant while taking SKYCLARYS, stop taking the medication and inform your doctor immediately. SKYCLARYS reduces the effectiveness of hormonal contraceptives (birth control pills, patches, rings, implants, and hormonal IUDs). Women of childbearing potential must use effective non-hormonal contraception, such as a copper intrauterine device (IUD) or barrier methods (condoms, diaphragm with spermicide), during treatment and for 28 days after stopping SKYCLARYS.
The effects of omaveloxolone on human pregnancy have not been adequately studied. Based on preclinical data and the mechanism of action, SKYCLARYS may cause harm to a developing fetus. Women of childbearing potential should have a pregnancy test before starting treatment and should use effective non-hormonal contraception throughout therapy and for at least 28 days after the last dose. The critical point is that SKYCLARYS induces enzymes that metabolize hormonal contraceptives, rendering them less effective or potentially ineffective. Therefore, reliance on hormonal birth control alone is not sufficient during SKYCLARYS treatment.
Breastfeeding is not recommended while taking SKYCLARYS. It is not known whether omaveloxolone is excreted in human breast milk, but a risk to the breastfed infant cannot be excluded. The decision to breastfeed during SKYCLARYS treatment should be made in consultation with your doctor, weighing the benefits of breastfeeding for the infant against the benefits of treatment for the mother.
Driving and Operating Machinery
SKYCLARYS may cause fatigue, which is a very common side effect. If you experience fatigue or tiredness while taking SKYCLARYS, you should avoid driving or operating machinery until you know how the medication affects you. It is important to note that Friedreich's ataxia itself impairs coordination and balance, which may independently affect the ability to drive or operate equipment safely. Discuss with your doctor whether driving is appropriate for your individual situation.
How Does SKYCLARYS Interact with Other Drugs?
Unlike monoclonal antibody therapies that have minimal drug interactions, SKYCLARYS (omaveloxolone) is a small molecule that is extensively metabolized by cytochrome P450 enzymes, particularly CYP3A4. This means that many commonly used medications can affect SKYCLARYS blood levels, and SKYCLARYS itself can alter the effectiveness of other drugs. Understanding these interactions is critical for safe and effective treatment.
The drug interactions with SKYCLARYS fall into three main categories: drugs that increase SKYCLARYS levels (increasing the risk of side effects), drugs that decrease SKYCLARYS levels (reducing its therapeutic effectiveness), and drugs whose effectiveness is reduced by SKYCLARYS. Your doctor will carefully review all your medications before starting SKYCLARYS and may need to adjust doses or substitute alternative therapies.
Drugs That Increase SKYCLARYS Levels
Strong and moderate CYP3A4 inhibitors can increase the blood concentration of omaveloxolone, potentially leading to an increased risk of side effects. When these medications are necessary, your doctor may reduce the SKYCLARYS dose to minimize the risk of adverse reactions.
| Drug | Drug Class | Clinical Significance |
|---|---|---|
| Itraconazole | Antifungal | Strong CYP3A4 inhibitor – dose reduction may be needed |
| Ketoconazole | Antifungal | Strong CYP3A4 inhibitor – dose reduction may be needed |
| Fluconazole | Antifungal | Moderate CYP3A4 inhibitor – monitor closely |
| Clarithromycin | Macrolide antibiotic | Strong CYP3A4 inhibitor – dose reduction may be needed |
| Ciprofloxacin | Fluoroquinolone antibiotic | Moderate CYP3A4 inhibitor – monitor closely |
| Ciclosporin | Immunosuppressant | CYP3A4 inhibitor – dose reduction may be needed |
| Fluvoxamine | SSRI antidepressant | CYP3A4 inhibitor – monitor closely |
Drugs That Decrease SKYCLARYS Effectiveness
Strong and moderate CYP3A4 inducers can decrease omaveloxolone blood levels, potentially reducing the therapeutic effectiveness of SKYCLARYS. Co-administration with strong CYP3A4 inducers should be avoided whenever possible.
| Drug / Substance | Category | Clinical Significance |
|---|---|---|
| Rifampicin | Antibiotic (anti-TB) | Strong CYP3A4 inducer – avoid co-administration |
| Carbamazepine | Anticonvulsant | Strong CYP3A4 inducer – avoid co-administration |
| Phenytoin | Anticonvulsant | Strong CYP3A4 inducer – avoid co-administration |
| Phenobarbital | Anticonvulsant / Barbiturate | Strong CYP3A4 inducer – avoid co-administration |
| Primidone | Anticonvulsant | CYP3A4 inducer – avoid co-administration |
| Efavirenz | Antiretroviral (HIV) | Moderate CYP3A4 inducer – monitor closely |
| St. John's wort | Herbal supplement | Strong CYP3A4 inducer – avoid co-administration |
Drugs Whose Effectiveness Is Reduced by SKYCLARYS
SKYCLARYS can induce certain metabolic enzymes and transporters, leading to decreased blood levels and reduced effectiveness of several important medications. Patients taking these medications may require dose adjustments or alternative therapies.
| Drug | Drug Class | Clinical Recommendation |
|---|---|---|
| Midazolam | Benzodiazepine | Monitor for reduced sedative effect |
| Repaglinide | Antidiabetic (meglitinide) | Monitor blood glucose; dose adjustment may be needed |
| Rosuvastatin | Statin (HMG-CoA inhibitor) | Monitor cholesterol; dose adjustment may be needed |
| Hormonal contraceptives | Contraception | Use non-hormonal methods (copper IUD, barrier methods) |
Avoid grapefruit and grapefruit juice while taking SKYCLARYS. Grapefruit is a known CYP3A4 inhibitor that can increase blood levels of omaveloxolone, potentially leading to an increased risk of side effects. This applies to all grapefruit products including whole fruit, juice, and extracts.
Given the complexity of SKYCLARYS drug interactions, it is essential to provide your doctor and pharmacist with a complete list of all medications you are taking, including prescription drugs, over-the-counter medications, vitamins, and herbal supplements. Any time a new medication is started or stopped during SKYCLARYS treatment, consult your healthcare provider to check for potential interactions. Do not start or stop any medication without first discussing it with your doctor.
What Is the Correct Dosage of SKYCLARYS?
SKYCLARYS should always be used exactly as your doctor has instructed. The medication is available as hard capsules, each containing 50 mg of omaveloxolone. The standard treatment regimen is straightforward, but careful attention to timing with food is essential for optimal drug absorption and efficacy.
Standard Adult and Adolescent Dose (16 years and older)
Dose: 150 mg (three 50 mg capsules) once daily
Timing: Take on an empty stomach, at least 1 hour before or 2 hours after eating
Administration: Swallow capsules whole with water. Take at the same time each day.
Food interaction: Food significantly affects the absorption of omaveloxolone. Taking SKYCLARYS with food can increase drug levels unpredictably, which is why fasting conditions are required.
For Patients Who Cannot Swallow Capsules
If you are unable to swallow capsules whole, SKYCLARYS capsules can be opened and the contents sprinkled on food. Follow these steps carefully:
- Prepare applesauce: Place approximately 2 tablespoons (about 30 mL) of soft applesauce into a small bowl or cup.
- Open capsules: Carefully open each of the three capsules and sprinkle the entire contents onto the applesauce.
- Mix gently: Stir the mixture briefly to distribute the capsule contents throughout the applesauce.
- Eat immediately: Consume the entire applesauce mixture immediately after preparation. Do not store the mixture for later use.
- Do not chew: Swallow the mixture without chewing the capsule granules.
Dose Adjustments
Your doctor may need to adjust your SKYCLARYS dose in certain clinical situations. If you are taking medications that inhibit CYP3A4 (such as certain antifungals or antibiotics), your doctor may reduce the SKYCLARYS dose to avoid excessive drug levels and increased side effects. Similarly, if your liver function tests show significant elevations, your doctor may temporarily reduce the dose or suspend treatment until liver enzymes return to acceptable levels. Do not adjust your dose on your own without consulting your healthcare provider.
Missed Dose and Vomiting
If you miss a dose of SKYCLARYS, do not take the missed dose. Simply take your next scheduled dose at the usual time. Do not take a double dose to make up for a forgotten one. If you vomit after taking your dose, regardless of how soon after administration, do not take a replacement dose. Wait and take your next dose at the regularly scheduled time the following day. Using a daily alarm or medication reminder app can help you remember to take SKYCLARYS consistently at the same time each day.
The requirement to take SKYCLARYS on an empty stomach is not merely a recommendation but a critical aspect of proper dosing. Food, particularly high-fat meals, can significantly alter the absorption of omaveloxolone, leading to unpredictable blood levels. Consistent fasting administration ensures that the drug reaches reliable therapeutic levels, maximizing efficacy while minimizing the risk of dose-related side effects. Plan your daily schedule to accommodate the 1-hour pre-meal or 2-hour post-meal window.
What Are the Side Effects of SKYCLARYS?
Like all medicines, SKYCLARYS can cause side effects, although not everyone who takes it will experience them. The side effects observed during clinical trials are categorized below by their frequency of occurrence. Understanding the potential side effects allows you and your healthcare provider to monitor for them proactively and manage them appropriately if they occur.
In the MOXIe clinical trial, the overall incidence of adverse events was higher in the omaveloxolone group compared with placebo, with gastrointestinal side effects and elevated liver enzymes being the most notable differences. Most adverse events were mild to moderate in severity, and serious adverse events were uncommon. The discontinuation rate due to adverse events was relatively low, suggesting that SKYCLARYS is generally tolerable for most patients.
Very Common
May affect more than 1 in 10 people
- Nausea
- Diarrhea
- Vomiting
- Abdominal (stomach) pain
- Weight loss
- Elevated liver enzymes (ALT, AST)
- Headache
- Fatigue (tiredness)
- Sore throat (oropharyngeal pain)
- Back pain
- Muscle spasms
- Influenza (flu)
- Decreased appetite
- Hypersensitivity reactions
Common
May affect up to 1 in 10 people
- Elevated B-type natriuretic peptide (BNP)
- Changes in cholesterol and triglyceride levels
- Urinary tract infection
- Menstrual pain (dysmenorrhea)
Gastrointestinal side effects, particularly nausea, diarrhea, and vomiting, are among the most frequently reported adverse events with SKYCLARYS. These symptoms tend to be most prominent during the initial weeks of treatment and often improve or resolve as the body adjusts to the medication. Taking SKYCLARYS on an empty stomach as directed may help minimize nausea. If gastrointestinal symptoms are severe or persistent, your doctor may consider temporary dose reduction or prescribe anti-nausea medication.
Elevated liver enzymes (transaminases) require particular attention. In clinical trials, increases in ALT and AST were observed in a significant proportion of patients taking omaveloxolone. In most cases, these elevations were asymptomatic and reversible with dose adjustment or temporary discontinuation. However, your doctor will perform regular liver function tests to monitor for this effect. If you develop symptoms suggestive of liver injury, such as unusual tiredness, loss of appetite, right upper abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes), contact your doctor immediately.
Weight loss is a notable side effect that warrants ongoing monitoring. In the context of Friedreich's ataxia, where maintaining adequate nutrition and body weight can be challenging due to swallowing difficulties and impaired mobility, unintended weight loss may be clinically significant. Your doctor will monitor your weight at regular visits, and nutritional counseling may be recommended if weight loss becomes a concern.
Elevated BNP levels were observed in some patients, which is relevant given the cardiac involvement in Friedreich's ataxia. While elevated BNP does not necessarily indicate worsening heart function, it requires careful interpretation in the context of the underlying cardiac disease. Your doctor will integrate BNP monitoring with other cardiac assessments to ensure comprehensive cardiovascular surveillance.
Contact your doctor immediately if you experience: sudden weight gain, swelling of the legs, ankles, or feet, shortness of breath (possible signs of heart problems), yellowing of the skin or eyes (possible liver damage), severe or persistent nausea, vomiting, or abdominal pain, signs of a severe allergic reaction (rash, swelling, difficulty breathing), or any other unusual or concerning symptoms. Do not wait for your next scheduled appointment if you are concerned about a potential serious side effect.
How Should You Store SKYCLARYS?
One of the practical advantages of SKYCLARYS as an oral medication is that it does not require special storage conditions such as refrigeration. This simplifies daily use and makes the medication convenient for travel.
Follow these storage guidelines to ensure the quality and safety of your medication:
- Temperature: No special temperature storage requirements. Store at normal room temperature.
- Keep in original packaging: Store SKYCLARYS capsules in the original blister packaging or bottle to protect them from moisture and light.
- Keep out of reach of children: Store SKYCLARYS in a safe location where children cannot access it. The capsules should not be mistaken for candy or sweets by young children.
- Check expiry date: Do not use SKYCLARYS after the expiration date printed on the carton and blister pack. The expiration date refers to the last day of that month. Discard any expired medication.
- Do not use damaged capsules: If capsules appear broken, discolored, or damaged, do not use them. Contact your pharmacist for replacement.
- Disposal: Do not dispose of unused or expired SKYCLARYS capsules in household waste or down the drain. Return unused medication to your pharmacist for proper disposal in accordance with local regulations.
When traveling with SKYCLARYS, keep the medication in your carry-on luggage rather than checked baggage to avoid exposure to extreme temperatures. Bring enough medication for the duration of your trip plus a few extra days in case of unexpected delays. Carry a copy of your prescription or a letter from your doctor confirming that you require the medication.
What Does SKYCLARYS Contain?
Understanding the composition of your medication is important, particularly if you have allergies or sensitivities to pharmaceutical ingredients. Below is a comprehensive breakdown of what SKYCLARYS capsules contain.
Active Ingredient
The active substance is omaveloxolone. Each hard capsule contains 50 mg of omaveloxolone. The standard daily dose of 150 mg requires taking three capsules.
Inactive Ingredients (Excipients)
| Ingredient | Role | Notes |
|---|---|---|
| Omaveloxolone | Active substance (Nrf2 activator) | 50 mg per capsule |
| Pregelatinized maize starch | Filler / binder | Provides capsule bulk and aids tablet formation |
| Microcrystalline cellulose | Filler / binder | Common pharmaceutical excipient |
| Croscarmellose sodium | Disintegrant | Helps capsule contents dissolve |
| Magnesium stearate | Lubricant | Facilitates manufacturing process |
| Colloidal anhydrous silica | Glidant | Improves powder flow during manufacturing |
Capsule Shell Composition
The capsule shell is made of hypromellose (a plant-derived polymer), colored with titanium dioxide (E171), brilliant blue FCF (E133), and yellow iron oxide (E172). The printing ink on the capsule contains shellac (E904) and titanium dioxide (E171). These colorants and printing materials are standard pharmaceutical-grade ingredients approved for use in medicinal products.
Appearance and Pack Sizes
SKYCLARYS capsules have a distinctive two-tone appearance: the bottom half is light green and marked with "RTA 408" in white ink, while the top half is blue and marked with "50" in white ink. This marking system helps identify the capsules and confirm the correct strength. SKYCLARYS is available in packs of 90 capsules (providing a 30-day supply at the standard dose of three capsules daily) or multi-packs of 3 × 90 capsules. Not all pack sizes may be marketed in every country.
Marketing Authorization Holder and Manufacturer
SKYCLARYS is marketed by Biogen Netherlands B.V. The drug was originally developed by Reata Pharmaceuticals (now part of Biogen) under the research designation RTA 408. In the United States, SKYCLARYS is marketed by Biogen Inc. The medication is available in the United States and the European Union, with additional regulatory submissions ongoing in other territories.
Frequently Asked Questions About SKYCLARYS
SKYCLARYS (omaveloxolone) is used for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older. Friedreich's ataxia is a rare inherited neurodegenerative disorder that causes progressive problems with movement, coordination, and balance. SKYCLARYS works by activating the Nrf2 pathway, which helps protect cells from oxidative stress damage that drives the disease. It is the first medication specifically approved to treat Friedreich's ataxia.
SKYCLARYS has a unique mechanism of action. It activates Nrf2, a key transcription factor that controls the body's antioxidant defenses. In Friedreich's ataxia, the genetic deficiency of frataxin leads to excessive oxidative stress and impaired Nrf2 activity, resulting in progressive damage to nerve cells and the heart. By restoring Nrf2 function, SKYCLARYS addresses one of the fundamental causes of cellular damage in the disease, rather than simply managing symptoms. This disease-modifying approach represents a new paradigm in treating Friedreich's ataxia.
SKYCLARYS must be taken on an empty stomach because food significantly affects the absorption of omaveloxolone. Taking the medication with food, especially high-fat meals, can increase drug levels unpredictably, which may lead to an increased risk of side effects. By taking SKYCLARYS in a fasting state (at least 1 hour before or 2 hours after eating), you ensure consistent and predictable absorption, which is essential for maintaining the correct therapeutic dose and minimizing side effects.
No, hormonal contraceptives (birth control pills, patches, rings, implants, and hormonal IUDs) may not be effective while taking SKYCLARYS. Omaveloxolone induces enzymes that break down hormonal contraceptives more rapidly, reducing their contraceptive effectiveness. If you need contraception while taking SKYCLARYS, you should use non-hormonal methods such as a copper intrauterine device (copper IUD) or barrier methods (condoms, diaphragm with spermicide). This precaution applies during treatment and for 28 days after your last dose of SKYCLARYS. Discuss the most appropriate contraceptive method with your doctor.
Your doctor will perform several blood tests before starting SKYCLARYS and at regular intervals during treatment. These include liver function tests (ALT, AST, and bilirubin) to monitor for liver enzyme elevations, lipid panels (cholesterol and triglycerides) as SKYCLARYS can affect blood fat levels, and B-type natriuretic peptide (BNP) measurements to monitor for potential cardiac effects. The frequency of monitoring will be determined by your doctor based on your individual response to treatment and any abnormalities detected. Regular monitoring allows early detection of potential problems so that dose adjustments can be made if necessary.
If you vomit after taking your dose of SKYCLARYS, do not take another dose to replace it, regardless of how soon after taking the capsules the vomiting occurred. Simply wait and take your next regular dose at the scheduled time the following day. Taking an additional dose after vomiting could result in unpredictable drug levels. If vomiting occurs frequently after taking SKYCLARYS, discuss this with your doctor, as they may recommend strategies to manage nausea or may need to reassess your treatment plan.
References
- European Medicines Agency (EMA). SKYCLARYS (omaveloxolone) – Summary of Product Characteristics. Conditional Marketing Authorization 2024. Available at: EMA SKYCLARYS EPAR.
- U.S. Food and Drug Administration (FDA). SKYCLARYS (omaveloxolone) – Prescribing Information. Biogen Inc. Approved February 2023.
- Lynch DR, Chin MP, Delatycki MB, et al. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann Neurol. 2021;89(2):212–225. doi:10.1002/ana.25934.
- Pandolfo M. Friedreich Ataxia: The Clinical Picture. J Neurol. 2009;256(Suppl 1):3–8. doi:10.1007/s00415-009-1002-3.
- Lynch DR, Farmer J, Hauser L, et al. Safety, Pharmacodynamics, and Potential Benefit of Omaveloxolone in Friedreich Ataxia. Ann Clin Transl Neurol. 2019;6(1):15–26. doi:10.1002/acn3.660.
- Friedreich's Ataxia Research Alliance (FARA). Understanding Friedreich's Ataxia. 2024. Available at: FARA.
- Campuzano V, Montermini L, Moltò MD, et al. Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion. Science. 1996;271(5254):1423–1427. doi:10.1126/science.271.5254.1423.
- Paupe V, Dassa EP, Goncalves S, et al. Impaired Nuclear Nrf2 Translocation Undermines the Oxidative Stress Response in Friedreich Ataxia. PLoS One. 2009;4(1):e4253. doi:10.1371/journal.pone.0004253.
- World Health Organization (WHO). Neurological Disorders: Public Health Challenges. 2023. Available at: WHO Brain Health.
- European Reference Network for Rare Neurological Diseases (ERN-RND). Friedreich Ataxia Clinical Guidelines. 2024.
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