Crinecerfont
FDA Drug Information • Also known as: Crenessity
- Brand Names
- Crenessity
- Drug Class
- Corticotropin-releasing Factor Type 1 Receptor Antagonist [EPC]
- Route
- ORAL
- Dosage Form
- CAPSULE
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION CRENESSITY contains crinecerfont, a selective corticotropin-releasing factor type 1 receptor antagonist, present as crinecerfont free base, with the chemical name, 2-thiazolamine, 4-(2-chloro-4-methoxy-5-methylphenyl)- N -[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl- N -2-propyn-1-yl. Crinecerfont free base is the S-enantiomer with an enantiomeric excess of at least 99.7%. Its molecular formula is C 27 H 28 ClFN 2 OS, and its molecular weight is 483.04 g/mol with the following structure: CRENESSITY Capsules CRENESSITY capsules are intended for oral administration only. Each capsule contains 25 mg, 50 mg, or 100 mg of crinecerfont free base. Inactive ingredients include lauroyl polyoxyl-32 glycerides, medium chain triglycerides, propylene glycol dicaprylate/dicaprate, and Vitamin E polyethylene glycol succinate. The capsule shell contains gelatin, glycerin, red iron oxide, Sorbitol glycerin blend, titanium dioxide, and yellow iron oxide. CRENESSITY Oral Solution The oral solution formulation contains 50 mg/mL of crinecerfont free base. Inactive ingredients include butylated hydroxytoluene, medium-chain triglycerides, oleoyl polyoxyl glycerides, orange flavor, and saccharin. Its molecular formula is C27H28ClFN2OS, and its molecular weight is 483.04 g/mol with the following structure
What Is Crinecerfont Used For?
1 INDICATIONS AND USAGE CRENESSITY is indicated as adjunctive treatment to glucocorticoid replacement to control androgens in adults and pediatric patients 4 years of age and older with classic congenital adrenal hyperplasia (CAH) . CRENESSITY is a corticotropin-releasing factor type 1 receptor antagonist indicated as adjunctive treatment to glucocorticoid replacement to control androgens in adults and pediatric patients 4 years of age and older with classic congenital adrenal hyperplasia (CAH).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Continue glucocorticoid replacement therapy for adrenal insufficiency associated with CAH. ( 2.1 ) Adults : 100 mg orally, twice daily with a meal in the morning and evening. ( 2.2 ) Pediatric Patients (4 years of age and older ) : Weight-based dosage orally, twice daily with a meal in the morning and evening. ( 2.2 ) See Full Prescribing Information for complete dosage and administration information. 2.1 Important Administration Information Patients receiving CRENESSITY should continue glucocorticoid replacement therapy for the adrenal insufficiency associated with congenital adrenal hyperplasia (see Warning and Precautions ( 5.2 ) . Androstenedione levels can be assessed beginning four weeks after CRENESSITY initiation to inform reduction in glucocorticoid dosage as clinically indicated. Do not reduce the glucocorticoid dosage below that required for replacement therapy. 2.2 Recommended Dosage and Administration Recommended Dosage for Adults The recommended CRENESSITY dosage for adults is 100 mg orally, twice daily with a meal in the morning and evening [see Clinical Pharmacology ( 12.3 )] . Recommended Dosage for Pediatric Patients 4 Years of Age and Older The recommended CRENESSITY dosage for pediatric patients 4 years of age and older is weight-based and administered orally, twice daily with a meal in the morning and evening (see Table 1 ) [see Clinical Pharmacology ( 12.3 )] . Table 1 : Recommended CRENESSITY Weight-Based Dosage for Pediatric Patients 4 Years of Age and Older Weight Dosage Regimen with a Meal 10 kg to less than 20 kg 25 mg orally twice daily 20 kg to less than 55 kg 50 mg orally twice daily Greater than or equal to 55 kg 100 mg orally twice daily 2.3 Dosage Modifications for Concomitant Use with Strong CYP3A4 Inducers Adults In adults, increase the CRENESSITY dosage to 200 mg orally, twice daily with a meal in the morning and evening when used concomitantly with strong CYP3A4 inducers [see Drug Interactions ( 7.1 )] . Pediatric Patients 4 Years of Age and Older In pediatric patients, increase the CRENESSITY dosage with a meal in the morning and evening when used concomitantly with strong CYP3A4 inducers as shown in Table 2 [see Drug Interactions ( 7.1 ) ]. Table 2 : Dosage Increase of CRENESSITY for Use with Strong CYP3A4 Inducers in Pediatric Patients 4 Years of Age and Older Weight Dosage Regimen with a Meal 10 kg to less than 20 kg 50 mg orally twice daily 20 kg to less than 55 kg 100 mg orally twice daily Greater than or equal to <55 kg 200 mg orally twice daily 2.4 Dosage Modifications for Concomitant Use with Moderate CYP3A4 Inducers Adults In adults, increase the CRENESSITY dosage to 200 mg orally with the evening meal when used concomitantly with moderate CYP3A4 inducers. The CRENESSITY dosage of 100 mg with the morning meal remains unchanged [see Drug Interactions ( 7.1 )] . Pediatric Patients 4 Years of Age and Older In pediatric patients, increase the CRENESSITY dosage with the...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Risk of Acute Adrenal Insufficiency or Adrenal Crisis with Inadequate Concomitant Glucocorticoid Therapy [see Warnings and Precautions ( 5.2 )] Adults: Most common adverse reactions (at least 4% for CRENESSITY and greater than placebo) are fatigue, headache, dizziness, arthralgia, back pain, decreased appetite, and myalgia. ( 6.1 ) Pediatric Patients: Most common adverse reactions (at least 4% for CRENESSITY and greater than placebo) are headache, abdominal pain, fatigue, nasal congestion, and epistaxis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Neurocrine Biosciences, Inc. at 877-641-3461 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults with Congenital Adrenal Hyperplasia ( CAH) The safety of CRENESSITY in adults was assessed in Study 1, a randomized, double-blind, placebo-controlled study of 182 adults aged 18 to 58 years with classic CAH due to 21-hydroxylase deficiency. A total of 122 subjects received CRENESSITY 100 mg twice daily and 59 subjects received placebo twice daily for up to 24 weeks [see Clinical Studies ( 14.1 )] . Adverse Reactions Leading to Discontinuation of Treatment A total of 3% of CRENESSITY-treated subjects and no placebo-treated subjects discontinued treatment because of adverse reactions of restlessness, apathy, dyspepsia, nausea, and vomiting. Commonly Observed Adverse Reactions Adverse reactions that occurred in ≥4% of CRENESSITY-treated subjects and more frequently than in placebo-treated subjects are presented in Table 4 . Table 4 : Adverse Reactions (≥4%) in Adults with Congenital Adrenal Hyperplasia Treated with CRENESSITY and Occurring More Frequently Than in Placebo-Treated Subjects Adverse Reactions CRENESSITY (N=122) % Placebo (N=59) % Fatigue 25 15 Headache 16 15 Dizziness 8 3 Arthralgia 7 0 Back pain 6 3 Decreased appetite 4 2 Myalgia 4 3 Suicidal Ideation and Behavior Study 1 excluded subjects with active suicidal ideation with intent or plan within the six months prior to screening and those with a history of suicidal behavior within the past year, based on the Columbia-Suicide Severity Rating Scale (C-SSRS) administered at screening. The C-SSRS was administered to subjects at regular intervals during the study. Three of 122 (2.5%) CRENESSITY-treated subjects reported suicidal ideation without method, intent or plan on the C-SSRS during the 24-week double-blind treatment period compared to 1 of 59 (1.7%) placebo-treated subjects. One of the three subjects receiving CRENESSITY and the placebo-treated subject reported a lifetime history of suicidal ideation. One CRENESSITY-treated subject without a history of suicidal ideation or behavior attempted suicide during the open-label period after 320 days of treatment. Laboratory Findings Neutrophil count less than 2 x 10 3 cells/mcL occurred in 14% (17 of 120) of CRENESSITY-treated subjects, compared to 5% (3 of 58) of subjects in the placebo group. Neutrophil count less than 1 x 10 3 cells/mcL occurred in 0.8% (1 of 120) of CRENESSITY-treated subjects, compared to 1.7% subjects (1 of 58) in the placebo group. Pediatric Patients with Congenital Adrenal Hyperplasia The safety of CRENESSITY in pediatric patients was evaluated in Study 2, a randomized, double-blind placebo-controlled study of 103 pediatric subjects aged 4 to 17 years with classic CAH due to 21-hydroxylase deficiency. Pediatric subjects were randomized to receive CRENESSITY twice daily (N=69) or placebo (N=34) for 28 weeks, using weight-based dosing (50 mg twice daily via oral solution for...
Drug Interactions
7 DRUG INTERACTIONS Strong CYP3A4 I nducers: Increase CRENESSITY morning and evening dosage 2-fold. (Section 2.3 , 7.1 ) Moderate CYP3A4 Inducers: Increase CRENESSITY evening dosage 2-fold. ( 2.4 , 7.1 ) 7.1 Effects of Other Drugs on CRENESSITY Strong CYP3A4 Inducers Increase CRENESSITY morning and evening dosages 2-fold when CRENESSITY is used concomitantly with a strong CYP3A4 inducer [see Dosage and Administration ( 2.3 )]. Moderate CYP3A4 Inducers Increase CRENESSITY evening dosage 2-fold when CRENESSITY is used concomitantly with a moderate CYP3A4 inducer. Do not increase the morning dosage [see Dosage and Administration ( 2.4 )]. Mechanism of Drug Interaction and Clinical Effect CRENESSITY is a CYP3A4 substrate. Concomitant use of CRENESSITY with a strong or moderate CYP3A4 inducer decreases crinecerfont exposure [see Clinical Pharmacology ( 12.3 ) ], which may reduce CRENESSITY efficacy.
Contraindications
4 CONTRAINDICATIONS CRENESSITY is contraindicated in patients with hypersensitivity to crinecerfont or any excipients of CRENESSITY. Reactions have included throat tightness, angioedema, and generalized rash [see Warnings and Precautions ( 5.1 )] . Hypersensitivity to crinecerfont or any excipients of CRENESSITY. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data from reports of pregnancy in clinical trials with CRENESSITY 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 area under the concentration-time curve (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 ( see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. If CRENESSITY is administered during pregnancy, or if a patient becomes pregnant while receiving CRENESSITY, health care providers should report exposure to CRENESSITY by calling 1-855-CRNSITY (1-855-276-7489). Data Animal Data Crinecerfont was administered orally to pregnant rabbits at doses of 100, 500, and 1000 mg/kg/day, and to pregnant rats at doses of 150, 500, and 2000 mg/kg/day during the period of organogenesis. No crinecerfont-related malformations were observed in rats at 4-fold higher than human exposure at the MRHD based on AUC. Low incidence of poly-malformations (craniofacial defects) and slightly lower mean fetal weights were observed in rabbits treated with crinecerfont at 2-fold higher than human exposure at the MRHD based on AUC. In a pre- and postnatal developmental toxicity study, crinecerfont was administered orally to pregnant rats at doses of 15, 50,...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied CRENESSITY C apsules CRENESSITY (crinecerfont) capsules are available in the doses shown in Table 11 . Table 11. CRENESSITY Capsule Information Capsule Strength Capsule Color/Shape Capsule Marking Quantity in bottle NDC Number 25 mg Oval, orange soft gelatin capsules Printed with ‘WWV 25’ in black ink 60 70370-5025-1 50 mg Oval, two-toned orange and gold soft gelatin capsules Printed with ‘WWV 50’ in black ink 60 70370-5050-1 100 mg Oblong, gold soft gelatin capsules Printed with ‘WWV 100’ in black ink 30 70370-5100-1 CRENESSITY Oral Solution 50 mg/mL is a light yellow to orange, orange-flavored liquid. The amber polyethylene terephthalate (PET) bottle contains 30 mL oral solution (NBC 70370-5250-1). 16.2 Storage and Handling CRENESSITY Capsules Store at 15°C to 25°C (59°F to 77°F). Packaged in child-resistant HDPE bottles. Do not freeze. CRENESSITY Oral Solution Store and dispense in original container. Store CRENESSITY Oral Solution in an upright position. Store unopened bottles under refrigeration at 2°C to 8°C (36°F to 46°F). Do not freeze. Once a bottle is opened for use, it may be stored under refrigeration at 2°C to 8°C (36°F to 46°F) or at room temperature (15°C to 25°C [59°F to 77°F]) for up to 30 days. Discard any unused oral solution after 30 days of first opening the bottle. Packaged in child-resistant PET bottles. 16.1 How Supplied CRENESSITY C apsules CRENESSITY (crinecerfont) capsules are available in the doses shown in Table 11 . Table 11. CRENESSITY Capsule Information Capsule Strength Capsule Color/Shape Capsule Marking Quantity in bottle NDC Number 25 mg Oval, orange soft gelatin capsules Printed with ‘WWV 25’ in black ink 60 70370-5025-1 50 mg Oval, two-toned orange and gold soft gelatin capsules Printed with ‘WWV 50’ in black ink 60 70370-5050-1 100 mg Oblong, gold soft gelatin capsules Printed with ‘WWV 100’ in black ink 30 70370-5100-1 CRENESSITY Oral Solution 50 mg/mL is a light yellow...
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.