WARNINGS AND PRECAUTIONS
Elevation of Aminotransferases: Treatment with SKYCLARYS can cause an elevation in
hepatic transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). The 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. There were no cases of concomitant elevation of
transaminases and total bilirubin observed. Maximum increases in ALT and AST occurred within 12 weeks
after starting SKYCLARYS. Increases in serum aminotransferases were generally asymptomatic and reversible
following discontinuation of SKYCLARYS. Patients with clinically significant liver disease were excluded
from the pivotal study.
Monitor ALT, AST, and total bilirubin prior to initiation of SKYCLARYS, every month for the first 3
months of treatment, and periodically thereafter. If 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),
immediately discontinue SKYCLARYS and repeat liver function tests as soon as possible. If transaminase
levels stabilize or resolve, SKYCLARYS may be reinitiated with an appropriate increased frequency of
monitoring of liver function.
Elevation of B-Type Natriuretic Peptide: Treatment with SKYCLARYS can cause an increase
in B-type natriuretic peptide (BNP), a marker of cardiac function. A total of 14% of patients treated with
SKYCLARYS had an increase from baseline in BNP value above the ULN (100 pg/mL), compared to 4% of patients
who received placebo. The incidence of elevation of BNP above 200 pg/mL was 4% in patients treated with
SKYCLARYS. Cardiomyopathy and cardiac failure are common in patients with Friedreich ataxia. Patients
were excluded from the pivotal study if they had BNP levels > 200 pg/mL prior to study entry, or a history
of clinically significant left-sided heart disease and/or clinically significant cardiac disease, with the
exception of mild to moderate cardiomyopathy associated with Friedreich ataxia. Whether the elevations
in BNP are related to SKYCLARYS or cardiac disease associated with Friedreich ataxia is unclear.
Elevations in BNP may indicate cardiac failure and should prompt an evaluation of cardiac function. Check
BNP prior to initiation of SKYCLARYS. Monitor patients for the signs and symptoms of fluid overload, such
as 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. If signs and symptoms of fluid overload
develop, worsen, or require hospitalization, evaluate BNP and cardiac function, and manage appropriately.
Management of fluid overload and heart failure may require discontinuation of SKYCLARYS.
Lipid Abnormalities: Treatment with SKYCLARYS can cause changes in cholesterol. In the
pivotal study, 29% of patients treated with SKYCLARYS reported elevated cholesterol above ULN at one or
more time points. Mean increases were observed within 2 weeks of initiation of SKYCLARYS and returned to
baseline within 4 weeks of discontinuing treatment. A total of 16% of patients treated with SKYCLARYS had
an increase in low-density lipoprotein cholesterol (LDL-C) from baseline, compared to 8% of patients who
received placebo. The mean increase in LDL-C for all SKYCLARYS-treated patients was 23.5 mg/dL at 48
weeks. A total of 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. The mean decrease in
HDL-C for all SKYCLARYS-treated patients was 5.3 mg/dL at 48 weeks.
Assess lipid parameters prior to initiation of SKYCLARYS and monitor periodically during treatment.
Manage lipid abnormalities according to clinical guidelines.
Adverse reactions reported in 10% or more of patients and greater than placebo were elevated liver
enzymes (AST/ALT) (37%), headache (37%), nausea (33%), abdominal pain (29%), fatigue (24%), diarrhea
(20%), musculoskeletal pain (20%), oropharyngeal pain (18%), influenza (16%), vomiting (16%), muscle
spasms (14%), back pain (13%), decreased appetite (12%), rash (10%).
- Moderate or Strong CYP3A4 Inhibitors: Avoid concomitant use. Consider SKYCLARYS dosage reduction with
monitoring if use is unavoidable.
- Moderate or Strong CYP3A4 Inducers: Avoid concomitant use.
- Hormonal Contraceptives: Counsel females to use an alternative contraceptive method (e.g.,
non-hormonal intrauterine system) or additional non-hormonal contraceptive (e.g., condoms) during
concomitant use and for 28 days after discontinuation of SKYCLARYS.
This is not a complete list of potential drug interactions.
Specific Population: The effects on milk production and the breastfed infant are
unknown. The developmental and health benefits of breastfeeding should be considered along with the
mother’s clinical need for SKYCLARYS and any potential adverse effects on the breastfed infant from
SKYCLARYS or from the underlying maternal condition.
To report SUSPECTED ADVERSE REACTIONS, contact Reata Pharmaceuticals, Inc. at 1-800-314-3934 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
SKYCLARYS is indicated for the treatment of Friedreich ataxia in adults and adolescents aged 16 years
For more information about SKYCLARYS, please see the full Prescribing