Crenessity (crinecerfont)

When used concomitantly with a moderate CYP3A4 inducer in pediatric patients, the recommended dosage of crinecerfont is as follows:

10 to <20 kg: morning dose is 25 mg and evening dose is 50 mg.

20 to <55 kg: morning dose is 50 mg and evening dose is 100 mg.

>=55 kg: morning dose is 100 mg and evening dose is 200 mg.

When used concomitantly with a moderate CYP3A4 inducer, increase the crinecerfont dosage to a morning dose of 100 mg and an evening dose of 200 mg.

When used concomitantly with a strong CYP3A4 inducer in pediatric patients, the recommended dosage of crinecerfont is as follows:

10 to <20 kg: 50 mg twice daily.

20 to <55 kg: 100 mg twice daily.

>=55 kg: 200 mg twice daily.

When used concomitantly with a strong CYP3A4 inducer, increase the crinecerfont dosage to 200 mg twice daily.

Administer crinecerfont orally, twice daily with a meal in the morning and evening. The drug is commercially available as capsules and an oral solution.

No dosing information is available for this tab.

Crinecerfont is metabolized primarily by cytochrome P-450 (CYP) 3A4 and to a lesser extent by CYP2B6.

Crinecerfont is unlikely to induce CYP3A, CYP1A2, CYP2C8, CYP2C9, CYP2B6 or inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 at clinically relevant doses.

Crinecerfont is a weak CYP3A inhibitor. Crinecerfont is not an inhibitor of P-glycoprotein (P-gp), breast cancer resistant protein (BCRP), bile salt export pump (BSEP), organic anion transporting polypeptide (OATP)1B1, or OATP1B3, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT) 2, multidrug and toxin extrusion transporter (MATE)1, or MATE2-K. Crinecerfont is not a substrate for transporters P-gp, BCRP, BSEP, OATP1B1, or OATP1B3.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Crinecerfont/Moderate Cyp3a4 Inducers

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of crinecerfont.(1)

CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may reduce the clinical effectiveness of crinecerfont.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The US manufacturer of crinecerfont states that concurrent use of moderate CYP3A4 inducers requires a dose adjustment of crinecerfont. Increase the evening dose of crinecerfont by 2-fold. Do not increase the morning dose. In adults, increase the dosage of crinecerfont to 100 mg in the morning and 200 mg in the evening. In pediatric patients 4 years and older weighing: - 10 kg to <20 kg: increase the crinecerfont dosage to 25 mg in the morning and 50 mg in the evening, - 20 kg to <55 kg: increase the crinecerfont dosage to 50 mg in the morning and 100 mg in the evening, - >=55 kg: increase the crinecerfont dosage to 100 mg in the morning and 200 mg in the evening.(1)

DISCUSSION: In a study, concomitant use of rifampin (strong CYP3A4 inducer) decreased crinecerfont maximum concentration (Cmax) by 23% and area-under-curve (AUC) by 62%.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3)

Crinecerfont/Strong Cyp3a4 Inducers

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Strong inducers of CYP3A4 may induce the metabolism of crinecerfont.(1)

CLINICAL EFFECTS: Concurrent or recent use of strong CYP3A4 inducers may reduce the clinical effectiveness of crinecerfont.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The US manufacturer of crinecerfont states that concurrent use of strong CYP3A4 inducers requires a dose adjustment of crinecerfont. Increase the morning and evening doses of crinecerfont by 2-fold. In adults, increase the dosage of crinecerfont to 200 mg twice daily. In pediatric patients 4 years and older weighing: - 10 kg to <20 kg: increase the crinecerfont dosage to 50 mg twice daily, - 20 kg to <55 kg: increase the crinecerfont dosage to 100 mg twice daily, - >=55 kg: increase the crinecerfont dosage to 200 mg twice daily.(1)

DISCUSSION: In a study, concomitant use of rifampin (strong CYP3A4 inducer) decreased crinecerfont maximum concentration (Cmax) by 23% and area-under-curve (AUC) by 62%.(1) Strong CYP3A4 inducers linked to this monograph are: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's Wort.(2,3)

*Hypersensitivity to crinecerfont or any excipients in the formulation.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

The most common adverse reactions (>=4% for crinecerfont and greater than placebo) reported in adults receiving crinecerfont in clinical trials were fatigue, headache, dizziness, arthralgia, back pain, decreased appetite, and myalgia. The most common adverse reactions (>=4% for crinecerfont and greater than placebo) reported in pediatrics were headache, abdominal pain, fatigue, nasal congestion, and epistaxis.

Rare or Very Rare

• Angioedema
• Suicidal ideation

More Frequent

• Acute abdominal pain
• Anorexia
• Arthralgia
• Back pain
• Dizziness
• Epistaxis
• Fatigue
• Headache disorder
• Myalgia
• Nasal congestion

Less Frequent

• Neutropenic disorder

Rare or Very Rare

• Dyspepsia
• Indifference
• Nausea
• Nervousness
• Skin rash
• Vomiting

No enhanced messaging available.

Safety and effectiveness of crinecerfont as adjunctive treatment to glucocorticoid replacement to control androgens have been established in pediatric patients 4 years of age and older with classic CAH. Use of crinecerfont for CAH is supported by evidence from an adequate and well-controlled study of 103 pediatric patients, evidence from an adequate and well-controlled study in adults with CAH, and pharmacokinetic data from adults and pediatric patients.

Safety and effectiveness of crinecerfont in pediatric patients less than 4 years of age have not been established.

Available data from reports of pregnancy in clinical trials with crinecerfont are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.

No developmental toxicity was observed in rats at 4-fold higher than human exposure at the maximum recommended human dose (MRHD) based on AUC. Crinecerfont was associated with a low incidence of poly-malformations (craniofacial defects) in rabbits at 2-fold higher than human exposure at the MRHD. In a pre- and postnatal developmental toxicity study, no developmental toxicity was observed in rats at 4-fold higher than human exposure at the MRHD.

If crinecerfont is administered during pregnancy or if a patient becomes pregnant while receiving the drug, the exposure should be reported to 1-855-CRNSITY (1-855-276-7489).

There are no data on the presence of crinecerfont in human milk, or the effects of the drug on the breastfed infant or on milk production. Crinecerfont is present in animal milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Infants exposed to crinecerfont through breast milk should be monitored for signs of adrenal insufficiency such as weakness, decreased feeding, and weight loss.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for crinecerfont and any potential adverse effects on the breastfed child from the drug or underlying maternal condition.

The manufacturer makes no specific dosage recommendation for geriatric patients.

The principal clinical trial of crinecerfont in adults with classic CAH did not enroll patients >=65 years of age to determine whether they respond differently from younger patients.