Isturisa 1mg Tablets
It is used to treat Cushing's disease.
Drug Class
Cortisol synthesis inhibitor
Pharmacologic Class
11β-hydroxylase inhibitor
Pregnancy Category
Not available
FDA Approved
Mar 2020
DEA Schedule
Not Controlled
Overview
What is this medicine?
Isturisa is a medication used to treat adults with Cushing's disease who cannot undergo or have not responded to pituitary surgery. It works by blocking an enzyme in your body that makes cortisol, a hormone that is too high in people with Cushing's disease. By lowering cortisol levels, Isturisa helps to reduce the symptoms of the disease.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. You can take this medication with or without food.
Storing and Disposing of Your Medication
Keep your medication at room temperature in a dry location, avoiding the bathroom. It's essential to store all medications in a safe place, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, skip it and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. You can take this medication with or without food.
Storing and Disposing of Your Medication
Keep your medication at room temperature in a dry location, avoiding the bathroom. It's essential to store all medications in a safe place, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, skip it and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take Isturisa exactly as prescribed by your doctor, usually twice a day, with or without food.
- Do not stop taking Isturisa suddenly without talking to your doctor, as this can lead to serious side effects (adrenal crisis).
- Carry a medical alert card or wear a medical alert bracelet stating that you are taking Isturisa, especially in case of an emergency.
- Report any signs of adrenal insufficiency (e.g., severe fatigue, nausea, vomiting, dizziness, low blood pressure) to your doctor immediately.
- Report any signs of low potassium (e.g., muscle weakness, cramps, palpitations) to your doctor.
- Regular blood tests and ECGs will be needed to monitor your cortisol levels, electrolytes, and heart rhythm.
- Discuss with your doctor how to manage stress or illness, as you may need a temporary increase in your cortisol replacement (stress dose) if you are also on glucocorticoid replacement.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 2 mg orally twice daily. Titrate by 2 mg twice daily every 2 weeks based on cortisol levels. Max 30 mg twice daily.
Dose Range:
2 - 30 mg
Condition-Specific Dosing:
Cushing's Disease:
Initial 2 mg orally twice daily. Titrate based on urinary free cortisol (UFC) and clinical response. Doses can be increased by 2 mg twice daily, no more frequently than every 2 weeks. Maximum recommended dose is 30 mg twice daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
Not studied in severe renal impairment (eGFR < 30 mL/min/1.73 m2) or end-stage renal disease (ESRD). Use with caution.
Dialysis:
Not studied in patients on dialysis. Use with caution.
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A).
Moderate:
Initial 2 mg once daily. Maximum recommended dose is 10 mg twice daily (Child-Pugh B).
Severe:
Initial 1 mg once daily. Maximum recommended dose is 5 mg twice daily (Child-Pugh C).
Confidence:
High
Pharmacology
Mechanism of Action
Osilodrostat is a steroid 11β-hydroxylase inhibitor. It inhibits 11β-hydroxylase (CYP11B1), an enzyme responsible for the final step of cortisol synthesis in the adrenal cortex. By inhibiting CYP11B1, osilodrostat reduces cortisol production, leading to a decrease in urinary free cortisol (UFC) and plasma cortisol levels in patients with Cushing's disease.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (oral absorption is good)
Tmax:
1 hour (median)
FoodEffect:
A high-fat meal decreases Cmax by 20% and AUC by 15%. Can be taken with or without food.
Distribution:
Vd:
100 L
ProteinBinding:
96% (primarily to albumin)
CnssPenetration:
Limited (crosses blood-brain barrier in animal studies)
Elimination:
HalfLife:
4 hours
Clearance:
Not available
ExcretionRoute:
Primarily feces (91%), minor renal (5%)
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Rapid (within hours of first dose, cortisol reduction observed)
PeakEffect:
Not precisely defined for chronic cortisol reduction, but peak plasma concentration is at 1 hour.
DurationOfAction:
Sustained cortisol reduction with twice-daily dosing.
Confidence:
Medium
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: 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
Signs of low potassium levels: muscle pain or weakness, muscle cramps, or an irregular heartbeat
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision
Signs of a urinary tract infection (UTI): blood in the urine, burning or pain while urinating, frequent or urgent need to urinate, fever, lower abdominal pain, or pelvic pain
Swelling
Unusual hair growth
Pimples (acne)
Depression
This medication can cause a rare but serious condition characterized by very low cortisol levels, which may lead to low blood pressure, electrolyte problems, low blood sugar, or life-threatening adrenal gland problems. If you experience any of the following symptoms, contact your doctor right away:
Severe stomach pain, nausea, or vomiting
Dizziness or fainting
Fast or irregular heartbeat
Headache
Mood changes
Confusion
Muscle pain or weakness
Seizures
Shakiness
Sweating
Excessive sleepiness, tiredness, or weakness
Changes in appetite
Additionally, this medication can cause a type of abnormal heartbeat (prolonged QT interval). If you experience any of the following symptoms, contact your doctor immediately:
Fast heartbeat
Irregular heartbeat
Fainting
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to contact your doctor if you notice any of the following symptoms or if they persist or bother you:
Feeling tired or weak
Diarrhea, nausea, or vomiting
Stomach pain or heartburn
Headache
Nose or throat irritation
Joint pain
Back pain
Cough
Flu-like symptoms
Trouble sleeping
Anxiety
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have any questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: 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
Signs of low potassium levels: muscle pain or weakness, muscle cramps, or an irregular heartbeat
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision
Signs of a urinary tract infection (UTI): blood in the urine, burning or pain while urinating, frequent or urgent need to urinate, fever, lower abdominal pain, or pelvic pain
Swelling
Unusual hair growth
Pimples (acne)
Depression
This medication can cause a rare but serious condition characterized by very low cortisol levels, which may lead to low blood pressure, electrolyte problems, low blood sugar, or life-threatening adrenal gland problems. If you experience any of the following symptoms, contact your doctor right away:
Severe stomach pain, nausea, or vomiting
Dizziness or fainting
Fast or irregular heartbeat
Headache
Mood changes
Confusion
Muscle pain or weakness
Seizures
Shakiness
Sweating
Excessive sleepiness, tiredness, or weakness
Changes in appetite
Additionally, this medication can cause a type of abnormal heartbeat (prolonged QT interval). If you experience any of the following symptoms, contact your doctor immediately:
Fast heartbeat
Irregular heartbeat
Fainting
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to contact your doctor if you notice any of the following symptoms or if they persist or bother you:
Feeling tired or weak
Diarrhea, nausea, or vomiting
Stomach pain or heartburn
Headache
Nose or throat irritation
Joint pain
Back pain
Cough
Flu-like symptoms
Trouble sleeping
Anxiety
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have any questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe fatigue or weakness
- Nausea, vomiting, or abdominal pain
- Dizziness or lightheadedness (especially when standing up)
- Low blood pressure
- Muscle weakness or cramps
- Heart palpitations or irregular heartbeat
- Unexplained weight loss
- Confusion or changes in mental status
- Swelling in the hands, ankles, or feet
- Headache that is severe or persistent
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including low levels of potassium or magnesium in your blood.
Additionally, if you are breast-feeding, please note that you should not breast-feed while taking this medication and for 1 week after your last dose.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Your complete medical history, including any health problems you have
This information will help your doctor determine if it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including low levels of potassium or magnesium in your blood.
Additionally, if you are breast-feeding, please note that you should not breast-feed while taking this medication and for 1 week after your last dose.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Your complete medical history, including any health problems you have
This information will help your doctor determine if it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Regular blood tests will be necessary, as directed by your doctor. Be sure to discuss any concerns or questions you have with your doctor.
Before starting this medication and throughout treatment, you will need to undergo an electrocardiogram (ECG) to monitor your heart activity. Discuss the details with your doctor.
Your doctor may also require you to have your urine checked regularly. Follow the schedule recommended by your doctor.
You may need to take extra potassium supplements while taking this medication. Consult with your doctor to determine if this is necessary for you.
If you are pregnant or planning to become pregnant, inform your doctor immediately. You and your doctor will need to discuss the potential benefits and risks of using this medication during pregnancy to make an informed decision.
Regular blood tests will be necessary, as directed by your doctor. Be sure to discuss any concerns or questions you have with your doctor.
Before starting this medication and throughout treatment, you will need to undergo an electrocardiogram (ECG) to monitor your heart activity. Discuss the details with your doctor.
Your doctor may also require you to have your urine checked regularly. Follow the schedule recommended by your doctor.
You may need to take extra potassium supplements while taking this medication. Consult with your doctor to determine if this is necessary for you.
If you are pregnant or planning to become pregnant, inform your doctor immediately. You and your doctor will need to discuss the potential benefits and risks of using this medication during pregnancy to make an informed decision.
Overdose Information
Overdose Symptoms:
- Exaggerated signs of hypocortisolism (e.g., severe hypotension, profound fatigue, vomiting, abdominal pain)
- Electrolyte disturbances (e.g., severe hypokalemia)
- QT prolongation
What to Do:
There is no specific antidote for osilodrostat overdose. Management should be supportive and symptomatic. Monitor for signs of adrenal insufficiency, hypokalemia, and QT prolongation. Administer glucocorticoid replacement if adrenal insufficiency is suspected. Correct electrolyte imbalances. Consider activated charcoal if ingestion is recent. Contact a poison control center (e.g., 1-800-222-1222) for further guidance.
Drug Interactions
Contraindicated Interactions
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) due to significant decrease in osilodrostat exposure and potential loss of efficacy.
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) may increase osilodrostat exposure, requiring dose adjustment of osilodrostat.
- Drugs that prolong the QT interval (e.g., Class IA and Class III antiarrhythmics, antipsychotics, macrolide antibiotics, fluoroquinolones) due to additive risk of QT prolongation.
Moderate Interactions
- Moderate CYP3A4 inducers (e.g., efavirenz, bosentan) may decrease osilodrostat exposure.
- Moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, fluconazole) may increase osilodrostat exposure.
- Substrates of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and UGT1A1 (osilodrostat is a weak inhibitor of these enzymes, potentially increasing exposure of sensitive substrates).
Minor Interactions
- Not specifically listed, but general caution with drugs metabolized by or affecting the aforementioned enzymes.
Monitoring
Baseline Monitoring
24-hour Urinary Free Cortisol (UFC)
Rationale: To establish baseline cortisol levels and guide initial dosing.
Timing: Prior to initiation of therapy.
Serum Electrolytes (especially potassium)
Rationale: To assess baseline electrolyte balance, as osilodrostat can cause hypokalemia.
Timing: Prior to initiation of therapy.
Electrocardiogram (ECG)
Rationale: To assess baseline QTc interval and identify risk factors for QT prolongation.
Timing: Prior to initiation of therapy.
Blood Pressure
Rationale: To establish baseline and monitor for changes, as osilodrostat can affect blood pressure.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function, especially important for dose adjustments in hepatic impairment.
Timing: Prior to initiation of therapy.
Renal Function Tests
Rationale: To assess baseline renal function.
Timing: Prior to initiation of therapy.
Routine Monitoring
24-hour Urinary Free Cortisol (UFC)
Frequency: Weekly or bi-weekly during dose titration, then periodically (e.g., monthly or every 3-6 months) once stable.
Target: Normalization of UFC or clinical improvement.
Action Threshold: Adjust dose based on UFC levels and clinical signs/symptoms of hypercortisolism or hypocortisolism.
Serum Electrolytes (especially potassium)
Frequency: Weekly or bi-weekly during dose titration, then periodically (e.g., monthly or every 3-6 months) once stable.
Target: Within normal limits (e.g., K+ 3.5-5.0 mEq/L).
Action Threshold: Supplement potassium if hypokalemic; consider dose reduction or discontinuation if severe or persistent.
Blood Pressure
Frequency: Regularly (e.g., weekly during titration, then monthly).
Target: Individualized, aiming for normotension.
Action Threshold: Manage hypertension with antihypertensives or consider osilodrostat dose adjustment.
Electrocardiogram (ECG)
Frequency: Periodically, especially if risk factors for QT prolongation are present or if symptoms of arrhythmia occur.
Target: QTc < 450 ms (men), < 470 ms (women).
Action Threshold: If QTc prolongation occurs, correct electrolyte abnormalities, consider dose reduction or discontinuation, and avoid concomitant QT-prolonging drugs.
Signs and Symptoms of Adrenal Insufficiency
Frequency: Continuously (patient education is key).
Target: Absence of symptoms.
Action Threshold: If symptoms occur (e.g., fatigue, nausea, vomiting, hypotension), measure serum cortisol and initiate glucocorticoid replacement if needed. Consider osilodrostat dose reduction or temporary interruption.
Symptom Monitoring
- Symptoms of hypocortisolism/adrenal insufficiency (e.g., severe fatigue, weakness, nausea, vomiting, abdominal pain, dizziness, hypotension, weight loss)
- Symptoms of hypokalemia (e.g., muscle weakness, cramps, palpitations, constipation)
- Symptoms of QT prolongation/arrhythmia (e.g., palpitations, dizziness, syncope)
- Symptoms of hypercortisolism (if dose is too low or missed doses, e.g., weight gain, easy bruising, muscle weakness, mood changes)
- Headache
- Nausea
- Diarrhea
- Peripheral edema
Special Patient Groups
Pregnancy
Osilodrostat may cause fetal harm when administered to a pregnant woman. Based on animal studies, it is not recommended for use during pregnancy. Females of reproductive potential should be advised of the potential risk to a fetus and use effective contraception during treatment and for at least one week after the last dose.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm based on animal data (embryo-fetal toxicity, teratogenicity).
Second Trimester:
Potential for fetal harm based on animal data.
Third Trimester:
Potential for fetal harm based on animal data.
Lactation
It is not known whether osilodrostat or its metabolites are excreted in human milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment with Isturisa and for at least one week after the last dose.
Infant Risk:
Potential for serious adverse reactions (e.g., adrenal suppression, growth inhibition) in breastfed infants. Risk is unknown but considered high due to drug's mechanism of action.
Pediatric Use
The safety and effectiveness of Isturisa in pediatric patients have not been established.
Geriatric Use
No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger patients. However, greater sensitivity of some older individuals cannot be ruled out. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Clinical Information
Clinical Pearls
- Osilodrostat is a potent cortisol synthesis inhibitor; careful titration is crucial to avoid hypocortisolism and adrenal insufficiency.
- Patients should be educated on the signs and symptoms of adrenal insufficiency and instructed to seek immediate medical attention if they occur.
- Regular monitoring of 24-hour UFC, serum potassium, and blood pressure is essential, especially during dose titration.
- Hypokalemia is a common side effect and should be managed promptly with potassium supplementation.
- ECG monitoring for QTc prolongation is important, particularly in patients with pre-existing cardiac conditions or those on other QT-prolonging medications.
- Strong CYP3A4 inducers are contraindicated due to significant reduction in osilodrostat exposure and potential loss of efficacy.
- Patients should carry a medical alert card indicating they are on Isturisa and the need for potential stress dose glucocorticoid replacement in emergencies.
Alternative Therapies
- Pituitary surgery (transsphenoidal adenomectomy) - often first-line treatment for Cushing's disease.
- Bilateral adrenalectomy (surgical removal of adrenal glands) - for severe or refractory cases.
- Pasireotide (Signifor, Signifor LAR) - somatostatin analog.
- Mifepristone (Korlym) - glucocorticoid receptor blocker.
- Ketoconazole (off-label use) - antifungal with cortisol synthesis inhibiting properties.
- Metyrapone (Metopirone) - 11β-hydroxylase inhibitor (not FDA approved in US for Cushing's disease).
- Cabergoline (off-label use) - dopamine agonist.
- Radiation therapy (e.g., stereotactic radiosurgery) - for pituitary tumors.
Cost & Coverage
Average Cost:
Highly variable, typically >$20,000 - $30,000+ per 60 tablets (e.g., 1mg, 5mg, 10mg, 25mg)
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to step therapy and quantity limits)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication, including the amount taken and the time it happened, to help healthcare professionals provide the best possible care.