Pregnancy Exclusion Before Starting Isturisa or Recorlev
Yes, pregnancy must be excluded before initiating either Isturisa (osilodrostat) or Recorlev (levoketoconazole) in women of childbearing potential, and both drugs should be discontinued immediately if pregnancy occurs.
Critical Safety Information
Recorlev (Levoketoconazole)
Recorlev explicitly requires pregnancy exclusion and contraception. The FDA label states: "are pregnant or plan to become pregnant. RECORLEV may harm your unborn baby. Tell your healthcare provider right away if you become pregnant during treatment with RECORLEV or think you might be pregnant" 1. This is a clear contraindication requiring:
- Negative pregnancy test before initiation
- Reliable contraception during treatment
- Immediate discontinuation if pregnancy occurs
- Notification to healthcare provider if pregnancy is suspected
The drug can pass into breast milk, requiring cessation of breastfeeding during treatment and for 1 day after the final dose 1.
Isturisa (Osilodrostat)
While the FDA label for Isturisa does not explicitly state pregnancy as a contraindication in the "CONTRAINDICATIONS" section (which lists "None") 2, this does not mean the drug is safe in pregnancy. The absence of a formal contraindication reflects insufficient data rather than proven safety.
Critical emerging evidence demonstrates fetal risk:
A 2025 case report documented osilodrostat exposure during early pregnancy (first 16 weeks) in a patient with Cushing disease 3. The pregnancy resulted in preterm rupture of membranes at 26 weeks, emergency cesarean delivery, and while the newborn developed normally without adrenal insufficiency, this single case cannot establish safety.
The patient unknowingly became pregnant while on osilodrostat due to irregular menstruation—a common feature in Cushing disease that makes pregnancy detection difficult 3.
Clinical Practice Algorithm
For All Women of Childbearing Potential:
Before initiating either medication:
- Obtain negative pregnancy test (serum β-hCG preferred)
- Counsel on teratogenic potential and unknown fetal risks
- Establish reliable contraception (barrier methods plus hormonal contraception recommended)
- Document counseling in medical record
During treatment:
- Monthly pregnancy testing is prudent given irregular menstruation in Cushing disease patients
- Reinforce contraception compliance at each visit
- Educate patients to report missed periods immediately
If pregnancy occurs:
- Discontinue medication immediately
- Transition to alternative management strategies (pasireotide with careful glucose monitoring, or metyrapone if tolerated) 3
- Establish multidisciplinary care with maternal-fetal medicine
- Monitor for tumor progression and maternal complications
Important Caveats
The irregular menstruation characteristic of Cushing disease creates a dangerous window where patients may not recognize pregnancy early. This was demonstrated in the case where pregnancy was detected at 16 weeks 3. This underscores why:
- Routine pregnancy testing cannot be skipped
- Patient education about early pregnancy symptoms is critical
- Home pregnancy tests should be provided for patients to use with any missed period
Pasireotide as an alternative during pregnancy carries its own significant risks, particularly severe hyperglycemia due to insulin and incretin suppression, requiring intensive glucose monitoring 3. This is not a benign alternative.
The lack of explicit pregnancy contraindication in Isturisa's FDA label should not be misinterpreted as safety—it reflects the absence of adequate human pregnancy data. The 2021 guideline on osilodrostat management does not address pregnancy, further highlighting the knowledge gap 4.
Given the known teratogenic potential of related medications in Cushing disease treatment and the documented case of adverse pregnancy outcomes with osilodrostat exposure, pregnancy exclusion before initiating either medication is mandatory for patient safety and medicolegal protection.