omaveloxolone
Skyclarys
Pharmaceutical company: Reata Pharmaceuticals
Pharmacologic classification:Nuclear factor(erythroid-derived 2) activator
Therapeutic classification:Miscellaneous CNS drug
AVAILABLE FORMS
Capsules: 50 mg
INDICATIONS AND DOSAGES
Friedreich ataxia
Adults and adolescents age 16 and older: 150 mg PO once daily on an empty stomach at least 1 hour before a meal.
Adjust-a-dose: If use with a strong CYP3A4 inhibitor can't be avoided, reduce omaveloxolone to 50 mg once daily. If use with a moderate CYP3A4 inhibitor can't be avoided, or for patients with Child-Pugh class B liver impairment, reduce omaveloxolone to 100 mg once daily. If adverse reactions develop, further decrease dose to 50 mg once daily. Discontinue if adverse reactions occur at 50 mg dose.
CONTRAINDICATIONS AND CAUTIONS
- May worsen cardiac function. Use cautiously in patients with heart failure or cardiac disease.
- Avoid use in Child-Pugh class C liver impairment.
- Safety and effectiveness have not been established in children younger than age 16.
- Dialyzable drug: Unknown.
PREGNANCY-LACTATION-REPRODUCTION
- Based on animal data, this drug may cause fetal harm.
- There are no data on presence of this drug in human milk. Effects on milk production and the breastfed infant are unknown. Use only if the benefit to the patient outweighs the risk to the infant.
- May decrease efficacy of hormonal contraceptives. Patients of childbearing potential should use an alternative contraceptive method or additional nonhormonal contraceptive (condoms) during concomitant use and for 28 days after discontinuation of omaveloxolone.
INTERACTIONS
Drug-drug. CYP3A4 substrates (midazolam), CYP2C8 substrates (repaglinide),
BCRP and OATP1B1 substrates (rosuvastatin):
May decrease level of substrate drug. Monitor for lack of efficacy.
Hormonal contraceptives (pill, patch, ring, implant, and progestin-only pill): May decrease contraceptive effectiveness. Avoid concomitant use.
Strong or moderate CYP3A4 inducers: May decrease omaveloxolone level and its effectiveness. Avoid concomitant use.
Strong or moderate CYP3A4 inhibitors: May increase omaveloxolone level. Avoid concomitant use. If use can't be avoided, reduce omaveloxolone dose.
Drug-herb. St. John's wort: May decrease omaveloxolone level. Avoid concomitant use.
Drug-food. Grapefruit, grapefruit juice: May increase omaveloxolone level. Discourage concomitant use.
ADVERSE REACTIONS
CNS: headache, fatigue.
CV: increased B-type natriuretic peptide.
EENT: oropharyngeal pain.
GI: nausea, diarrhea, vomiting, abdominal pain, decreased appetite.
Hepatic: increased liver enzymes.
Metabolic: increased LDL-cholesterol, decreased HDL-cholesterol.
Musculoskeletal: musculoskeletal pain, spasms, back pain.
Skin: rash.
Other: flulike syndrome.
Reactions in bold italics are life-threatening.
Released: June 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer
sparsentan
Filspari
Pharmaceutical company: Travere Therapeutics
Pharmacologic classification: Endothelin and angiotensin II receptor antagonist
Therapeutic classification: Miscellaneous GU drug
AVAILABLE FORMS
Tablets: 200 mg, 400 mg
INDICATIONS AND DOSAGES
Reduce proteinuria in patients with primary immunoglobulin A nephropathy at risk for rapid disease progression
Adults: 200 mg PO once daily. After 14 days, increase to 400 mg PO once daily, as tolerated. Consider repeating titration when resuming drug after an interruption.
Adjust-a-dose: Refer to the manufacturer's instructions for dosage adjustment and monitoring in patients developing transaminase elevations of more than
3 times the upper limit of normal (ULN). If treatment is withheld, don't resume in patients with symptoms of liver toxicity or liver enzyme levels and bilirubin that have not returned to pretreatment levels. Stop the drug permanently if ALT or AST is greater than 8 x ULN and no other cause is found.
CONTRAINDICATIONS AND CAUTIONS
- Black Box Warning: Prescribers, patients, and pharmacies must enroll in a REMS program due to risks of elevation in aminotransferases, hepatotoxicity and liver failure, and major birth defects.
- Alert: Avoid use in patients with any degree of liver impairment, including those with aminotransferase levels greater than 3 x ULN at baseline.
- This drug inhibits the renin-angiotensin-aldosterone system (RAAS) and may increase the risk of acute kidney injury.
- Use cautiously in those at risk for hypotension, in those with fluid retention, and in patients with advanced kidney disease, due to the risk of hyperkalemia. Use hasn't been evaluated in patients with heart failure.
- Safety and effectiveness in children haven't been established.
- Dialyzable drug: Unlikely.
PREGNANCY-LACTATION-REPRODUCTION
- Black Box Warning: Use during pregnancy is contraindicated. This drug can cause major birth defects and fetal death if used during pregnancy. Initiate in patients of childbearing potential only after confirmation of a negative pregnancy test. Pregnancy testing is also required monthly during treatment, and one month after discontinuation.
- Patients who can become pregnant must use effective contraception before initiation, monthly during treatment, and for one month after discontinuation.
- Breastfeeding isn't recommended during treatment due to the risk of adverse reactions, such as hypotension, in breastfed infants.
INTERACTIONS
Drug-drug. Antacids and acid-reducing agents (histamine-2 [H2] antagonists, PPI): May decrease sparsentan level. Administer sparsentan 2 hours before or after antacids. Avoid concomitant use with H2 antagonists and PPIs.
CYP2B6, 2C9, 2C19 substrates (bupropion): May decrease substrate level.
Drugs that increase serum potassium (potassium-sparing diuretics, potassium supplements): May increase risk of hyperkalemia. Monitor potassium level.
Monitor for substrate efficacy and consider dosage adjustment.
Moderate CYP3A inhibitors (cyclosporine): May increase sparsentan level and the risk of adverse reactions. Monitor blood pressure, edema, potassium, and kidney function.
NSAIDs (cyclooxygenase-2 inhibitors): May worsen kidney function. Monitor for signs of worsening kidney function.
P-gp substrates (fexofenadine, digoxin) and BCRP substrates (glyburide, cimetidine, rosuvastatin): May increase substrate level and substrate-related adverse reactions. Avoid concomitant use of sensitive substrates.
Alert: RAAS inhibitors (angiotensin receptor blockers, ACE inhibitors), endothelin receptor antagonists (bosentan, ambrisentan), aliskiren: May increase risk of hypotension, syncope, hyperkalemia, and decreased kidney function. Use together is contraindicated.
Strong CYP3A inducers (rifampin): May decrease sparsentan level. Avoid use together.
Strong CYP3A inhibitors (itraconazole): May increase sparsentan level. Avoid use together. If not possible, interrupt sparsentan.
Drug-food. Potassium-containing salt substitutes: May cause hyperkalemia. Monitor potassium level.
ADVERSE REACTIONS
CNS: dizziness.
CV: peripheral edema, hypotension, orthostatic hypotension.
GU: acute kidney injury.
Hematologic: anemia.
Hepatic: transaminase elevations.
Metabolic: hyperkalemia.
Reactions in bold italics are life-threatening.
Released: June 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer