osilodrostat

Contraindicated in:

Lactation: Lactation.

Use Cautiously in:

Congenital long QT syndrome, HF, bradyarrhythmias, hypokalemia, or hypomagnesemia (↑ risk of QT interval prolongation);
Moderate or severe hepatic impairment (↓ dose);
OB: Safety not established in pregnancy;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, hypotension, hypertension, QT interval prolongation, tachycardia

Derm: rash, acne (females), alopecia, hirsutism, hypertrichosis

EENT: nasopharyngitis

Endo: hypocortisolism, ↑testosterone levels, hypoglycemia

F and E: hypokalemia

GI: abdominal pain, diarrhea, nausea, vomiting, dyspepsia, ↑liver enzymes

GU: urinary tract infection

Hemat: anemia

Metab: ↓appetite

MS: arthralgia, myalgia

Neuro: dizziness, headache, anxiety, depression, insomnia, syncope

Resp: cough

Misc: fatigue, fever

Interactions ⬆ ⬇

Drug-drug:

QT interval prolonging medications may ↑ risk of QT interval prolongation and torsades de pointes.
Strong CYP3A4 inhibitors, including clarithromycin and itraconazole, may ↑ levels and risk of toxicity; ↓ dose of osilodrostat by 50%.
CYP3A4 inducers and CYP2B6 inducers, including carbamazepine, phenobarbital, and rifampin, may ↓ levels and effectiveness; may need to ↑ osilodrostat dose based on urine free cortisol levels.
May ↑ levels and risk of toxicity of CYP1A2 substrates and CYP2C19 substrates with a narrow therapeutic index, including theophylline and tizanidine.

Availability ⬆ ⬇

Tablets: 1 mg; 5 mg

Route/Dosage ⬆ ⬇

PO (Adults ): 2 mg twice daily; may ↑ by 1–2 mg twice daily every 2 wk based on urine free cortisol levels, tolerability, and signs/symptoms. If patient continues to have elevated urine free cortisol levels while taking 10 mg twice daily, may ↑ by 5 mg twice daily every 2 wk (max dose = 30 mg twice daily).

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 1 mg twice daily; may ↑ by 1–2 mg twice daily every 2 wk based on urine free cortisol levels, tolerability, and signs/symptoms. If patient continues to have elevated urine free cortisol levels while taking 10 mg twice daily, may ↑ by 5 mg twice daily every 2 wk (max dose = 30 mg twice daily). Severe hepatic impairment: 1 mg once daily; may ↑ by 1–2 mg twice daily every 2 wk based on urine free cortisol levels, tolerability, and signs/symptoms. If patient continues to have elevated urine free cortisol levels while taking 10 mg twice daily, may ↑ by 5 mg twice daily every 2 wk (max dose = 30 mg twice daily).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits 11-beta-hydroxylase, an enzyme responsible for the final step of cortisol synthesis in the adrenal gland.

Therapeutic effects:

Reduction in urine free cortisol levels.

Classifications ⬆ ⬇

Therapeutic Classification: none assigned

Pharmacologic Classification: cortisol synthesis inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: High-fat meals may delay and reduce extent of absorption.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Metabolized by the CYP3A4, CYP2B6, and CYP2D6 isoenzymes as well as UDP-glucuronosyltransferases. Primarily excreted in urine (91%; 5% as unchanged drug), with minimal excretion in feces.

Half-Life: 4 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1 hr	12 hr

Patient/Family Teaching ⬆ ⬇

Instruct patient to take osilodrostat as directed. Omit missed doses; take next dose at regularly scheduled time. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional if signs and symptoms of low cortisol levels (nausea, abdominal pain, vomiting, loss of appetite, tiredness, dizziness, low blood pressure) occur.
Inform patient of possibility of hyperandrogenism. Advise patient to notify health care professional if signs and symptoms (hirsutism, hypertrichosis, acne in females, swelling of legs and ankles) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during and for 1 wk after final dose.
Emphasize importance of regular lab test to monitor for side effects.

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Indications ⬇

Contraind./Precautions ⬆ ⬇