Brand Name
Isturisa
Generic Name
Osilodrostat
View Brand Information FDA approval date: March 31, 2020
Classification: Cortisol Synthesis Inhibitor
Form: Tablet
What is Isturisa (Osilodrostat)?
ISTURISA is indicated for the treatment of endogenous hypercortisolemia in adults with Cushing's syndrome for whom surgery is not an option or has not been curative. ISTURISA is a cortisol synthesis inhibitor indicated for the treatment of endogenous hypercortisolemia in adults with Cushing's syndrome for whom surgery is not an option or has not been curative
Approved To Treat
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Brand Information
Isturisa (Osilodrostat)
1INDICATIONS AND USAGE
ISTURISA is indicated for the treatment of endogenous hypercortisolemia in adults with Cushing's syndrome for whom surgery is not an option or has not been curative.
2DOSAGE FORMS AND STRENGTHS
ISTURISA is available as:
- 1 mg tablets: Pale yellow, unscored, round, biconvex with beveled edge tablet, debossed "1" on one side.
- 5 mg tablets: Yellow, unscored, round, biconvex with beveled edge tablet, debossed "5" on one side.
3CONTRAINDICATIONS
None.
4ADVERSE REACTIONS
Clinically significant adverse reactions that appear in other sections of the labeling include:
- Hypocortisolism
- QT Prolongation
- Elevations in Adrenal Hormone Precursors and Androgens
4.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
The safety of ISTURISA was evaluated in two clinical trials in adults with Cushings disease. Study 1 (NCT02180217) was a 4-period, multicenter study with a 12-week open-label titration period, 12-week open-label maintenance period, 8-week double-blind, placebo-controlled period, and 14 to 24-week open label treatment period in 137 patients with Cushing's disease. Study 2 (NCT02697734) was a 2-period, multicenter study with a 12-week randomized, double-blind, placebo-controlled period and a 36-week open-label treatment period in 74 patients with Cushing's disease
4.2Postmarketing Experience
Additional adverse reactions have been identified during postapproval use of ISTURISA. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Neutropenia associated with fever and infection
5OVERDOSAGE
Overdosage may result in severe hypocortisolism. Signs and symptoms suggestive of hypocortisolism may include nausea, vomiting, fatigue, low blood pressure, abdominal pain, loss of appetite, dizziness, and syncope.
In case of suspected overdosage, ISTURISA should be temporarily discontinued, cortisol levels should be checked, and if necessary, corticosteroid supplementation should be initiated. Close surveillance may be necessary, including monitoring of the QT interval, blood pressure, glucose, fluid, and electrolyte until the patient's condition is stable.
6DESCRIPTION
ISTURISA (osilodrostat) is a cortisol synthesis inhibitor.
The chemical name of osilodrostat is 4-[(5
Molecular formula of osilodrostat salt (phosphate) form on anhydrous basis is: (C
ISTURISA tablets for oral administration contains 1 mg or 5 mg of osilodrostat equivalent to 1.4 mg or 7.2 mg of osilodrostat phosphate respectively, and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, mannitol, microcrystalline cellulose, and magnesium stearate. The film coat is composed of hypromellose, titanium dioxide, ferric oxide (yellow), ferric oxide (red) (1 mg only), polyethylene glycol 4000, and talc.
7CLINICAL STUDIES
The safety and efficacy of ISTURISA was evaluated in 2 multicenter clinical studies, Study 1 (NCT02180217) and Study 2 (NCT02697734), in adults with persistent or recurrent Cushing's disease despite pituitary surgery or de novo patients for whom surgery was not indicated or who had refused surgery. Study 1 was a 48-week study that included an 8-week, double-blind, randomized withdrawal period at Weeks 26 to 34 in the study. After Week 48, patients who maintained clinical benefit on ISTURISA could continue in a long-term extension period until the last patient reached Week 72. Study 2 was a 48-week study in which patients were randomized 2:1 to ISTURISA or placebo and treated for 12 weeks followed by a 36-week open-label treatment. After completion of week 48, patients who maintained clinical benefit on ISTURISA could continue on ISTURISA in an optional 48-week extension period.
7.1Study 1
The safety and efficacy of ISTURISA was assessed in a 48-week, multicenter study (called the Core Period) that consisted of four study periods as follows:
- Period 1: 12-week, open-label, dose titration period
- Period 2: 12-week, open-label, maintenance treatment period
- Period 3: 8-week, double-blind, placebo-controlled, randomized withdrawal treatment period which provided the data for the primary efficacy endpoint
- Period 4: open-label treatment period of 14 to 24 weeks duration
The mean age at enrollment was 41 years; 77% of patients were female. There were 65% Caucasian, 28% Asian, 3% black, and 4% other race. Overall, 96% patients had received previous treatments for Cushing's disease prior to entering the study, of which 88% had undergone surgery. Persistence or recurrence of Cushing's disease was evidenced by the mean of three 24-hour UFC (mUFC) > 1.5× upper limit of normal (ULN). The mean mUFC (SD) at baseline was 1006 nmol/24 hr (1589) (365 mcg/24 hr), which corresponds to approximately 7 × ULN. The median mUFC at baseline was 476 nmol/24 hr (173 mcg/24 hr), which corresponds to approximately 3.5 × ULN.
7.2Study 2
The safety and efficacy of ISTURISA was assessed in a 48-week, multicenter study that consisted of two core study periods as follows:
- Period 1: 12-week, double-blind, placebo-controlled, randomized treatment period with ISTURISA or placebo.
- Period 2: 36-week, open-label, treatment period with ISTURISA.
Study 2 enrolled 74 patients with Cushing's disease, of whom 73 were treated. The mean (range) age at enrollment was 41 (19 to 67) years; 84% were female. There was 67% Caucasian, 23% Asian, 3% black, and 7% other race. Overall, 96% of patients had persistent/recurring Cushing's disease prior to entering the study, of which 88% had undergone previous surgery and 62% of patients had prior medical treatment for Cushing's disease. Persistence or recurrence of Cushing's disease was evidenced by the mean of three 24-hour UFC (mUFC) > 1.3× upper limit of normal (ULN). The mean mUFC (SD) at baseline was 432 nmol/24hr (389) (157 mcg/24 hr), which corresponds to approximately 3.1 × ULN. The median mUFC at baseline was 340 nmol/24hr (123 mcg/24 hr), which corresponds to approximately 2.5 × ULN.
8PATIENT COUNSELING INFORMATION
Advise patients to read the FDA-approved patient labeling (Patient Information).
9PRINCIPAL DISPLAY PANEL - 1 mg Blister Pack Carton
NDC 55292-330-60
Isturisa
Rx only
Each tablet contains 1 mg osilodrostat (as osilodrostat phosphate).
60 film-coated tablets
RECORDATI
10PRINCIPAL DISPLAY PANEL - 5 mg Blister Pack Carton
NDC 55292-331-60
Isturisa
Rx only
Each tablet contains 5 mg osilodrostat (as osilodrostat phosphate).
60 film-coated tablets
RECORDATI
11PRINCIPAL DISPLAY PANEL - 1 mg Blister Pack Carton
NDC 55292-320-60
Isturisa
Rx only
Each tablet contains 1 mg osilodrostat (as osilodrostat phosphate).
60 film-coated tablets
RECORDATI
12PRINCIPAL DISPLAY PANEL - 5 mg Blister Pack Carton
NDC 55292-321-60
Isturisa
Rx only
Each tablet contains 5 mg osilodrostat (as osilodrostat phosphate).
60 film-coated tablets
RECORDATI
13PRINCIPAL DISPLAY PANEL - 10 mg Blister Pack Carton
NDC 55292-322-60
Isturisa
Rx only
Each tablet contains 10 mg osilodrostat (as osilodrostat phosphate).
60 film-coated tablets
RECORDATI
