Medically reviewed by Drugs.com. Last updated on Oct 11, 2020.
(oh SIL oh DROE stat)
- Osilodrostat Phosphate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Isturisa: 1 mg, 5 mg, 10 mg
Brand Names: U.S.
- Cortisol Synthesis Inhibitor
Osilodrostat decreases cortisol synthesis via inhibition of 11beta-hydroxylase (CYP11B1), the enzyme responsible for the final step of cortisol biosynthesis in the adrenal gland.
Vd: ~100 L.
Hepatically metabolized by multiple CYP enzymes (eg, CYP3A4, CYP2B6, CYP2D6) and UDP-glucuronosyltransferases to inactive metabolites; no single enzyme contributes >25% to the total clearance.
Urine: 90.6% (5.2% as unchanged drug); feces: 1.58%.
Time to Peak
Use: Labeled Indications
Cushing disease: Treatment of Cushing disease in adults for whom pituitary surgery is not an option or has not been curative.
There are no contraindications listed in the manufacturer's labeling.
Note: Correct hypokalemia and hypomagnesemia prior to initiating therapy. Obtain baseline ECG; repeat ECG within 1 week after treatment initiation, and as clinically indicated thereafter.
Cushing disease: Oral: Initial: 2 mg twice daily. Titrate by 1 to 2 mg twice daily no more frequently than every 2 weeks according to rate of cortisol changes, tolerability, and clinical response. If patient tolerates a dosage of 10 mg twice daily but cortisol target is not achieved, dosage may be increased by 5 mg twice daily every 2 weeks; typical maintenance dosage: 2 to 7 mg twice daily (maximum: 30 mg twice daily).
Refer to adult dosing.
Oral: May be administered with or without food.
Store at room temperature between 20°C to 25°C (68°F to 77°F); excursions permitted 15°C to 30°C (59°F to 86°F); protect from moisture.
CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Weak) may increase the serum concentration of CloBAZam. Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Osilodrostat. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Osilodrostat. Management: Reduce osilodrostat dose by 50% during coadministration with a strong CYP3A4 inhibitor. Consider therapy modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Monitor therapy
Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Cardiovascular: Edema (7% to 21%), hypertension (10% to 14%), hypotension (12%)
Dermatologic: Acne vulgaris (9% to 11%), skin rash (15%)
Endocrine & metabolic: Adrenocortical insufficiency (43%), altered hormone level (12%; corticotrophin increased: 14%), decreased cortisol (18% to 31%), hirsutism (10% to 12%), hypokalemia (12% to 17%), increased testosterone level (11%)
Gastrointestinal: Abdominal pain (13%), decreased appetite (12%), diarrhea (15%), nausea (37%), vomiting (19%)
Genitourinary: Urinary tract infection (12%)
Hematologic & oncologic: Benign neoplasm (decrease in pituitary corticotroph tumor volume >20%: 18%), tumor growth (increase in pituitary corticotroph tumor volume >20%: 15%; no correlation between tumor volume and increase in adrenocorticotrophic hormone)
Nervous system: Dizziness (14%), fatigue (39%), headache (31%)
Neuromuscular & skeletal: Arthralgia (18%), back pain (15%), myalgia (12%)
Respiratory: Nasopharyngitis (20%)
Miscellaneous: Fever (11%)
1% to 10%:
Cardiovascular: Prolonged QT interval on ECG (4%), syncope (2%), tachycardia (7%)
Dermatologic: Alopecia (6%)
Gastrointestinal: Dyspepsia (8%), gastroenteritis (7%)
Hematologic & oncologic: Anemia (10%), neutropenia (1%)
Hepatic: Increased serum transaminases (4%)
Infection: Influenza (10%)
Nervous system: Anxiety (7%), depression (7%), insomnia (8%), malaise (7%)
Respiratory: Cough (10%)
Concerns related to adverse effects:
• Adrenal insufficiency/hypocortisolism: Decrease dosage or temporarily discontinue therapy if urine free cortisol levels fall below the target range, there is a rapid decrease in cortisol levels, and/or symptoms of hypocortisolism (eg, anorexia, fatigue, hypoglycemia, hyponatremia, hypotension, nausea, vomiting, weakness) occur; glucocorticoid replacement therapy should be initiated if necessary. Discontinue therapy and administer glucocorticoid replacement therapy if serum or plasma cortisol levels are below target range and patient has symptoms of adrenal insufficiency; cortisol suppression may persist beyond the 4-hour half-life of osilodrostat. If treatment is interrupted, reinitiate at a lower dose when cortisol levels are within target ranges and symptoms have resolved.
• Altered cardiac conduction: Use has been associated with a dose-dependent QT interval prolongation (maximum mean estimated QTcF increase of up to 5.3 msec at 30 mg), which may cause cardiac arrhythmias. Obtain a baseline QTc interval measurement prior to initiating and monitor QTc interval during therapy; consider temporary discontinuation for QTc interval >480 msec. Correct hypokalemia and/or hypomagnesemia prior to initiation and monitor periodically during therapy. Use caution in patients with risk factors for QT prolongation (eg, congenital long QT syndrome, congestive heart failure, bradyarrhythmias, concomitant QT-prolonging medications) and consider more frequent ECG monitoring.
• Androgenic effects: Use may increase circulating androgen levels, which may lead to hirsutism, hypertrichosis, and acne (in females).
• Edema: Edema may occur due to increased levels of aldosterone precursors; monitor for worsening edema.
• Hypertension: Hypertension may occur due to increased levels of aldosterone precursors; monitor for worsening of hypertension.
• Hypokalemia: Hypokalemia may occur due to increased levels of aldosterone precursors. Correct hypokalemia prior to initiating therapy and monitor potassium during therapy. Potassium supplementation and/or use of a mineralocorticoid antagonist may be required; if hypokalemia persists, dose reduction or discontinuation of osilodrostat may be necessary.
Cortisol levels (initially from at least two 24-hour urine free cortisol collections every 1 to 2 weeks until adequate clinical response is maintained, then at least every 1 to 2 months or as indicated); use caution in interpreting urine free cortisol levels in patients with moderate to severe renal impairment due to reduced urine free cortisol excretion; consider using methods other than urinary free cortisol levels for cortisol monitoring (Braun 2019).
Serum potassium and magnesium (prior to initiation and periodically thereafter); ECG (baseline, after 1 week, and as clinically indicated thereafter); BP; signs of edema. Signs and symptoms of adrenal insufficiency (eg, anorexia, fatigue, hypoglycemia, hyponatremia, hypotension, nausea, vomiting, weakness); monitor more frequently in patients with hepatic impairment.
Adverse events were not observed in animal reproduction studies.
What is this drug used for?
• It is used to treat Cushing disease.
Frequently reported side effects of this drug:
• Loss of strength and energy
• Abdominal pain
• Nose irritation
• Throat irritation
• Joint pain
• Back pain
• Flu-like signs
• Trouble sleeping
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat
• Urinary tract infection like hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain
• Severe headache
• Passing out
• Vision changes
• Hair growth
• Fast heartbeat
• Abnormal heartbeat
• Low cortisol levels like severe abdominal pain, nausea, vomiting, dizziness, passing out, fast heartbeat, abnormal heartbeat, headache, mood changes, confusion, muscle pain, muscle weakness, seizures, tremors, sweating, severe fatigue, increased appetite, or lack of appetite
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
More about osilodrostat
- Side Effects
- During Pregnancy
- Dosage Information
- Drug Interactions
- En Español
- Drug class: adrenal corticosteroid inhibitors
- Other brands
Related treatment guides
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