Isturisa 10mg Tablets
It is used to treat Cushing's disease.
Drug Class
Cortisol Synthesis Inhibitor
Pharmacologic Class
11β-Hydroxylase Inhibitor
Pregnancy Category
D
FDA Approved
Mar 2020
DEA Schedule
Not Controlled
Overview
What is this medicine?
Isturisa is a medication used to treat Cushing's disease. It works by lowering the amount of cortisol, a hormone, that your body makes. Too much cortisol can cause many health problems. By reducing cortisol, Isturisa helps manage the symptoms of Cushing's 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 storage in a bathroom. It's essential to store all medications in a safe place, out of the reach of children and pets, to prevent accidental ingestion.
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 storage in a bathroom. It's essential to store all medications in a safe place, out of the reach of children and pets, to prevent accidental ingestion.
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 you are taking Isturisa, especially if you are at risk for adrenal insufficiency.
- Report any signs of low cortisol (e.g., extreme tiredness, nausea, vomiting, dizziness, low blood pressure) to your doctor immediately.
- Attend all scheduled doctor appointments and laboratory tests (blood tests, urine tests, ECGs) to monitor your cortisol levels and other important health markers.
- Be aware of symptoms of low potassium (muscle weakness, cramps) and report them.
- Avoid grapefruit and grapefruit juice as they may interact with this medication.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose 2 mg orally twice daily. Titrate based on urinary free cortisol (UFC) levels and tolerability. Doses can be increased by 1-2 mg twice daily, up to a maximum of 30 mg twice daily.
Dose Range:
2 - 30 mg
Condition-Specific Dosing:
Cushing's Disease:
Initial 2 mg BID, titrate based on UFC and tolerability. Max 30 mg BID (total 60 mg/day).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed.
Moderate:
No dose adjustment needed.
Severe:
No dose adjustment needed.
Dialysis:
No specific recommendations; not expected to be dialyzable due to high protein binding.
Hepatic Impairment:
Mild:
No dose adjustment needed (Child-Pugh A).
Moderate:
Initial dose 1 mg orally twice daily (Child-Pugh B).
Severe:
Not studied; use is not recommended (Child-Pugh C).
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 this enzyme, osilodrostat reduces cortisol production, leading to decreased circulating cortisol levels.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (oral absorption is good)
Tmax:
Approximately 1 hour
FoodEffect:
High-fat meal decreases Cmax by 25% and AUC by 17%. Can be taken with or without food.
Distribution:
Vd:
Approximately 100 L
ProteinBinding:
Approximately 90%
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 4 hours
Clearance:
Approximately 17 L/hour
ExcretionRoute:
Mainly urine (60%), feces (30%)
Unchanged:
Approximately 10% (urine)
Pharmacodynamics
OnsetOfAction:
Rapid reduction in cortisol levels within hours of first dose.
PeakEffect:
Peak cortisol reduction typically observed within days to weeks of initiating therapy and dose titration.
DurationOfAction:
Due to short half-life, requires twice-daily dosing to maintain effect.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience 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 also cause very low cortisol levels, leading to potentially 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 abnormal 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 right away:
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're bothered by any of the following:
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 is not an exhaustive list of possible side effects. If you have 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, this medication can cause severe and potentially life-threatening side effects. If you experience 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 also cause very low cortisol levels, leading to potentially 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 abnormal 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 right away:
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're bothered by any of the following:
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 is not an exhaustive list of possible side effects. If you have 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 diarrhea
- Dizziness or lightheadedness (especially when standing up)
- Low blood pressure
- Abdominal pain
- Muscle weakness or cramps
- Irregular heartbeat or palpitations
- Unexplained weight loss
- Darkening of the skin
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, to monitor your condition. Be sure to discuss any concerns or questions you have with your doctor.
An electrocardiogram (ECG) will be required before starting this medication and at various points during treatment. Consult with your doctor to understand the schedule and implications.
Your doctor may also request urine tests to monitor your condition. Adhere to the testing schedule as advised by your doctor.
You may require potassium supplements while taking this medication. Discuss your potassium levels and any necessary adjustments with your doctor.
If you are pregnant or planning to become pregnant, it is crucial to inform your doctor. You and your doctor will need to weigh the benefits and risks of continuing this medication during pregnancy to make an informed decision.
Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Be sure to discuss any concerns or questions you have with your doctor.
An electrocardiogram (ECG) will be required before starting this medication and at various points during treatment. Consult with your doctor to understand the schedule and implications.
Your doctor may also request urine tests to monitor your condition. Adhere to the testing schedule as advised by your doctor.
You may require potassium supplements while taking this medication. Discuss your potassium levels and any necessary adjustments with your doctor.
If you are pregnant or planning to become pregnant, it is crucial to inform your doctor. You and your doctor will need to weigh the benefits and risks of continuing this medication during pregnancy to make an informed decision.
Overdose Information
Overdose Symptoms:
- Signs of hypocortisolism (e.g., severe fatigue, nausea, vomiting, hypotension, dizziness)
- Electrolyte imbalances (e.g., hypokalemia)
- QTc prolongation
What to Do:
In case of suspected overdose, seek immediate medical attention or call a poison control center (1-800-222-1222). Management includes supportive care, monitoring of cortisol levels, electrolytes, and ECG, and potentially administering exogenous glucocorticoids if hypocortisolism is severe.
Drug Interactions
Major Interactions
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort) - may significantly decrease osilodrostat exposure, leading to loss of efficacy.
- Drugs that prolong the QT interval (e.g., Class IA and Class III antiarrhythmics, some antipsychotics, macrolide antibiotics, fluoroquinolones) - increased risk of QTc prolongation.
Moderate Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) - may increase osilodrostat exposure, increasing risk of adverse reactions (e.g., hypocortisolism).
- Drugs that cause bradycardia (e.g., beta-blockers, non-dihydropyridine calcium channel blockers, digoxin) - increased risk of bradycardia.
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess baseline QTc interval and identify risk factors for QTc prolongation.
Timing: Prior to initiation.
Serum Potassium
Rationale: To assess baseline potassium levels, as osilodrostat can cause hypokalemia.
Timing: Prior to initiation.
Blood Pressure
Rationale: To assess baseline blood pressure, as osilodrostat can affect blood pressure.
Timing: Prior to initiation.
Blood Glucose
Rationale: To assess baseline glucose levels, as osilodrostat can affect glucose metabolism.
Timing: Prior to initiation.
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function, especially given hepatic metabolism and potential for hepatic impairment dose adjustment.
Timing: Prior to initiation.
Routine Monitoring
24-hour Urinary Free Cortisol (UFC)
Frequency: Weekly or bi-weekly initially during titration, then monthly or as clinically indicated.
Target: Normalization of UFC levels.
Action Threshold: Adjust dose based on UFC levels and clinical response; reduce dose or temporarily interrupt if UFC is below normal range (hypocortisolism).
Serum Potassium
Frequency: Weekly or bi-weekly initially, then monthly or as clinically indicated.
Target: Normal range (3.5-5.0 mEq/L).
Action Threshold: Supplement potassium if hypokalemic; consider dose reduction if severe or persistent.
Blood Pressure
Frequency: Regularly, especially during dose titration.
Target: Individualized target.
Action Threshold: Manage hypertension or hypotension as appropriate; consider dose adjustment if related to osilodrostat.
Blood Glucose
Frequency: Regularly, especially in patients with diabetes or at risk.
Target: Individualized target.
Action Threshold: Adjust antidiabetic medications as needed.
Electrocardiogram (ECG)
Frequency: Periodically, especially with dose changes or if risk factors for QTc prolongation develop.
Target: QTc < 450 ms (men), < 470 ms (women).
Action Threshold: Interrupt or discontinue if QTc > 500 ms or increases by > 60 ms from baseline; correct electrolyte abnormalities.
Symptom Monitoring
- Symptoms of hypocortisolism/adrenal insufficiency (e.g., fatigue, nausea, vomiting, abdominal pain, dizziness, hypotension, weakness, weight loss)
- Symptoms of hypokalemia (e.g., muscle weakness, cramps, palpitations, fatigue)
- Symptoms of QTc prolongation (e.g., palpitations, dizziness, syncope)
- Symptoms of hypertension (e.g., headache, blurred vision)
- Symptoms of hyperglycemia (e.g., increased thirst, frequent urination, fatigue)
Special Patient Groups
Pregnancy
Osilodrostat may cause fetal harm when administered to a pregnant woman. Based on animal studies, it can cause adverse developmental effects. It is recommended to advise pregnant women of the potential risk to the fetus. Women of reproductive potential should 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.
Second Trimester:
Potential for fetal harm based on animal data.
Third Trimester:
Potential for fetal harm based on animal data.
Lactation
It is unknown if osilodrostat is 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:
High (potential for serious adverse reactions)
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Use is not recommended.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly and younger patients, but 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; close monitoring for hypocortisolism is crucial, especially during dose titration.
- Patients should be educated on the symptoms of adrenal insufficiency and instructed to seek immediate medical attention if they occur.
- Electrolyte imbalances, particularly hypokalemia, are common and require regular monitoring and supplementation.
- QTc prolongation and bradycardia are potential cardiac side effects; baseline and periodic ECGs are recommended, especially with dose changes or concomitant QTc-prolonging drugs.
- Blood pressure and glucose levels should be monitored regularly, as osilodrostat can affect both.
- Drug interactions, especially with CYP3A4 inducers/inhibitors, are significant and require dose adjustments or avoidance.
- Patients should carry a medical alert card indicating they are on Isturisa due to the risk of adrenal crisis if the drug is stopped suddenly or in times of stress.
Alternative Therapies
- Pasireotide (Signifor, Signifor LAR)
- Mifepristone (Korlym)
- Cabergoline (off-label)
- Ketoconazole (off-label)
- Adrenalectomy (bilateral)
- Transsphenoidal surgery (pituitary adenoma removal)
Cost & Coverage
Average Cost:
Highly variable, typically >$20,000 - $30,000+ per 60 tablets (10mg)
Insurance Coverage:
Specialty Tier (requires prior authorization, step therapy, and/or quantity limits)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it is a good idea to check with your pharmacist for more information. If you have any questions or concerns about your medication, do not hesitate to discuss them with 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 taken, the amount, and the time it happened.