Crinecerfont
CRENESSITY
What it isCRF1 antagonist reducing pituitary ACTH drive; classic congenital adrenal hyperplasia.
Why this oneIt lowers adrenal androgen drive so glucocorticoids can move toward replacement rather than chronic supraphysiologic suppression.
What limits itReducing glucocorticoids too quickly can trigger adrenal insufficiency; CYP3A4 interactions require review.
FDA-approved for
- congenital adrenal hyperplasia (2024)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Congenital adrenal hyperplasia (adjunct to glucocorticoid) | Adults | 100 mg BID with a meal (AM & PM) | 100 mg BID | 100 mg BID |
| Congenital adrenal hyperplasia (adjunct to glucocorticoid) | Peds ≥4 y, weight-based | 10–<20 kg: 25 mg BID; 20–<55 kg: 50 mg BID; ≥55 kg: 100 mg BID | 25–100 mg BID by weight | 100 mg BID |
Renal Undefined
Hepatic Undefined
With strong CYP3A4 inducers, increase dose: adults 200 mg BID; pediatrics per weight table
Instructions
- Take with a meal in the morning and evening
- Continue glucocorticoid replacement therapy; do not reduce glucocorticoid below the dose required for cortisol replacement
- Use glucocorticoid stress doses for increased cortisol need (acute illness, trauma, surgery)
- Androstenedione may be assessed from 4 weeks to guide glucocorticoid reduction
Cautions
- Hypersensitivity reactions (throat tightness, angioedema, generalized rash) — discontinue if clinically significant
- Risk of acute adrenal insufficiency or adrenal crisis with inadequate concomitant glucocorticoid therapy
Adverse reactions
- Adults: fatigue, headache, dizziness, arthralgia, back pain, decreased appetite, myalgia
- Pediatrics: headache, abdominal pain, fatigue, nasal congestion, epistaxis
Pregnancy Data insufficient; low incidence of craniofacial malformations in rabbits at 2× exposure
Lactation No human milk data; present in animal milk; monitor infant for adrenal insufficiency
NO BOXED WARNINGS
Principal riskAdrenal insufficiency if glucocorticoid is cut too fast
Cost, est. cash$7,000–$12,000/month
Generic entry2038 est.
Classes and tags
Clinical profile
Legacy pregnancy categoryNot assigned — PLLR-era drug
Defining liabilityGenerally tolerated at therapeutic doses; clinically important risks are agent-specific and increase with interactions or organ impairment.
Mechanism of action: Crinecerfont ballicule
