Recorlev (levoketoconazole)
An approved treatment for Cushing Disease.
The same compound appears under different names depending on the context. Here is how to identify Levoketoconazole wherever you encounter it, plus the key facts at a glance.
- Generic name
- Levoketoconazole
- Brand name
- Recorlev
- Development code
- COR-003
- Drug class
- Cortisol synthesis inhibitor
- Manufacturer
- Xeris Biopharma
- How it's taken
- Taken by mouth twice daily, with or without food.
An oral cortisol synthesis inhibitor for adults with Cushing's syndrome. Levoketoconazole is the pure 2S,4R enantiomer of ketoconazole, designed to maintain the cortisol-lowering effect while improving the safety profile compared to racemic ketoconazole, which was used off-label for decades.
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Where Levoketoconazole fits
Cortisol synthesis inhibitor for Cushing's syndrome when surgery is not possible or has failed. Formalizes the long off-label use of ketoconazole as an FDA-approved treatment, though it carries boxed warnings for liver injury and QT prolongation like ketoconazole.
How Levoketoconazole works
Levoketoconazole blocks several enzymes in the adrenal glands that are needed to produce cortisol, including 11-beta-hydroxylase and 17,20-lyase. By inhibiting multiple steps in the cortisol production pathway, it reduces the amount of cortisol the adrenal glands release into the bloodstream. It is the purified active isomer of ketoconazole, which means it provides the cortisol-lowering benefit with approximately half the dose of racemic ketoconazole.
Mechanism: Cortisol synthesis inhibitor that blocks multiple steroidogenic enzymes including 11-beta-hydroxylase and 17,20-lyase
Side effects and safety
Carries boxed warnings for hepatotoxicity (liver damage) and QT prolongation (heart rhythm changes). Liver enzymes must be monitored before and during treatment. Common side effects include nausea, headache, hypokalemia, hypertension, and fatigue. Adrenal insufficiency can occur if cortisol drops too low. Serious allergic reactions can occur (anaphylaxis has been reported with ketoconazole), and it can lower testosterone in both men and women. The label says it must not be used by people with cirrhosis, acute or poorly controlled chronic liver disease, or certain heart rhythm problems, or together with certain medicines that affect heart rhythm or are processed by the CYP3A4 liver enzyme, so your doctor should review everything you take.
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Levoketoconazole
Taken by mouth twice daily, with or without food. Starting dose is 150 mg twice daily, increased gradually based on cortisol levels and tolerability. Maximum dose is 600 mg twice daily. Requires regular monitoring of liver enzymes, ECGs, potassium levels, and cortisol.
Availability and cost
Only available as the brand-name product.
Purified enantiomer of ketoconazole for a rare endocrine disorder. Requires extensive monitoring including liver function tests and ECGs during treatment.
Help paying for Recorlev
Pick your insurance to see which help fits. Drugmaker copay cards can't be used with Medicare, Medicaid or TRICARE; charity funds are the usual route there.
- Copay help
Eligible commercially insured patients may pay as little as $0. Eligibility requirements, restrictions and limits apply.
For: private insurance · source - Insurance and case manager help
A dedicated Patient Access Manager checks in regularly and helps with insurance; PANTHERx Rare Pharmacy, the only pharmacy that carries RECORLEV, delivers it to your home.
The official page does not say who qualifies. Ask the program. · source
Good to know: The pages say the team helps patients with and without insurance, and can share information if you have no health insurance. They do not describe a free-drug program or its eligibility.
- From a charity · HealthWell FoundationCushing's Disease or Cushing's Syndrome fundOpen
Pays for: Copays, premiums or other treatment costs.
- From a charity · NORD RareCareCushing's Syndrome Medical Assistance fundOpen
Pays for: Medical and medication costs.
The foundation says: “Accepting new applications and re-enrollments for current year” - From a charity · NORD RareCareCushing's Syndrome Premium Copay Assistance fundOpen
Pays for: Insurance premiums and copays.
The foundation says: “Accepting new applications and re-enrollments for current year” - From a charity · TotalAssist (formerly PAN Foundation)Cushing's Disease or Syndrome fundOpen
Pays for: Out-of-pocket costs for approved medications, up to $9,500 per year. Requires health insurance (any kind).
How Cushing disease treatments compare
Four FDA-approved medical therapies are available for Cushing's disease. Your endocrinologist will recommend a treatment based on the source of your excess cortisol, your blood sugar levels, surgical history, and how you respond to initial therapy. This chart summarizes the key practical differences between options.
4 FDA-approved cushing disease treatments are available: Isturisa (osilodrostat, approved 2020); Korlym (mifepristone, approved 2012); Recorlev (levoketoconazole, approved 2021); Signifor LAR (pasireotide, approved 2012). Isturisa is typically used as first-line medical therapy when surgery is not possible or has not been curative.
| Drug | How it works | How it’s given | How often | Where you get it | Typical use | FDA approved |
|---|---|---|---|---|---|---|
Isturisa osilodrostat | Cortisol synthesis inhibitor — blocks 11-beta-hydroxylase, the final enzyme step in cortisol production | Oral tablet | Twice daily | Home (self-administered) | First-line medical therapy when surgery is not possible or has not been curative | 2020 |
Korlym mifepristone | Glucocorticoid receptor blocker — blocks cortisol from binding to its receptor (does not lower cortisol levels) | Oral tablet | Once daily with a meal | Home (self-administered) | For Cushing's patients with type 2 diabetes or glucose intolerance when surgery is not an option or has failed | 2012 |
Recorlev levoketoconazole You are here | Cortisol synthesis inhibitor — blocks multiple steroidogenic enzymes including 11-beta-hydroxylase | Oral capsule | Twice daily with food | Home (self-administered) | For adults with Cushing's syndrome when surgery is not possible or has not been curative | 2021 |
Signifor LAR pasireotide | Pituitary-targeted somatostatin analog — suppresses ACTH secretion from the tumor, reducing the signal that drives cortisol production | Intramuscular injection (monthly) or subcutaneous injection (twice daily) | Monthly (LAR) or twice daily (subcutaneous) | LAR: doctor's office or infusion center; Subcutaneous: self-administered at home | For Cushing's disease (pituitary-dependent) when surgery is not an option or has failed; only drug that targets the tumor itself | 2012 |
This comparison is for FDA-approved medical therapies only and does not include surgical or radiation treatments, which are typically first-line for Cushing's disease. Always discuss treatment selection with your endocrinologist, who can factor in tumor size, cortisol severity, metabolic complications, and your individual response.
Clinical trial results
SONICS (open-label): 30% of patients achieved normalized urinary free cortisol after 6 months of maintenance without dose increase. LOGICS (randomized withdrawal): confirmed efficacy when patients randomized to placebo lost cortisol control significantly more often than those continuing levoketoconazole.
Development history
FDA approved December 2021 for endogenous hypercortisolemia in adults with Cushing's syndrome. Developed as a refined version of ketoconazole, which was widely used off-label for Cushing's. Ketoconazole itself was never FDA-approved for this indication.
Explore Cushing Disease trials
Other Cushing Disease treatments
Common questions about Levoketoconazole
▸What is Levoketoconazole (Recorlev)?
An oral cortisol synthesis inhibitor for adults with Cushing's syndrome. Levoketoconazole is the pure 2S,4R enantiomer of ketoconazole, designed to maintain the cortisol-lowering effect while improving the safety profile compared to racemic ketoconazole, which was used off-label for decades.
▸How does Levoketoconazole work?
Levoketoconazole blocks several enzymes in the adrenal glands that are needed to produce cortisol, including 11-beta-hydroxylase and 17,20-lyase. By inhibiting multiple steps in the cortisol production pathway, it reduces the amount of cortisol the adrenal glands release into the bloodstream. It is the purified active isomer of ketoconazole, which means it provides the cortisol-lowering benefit with approximately half the dose of racemic ketoconazole.
▸What are the side effects of Levoketoconazole?
Carries boxed warnings for hepatotoxicity (liver damage) and QT prolongation (heart rhythm changes). Liver enzymes must be monitored before and during treatment. Common side effects include nausea, headache, hypokalemia, hypertension, and fatigue. Adrenal insufficiency can occur if cortisol drops too low. Serious allergic reactions can occur (anaphylaxis has been reported with ketoconazole), and it can lower testosterone in both men and women. The label says it must not be used by people with cirrhosis, acute or poorly controlled chronic liver disease, or certain heart rhythm problems, or together with certain medicines that affect heart rhythm or are processed by the CYP3A4 liver enzyme, so your doctor should review everything you take.
▸How is Levoketoconazole taken?
Taken by mouth twice daily, with or without food. Starting dose is 150 mg twice daily, increased gradually based on cortisol levels and tolerability. Maximum dose is 600 mg twice daily. Requires regular monitoring of liver enzymes, ECGs, potassium levels, and cortisol.
▸Is Levoketoconazole FDA approved?
Yes, Levoketoconazole (Recorlev) is FDA approved (2021) for the treatment of Cushing Disease.
▸How does levoketoconazole differ from regular ketoconazole?
Levoketoconazole is the purified 2S,4R enantiomer of ketoconazole, meaning it is a single mirror-image form of the molecule. This provides more potent cortisol-lowering activity with a potentially improved safety profile compared to racemic ketoconazole, which contains both mirror forms.
▸What enzymes does levoketoconazole block?
Levoketoconazole blocks multiple steroidogenic enzymes including 11-beta-hydroxylase and 17,20-lyase, providing broad inhibition of cortisol synthesis. This multi-enzyme approach helps ensure effective cortisol reduction.
▸What liver monitoring is needed?
Liver function tests are required before starting and regularly during treatment, as levoketoconazole can cause liver enzyme elevations. Significant liver toxicity is a known risk with ketoconazole-class drugs.
▸How is Recorlev taken?
Recorlev is taken orally, with the dose titrated based on cortisol levels. Treatment starts at a low dose and is gradually increased to achieve normal cortisol without over-suppression.
▸When was levoketoconazole approved?
Levoketoconazole (Recorlev) was approved by the FDA in December 2021 to treat high cortisol in adults with Cushing's syndrome when surgery is not an option or has not cured it. It is marketed by Xeris Biopharma.
▸How does levoketoconazole compare to osilodrostat?
Both reduce cortisol production but target different enzymes. Osilodrostat specifically blocks 11-beta-hydroxylase (the final step), while levoketoconazole blocks multiple enzymes in the steroid synthesis pathway. The choice depends on individual patient factors and tolerability.