Prescribing guide
Isturisa (osilodrostat)ECG and electrolyte checks, cortisol-guided titration, hypocortisolism management and prior authorization criteria for Cushing syndromeFor prescribers and their offices treating cushing syndrome, including Cushing disease: what the pharmacy needs before it ships, what the prior authorization wants documented, the titration and the monitoring the label requires.
Dispensing gate
No REMS; baseline ECG, correction of hypokalemia and hypomagnesemia, a CYP3A4 and QT medication review, prior authorization, and a Patient Prescription Form sent to Anovo.
Example PA threshold
Cigna example: age 18 or older, documented endogenous Cushing syndrome, surgery not an option or not curative or awaiting surgery or radiotherapy response, endocrinologist, preferred product step unless already on Isturisa.
Monitoring
ECG at baseline and within 1 week, then as indicated; two 24-hour UFC collections every 1 to 2 weeks during titration, then cortisol at least every 1 to 2 months; potassium and magnesium periodically; hypocortisolism signs at any time.
Support line
Recordati Rare Diseases R.A.R.E. Patient Support 1-888-855-7273 (1-888-855-RARE), prescriptions filled by Anovo (fax 1-855-917-3510, NCPDP 4445640), $20 co-pay for qualified commercially insured patients.
Give your patient their plan
A one-page handout for starting Isturisa, in plain language: what the first fill waits on, the first dates, who will call and the symptoms to report, with blank lines for the start date and your office's number. The link opens the patient's full first 90 days page, where their dates become calendar entries.
trialfriend.com/p/isturisaBefore the first fill: REMS, labs and enrollment
The steps that the pharmacy, the REMS or the drugmaker's program will wait on, in the order they usually need to happen. A first fill of a specialty drug most often stalls on one of these rather than on the plan.
| Step | What it requires | Source |
|---|---|---|
| No REMS | The label and the FDA approval letters set no REMS and no restricted dispensing program. The label has no boxed warning and no contraindications. | FDA label |
| Baseline ECG and electrolytes | Obtain a baseline ECG and correct hypokalemia and hypomagnesemia before starting (section 2.1). Recordati's prescriber pages say to test potassium and magnesium before the first dose. | FDA label |
| Medication reconciliation | Strong CYP3A4 inhibitors halve the dose; strong CYP3A4 and CYP2B6 inducers may require a higher dose. Review QT-prolonging drugs and narrow therapeutic index CYP1A2 or CYP2C19 substrates such as theophylline and tizanidine. | FDA label |
| Prescription to Anovo | All Isturisa prescriptions are filled through Anovo. Fax the completed Patient Prescription Form to Anovo Specialty Rx at 1-855-917-3510, NCPDP 4445640, or submit electronically choosing Anovo#5. | Isturisa HCP support |
| Form details | The form (revised October 26, 2026) lists 1mg and 5mg tablets, a 1-month or 3-month dispense and space for titration instructions, and notes prior authorization may be needed for each strength. Prescriber signature only, no stamps; refax or call 1-888-855-7273 if no confirmation within 24 hours. | Prescription form |
| Patient authorization | Page 2 is a patient authorization for R.A.R.E., covering insurance investigation, commercial copay help and assessment of eligibility for free medication supply. The form asks that both pages be submitted. | Prescription form |
| Benefits and prior authorization | R.A.R.E. investigates benefits, then faxes the office the plan's prior authorization form or provides a CoverMyMeds key. Once benefits are established, a pharmacist calls the patient to arrange overnight delivery. | Quick Start Guide |
Prior authorization criteria and what to document
One public policy as the example: Cigna, May 1, 2026. Approval approved for 1 year. The policy lists no separate renewal criteria. This version took effect May 1, 2026, after an April 9, 2026 review with no criteria changes. It cites the November 2025 label, which is the current one. Its overview still says pituitary surgery, while the label says surgery. Other plans set their own criteria and their own approval lengths. It is here as an example of what a plan asks for, not as a rule.
| Element | What the policy asks | In the chart | Source |
|---|---|---|---|
| Age | 18 or older | Date of birth on the request | Cigna policy |
| Diagnosis | Confirmed endogenous Cushing syndrome; the policy notes Cushing disease is included | Chart note, laboratory or medical test results, marked documentation required | Cigna policy |
| Surgical status | Per the prescriber, not a surgical candidate or surgery not curative; or awaiting surgery; or awaiting therapeutic response after radiotherapy | Operative or consult note, or radiotherapy record | Cigna policy |
| Prescriber | Prescribed by or in consultation with an endocrinologist or a physician who specializes in endogenous Cushing syndrome | Specialty on the request, or the consult note | Cigna policy |
| Preferred product, Cushing disease | Tried or currently taking Signifor or Signifor LAR, or already started on Isturisa (employer and individual plans) | Fill history or chart note | Cigna policy |
| Preferred product, other endogenous Cushing syndrome | Tried with inadequate efficacy or significant intolerance, or currently taking, oral ketoconazole, Metopirone or Recorlev, or already started on Isturisa | Fill history and a note on response or intolerance; samples do not satisfy criteria | Cigna policy |
| Approval and quantity | Approval for 1 year. Cigna's separate quantity policy caps retail fills at 240 1mg tablets and 60 5mg tablets, with exceptions for 6mg to 9mg twice daily and for 15mg or 25mg twice daily | Dose and tablet count on the prescription | Cigna quantity policy |
Isturisa dosing and titration
| When | Label | Source |
|---|---|---|
| Start | 2mg orally twice daily, with or without food. | FDA label |
| Titration | Increase by 1mg to 2mg twice daily no more frequently than every 2 weeks, based on the rate of cortisol change, tolerability and signs and symptoms. | FDA label |
| Above 10mg twice daily | If 10mg twice daily is tolerated and 24-hour UFC remains above ULN, titrate by 5mg twice daily every 2 weeks. Maximum 30mg twice daily. | FDA label |
| Maintenance | Individualized from cortisol levels and signs and symptoms; maintenance doses varied between 2mg and 7mg twice daily in the trials. | FDA label |
| Hepatic impairment | Child-Pugh B, start 1mg twice daily; Child-Pugh C, start 1mg once daily in the evening; no change for Child-Pugh A. Monitor adrenal function more often during titration. | FDA label |
| Renal impairment | No dose adjustment. Interpret UFC with caution in moderate to severe renal impairment because UFC excretion is reduced. | FDA label |
| Interruptions and missed doses | After an interruption, re-initiate at a lower dose once cortisol is in range and symptoms resolve. For a missed dose, take the next dose at the scheduled time. | FDA label |
| Supply | 1mg and 5mg tablets, 60 per carton as 6 blister packs of 10 (NDC 55292-330-60 and 55292-331-60). At 2mg twice daily, one 1mg carton covers 15 days. | FDA label |
| 10mg tablet | Drugs@FDA lists the 10mg strength as discontinued, with a Federal Register determination that it was not withdrawn for safety or effectiveness reasons. | Drugs@FDA record |
Monitoring the Isturisa label requires
| When | What | What the label says to do with it | Source |
|---|---|---|---|
| Baseline | ECG; potassium and magnesium | Correct hypokalemia and hypomagnesemia before starting | FDA label |
| Within 1 week | Repeat ECG | Then as clinically indicated; more frequent ECGs with QT risk factors such as congenital long QT, heart failure, bradyarrhythmias or QT-prolonging drugs | FDA label |
| QTc above 480ms | QTc interval | Consider temporary discontinuation; correct electrolytes. Mean QTcF increase estimated at 5.3ms at 30mg twice daily | FDA label |
| Every 1 to 2 weeks during titration | At least two 24-hour UFC collections | Until adequate clinical response is maintained; then cortisol at least every 1 to 2 months or as indicated | FDA label |
| Any time | Hypocortisolism: nausea, vomiting, fatigue, abdominal pain, anorexia, dizziness, hypotension, electrolyte changes, hypoglycemia | Reported in 31% up to week 12 and 18% from weeks 12 to 26 in Study 1; evaluate for precipitants such as infection or physical stress | FDA label |
| Periodically | Potassium, blood pressure, edema | Hypokalemia 17% and hypertension 14% in Study 1; treat with potassium, add a mineralocorticoid antagonist if it persists; dose reduction or discontinuation may be needed | FDA label |
| Females | Hirsutism, hypertrichosis, acne | Testosterone rose above normal in females and reversed on interruption; hirsutism 12% and acne 11% in a subset | FDA label |
| Postmarketing | Neutropenia associated with fever and infection | Listed in section 6.2; in Study 2, 6% had an ANC below normal and 2% grade 3 | FDA label |
Isturisa drug interactions and contraindications
| Label category | Agents and what the label says | Source |
|---|---|---|
| Strong CYP3A4 inhibitors (itraconazole, clarithromycin) | Reduce the Isturisa dose by half. | FDA label |
| Strong CYP3A4 and CYP2B6 inducers (carbamazepine, rifampin, phenobarbital) | Monitor cortisol and symptoms; an increase may be needed. When the inducer is stopped, a dose reduction may be needed. | FDA label |
| Narrow therapeutic index CYP1A2 and CYP2C19 substrates | Use with caution with theophylline, tizanidine and S-mephenytoin. A 50mg osilodrostat dose raised caffeine exposure 2.5-fold and omeprazole 1.9-fold. | FDA label |
| QT-prolonging medicines | Listed as a risk factor for QT prolongation; use caution and consider more frequent ECG monitoring. | FDA label |
| Oral contraceptives | 30mg twice daily for 12 days had no significant effect on estradiol 0.03mg and levonorgestrel 0.15mg exposure. | FDA label |
| Lactation | Breastfeeding not recommended during treatment and for at least 1 week after the final dose. | FDA label |
| Earlier labeling | The April 2025 label lists the same 1mg and 5mg strengths, but in cartons of 3 blister packs of 20 under NDCs 55292-320-60 and 55292-321-60. | April 2025 label |
Why a first fill stalls, and the fix
- The plan wants another cortisol medicine tried firstCigna's employer plans may ask for a trial of Signifor for Cushing disease, or of ketoconazole, Metopirone or Recorlev for other causes. A person who has already started Isturisa also meets this rule. The endocrinologist's office decides how to answer and can document a past trial or a reason.
- Prior authorization pending or deniedCigna asks for age 18 or older, a documented diagnosis of endogenous Cushing syndrome and an endocrinologist. It also wants surgery ruled out or not curative, or the patient awaiting surgery or a radiation response. The policy marks the diagnosis as documentation required, so the office sends chart notes or lab results.
- The pharmacy will not fill the full number of tabletsCigna's quantity policy caps 1mg tablets at 240 and 5mg tablets at 60 per retail fill. It approves more tablets for certain twice-a-day doses listed in the policy. The office can ask for the exception that matches the prescribed dose.
- The prescription went to the wrong pharmacyRecordati says all Isturisa prescriptions are filled through Anovo, its specialty pharmacy. The office sends the Patient Prescription Form to Anovo by fax or through its electronic records system. Questions about the form or the shipment go to R.A.R.E. at 1-888-855-7273.
- A copay you cannot payWith commercial insurance, Recordati offers a $20 co-pay for qualified patients, and eligibility rules apply. Recordati's R.A.R.E. team also helps people identify other financial assistance options. Our help paying page lists charity funds that may cover Cushing syndrome costs.
R.A.R.E. Patient Support Program (Recordati Rare Diseases, with Anovo)
- A $20 co-pay for qualified patients with commercial insurance, with eligibility requirements, restrictions and limitations
- Help with prior authorization and appeals, and a check of insurance benefits
- Help finding other financial assistance options
- Nurse Educators who check in and answer questions about Isturisa after it starts
- An optional Patient Liaison for disease education and resources, at no cost
- Overnight delivery from Anovo, arranged by a pharmacist once benefits are set, with pharmacy support 24/7 Quick Start Guide
- A patient assistance program for people without insurance who meet financial requirements Recordati support programs
Questions prescribers' offices ask about Isturisa
What is the Isturisa titration schedule?
Start 2mg twice daily with or without food, then titrate by 1mg to 2mg twice daily no more frequently than every 2 weeks, per the November 2025 label (section 2.2). If 10mg twice daily is tolerated and 24-hour UFC stays above ULN, titrate by 5mg twice daily every 2 weeks. Maximum 30mg twice daily; trial maintenance doses varied between 2mg and 7mg twice daily.
What ECG and electrolyte monitoring does Isturisa require?
A baseline ECG, correction of hypokalemia and hypomagnesemia before the first dose, and a repeat ECG within 1 week of initiation, per the November 2025 label (sections 2.1 and 5.2). Repeat ECGs as clinically indicated, monitor potassium and magnesium periodically, and consider temporary discontinuation if QTc rises above 480ms.
How should hypocortisolism be managed on Isturisa?
Decrease or temporarily discontinue Isturisa if UFC falls below target, cortisol drops rapidly or the patient reports hypocortisolism symptoms, per the November 2025 label (sections 2.3 and 5.1). Stop it and give glucocorticoid replacement if serum or plasma cortisol is below target with adrenal insufficiency symptoms. Suppression may persist beyond the 4-hour half-life; re-initiate at a lower dose once cortisol is in range and symptoms resolve.
Does Isturisa have a REMS?
No. The November 2025 label has no REMS, no boxed warning and no contraindications, and none of the 4 FDA approval letters reviewed, from 2020 through 2025, sets one. Dispensing is limited in practice to Anovo, Recordati's specialty pharmacy partner.
What do insurers ask for to approve Isturisa?
The Cigna policy shown here, effective May 1, 2026, asks for age 18 or older, a documented diagnosis of endogenous Cushing syndrome, surgery not an option or not curative (or awaiting surgery or a radiotherapy response) and an endocrinologist, with 1-year approval. Its preferred product step asks for Signifor in Cushing disease, or ketoconazole, Metopirone or Recorlev in other endogenous Cushing syndrome, unless the patient is already on Isturisa.
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Sources
- ISTURISA- osilodrostat tablet, coated: prescribing information and Patient Information, revised 11/2025, Recordati Rare Diseases, Inc., via DailyMed, 2025-11-18.
- ISTURISA (osilodrostat) tablets prescribing information and Patient Information, revised 04/2025, FDA, Drugs@FDA, 2025-04-15.
- ISTURISA (osilodrostat) Patient Support, R.A.R.E. Program, Recordati Rare Diseases Inc., 2026-11-10.
- Starting ISTURISA (osilodrostat) for Cushing's, Recordati Rare Diseases Inc., 2026-11-10.
- ISTURISA (osilodrostat), Resources & Support, Recordati Rare Diseases Inc., 2026-11-10.
- ISTURISA (osilodrostat) Patient Prescription Form, ISTURISA.RX.01, revised October 26, 2026, Recordati Rare Diseases Inc. and AnovoRx, 2026-10-26.
- ISTURISA Quick Start Guide, Endogenous Hypercortisolemia in Cushing's Syndrome, PP-IST-US-0674, Recordati Rare Diseases Inc., 2026-11-10.
- Our Focus, Patient Support Programs, Recordati Rare Diseases Inc., 2026-11-10.
- Drug Coverage Policy IP0044, Isturisa (Cushing's, Isturisa), Cigna, 2026-05-01.
- Cushing's Disease, Isturisa Drug Quantity Management Policy, Per Rx, Cigna, 2026-05-13.
- Drugs@FDA record for NDA 212801, Isturisa, via openFDA, FDA, 2026-11-10.
- NDA 212801/S-007 supplement approval letter, corrected, removal of the wallet and sleeve for the blister pack of 20, FDA, 2025-11-04.
- NDA 212801/S-004 supplement approval letter, final results of Clinical Trial C2302 and febrile neutropenia, FDA, 2025-07-03.
- NDA 212801/S-003 supplement approval letter, indication broadened to Cushing's syndrome, FDA, 2025-04-15.
- NDA 212801 approval letter, Isturisa (osilodrostat) tablets, FDA, 2020-03-06.
A reference drawn from the November 18, 2025 label, the drugmaker's published program and one public insurer policy shown as an example, checked on November 10, 2026. Labels and policies change; the label on DailyMed and the plan's current policy govern. Trial Friend is not a medical provider. It reports what these documents say and does not judge whether a drug is safe or right for any patient; that is the prescriber's decision. Not a substitute for the prescribing information.