Crenessity crinecerfont 50 mg Capsule, 60-count — NDC 70370-5050-1 (Billing 70370-5050-01)
This is a package of 60 capsules of Crenessity crinecerfont 50 mg Capsule from Neurocrine Biosciences, Inc., no longer marketed (first marketed Dec 2024), no longer in the FDA NDC Directory. It is this product's only package size.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 086903
- GCN: 56703
- GPI-14 (Medi-Span): 30321020000130
- HICL (First Databank): 050097
- AHFS class code: 92:92.00.00
- RxCUI (RxNorm): 2701391
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
Clinical
Crinecerfont is used to control androgen (a male sex hormone) levels in adults and children with classic congenital adrenal hyperplasia (CAH; genetic disorder that impacts ability of the adrenal glad to regulate certain hormones). Crinecerfont is in a class of medications called selective corticotropin-releasing factor (CRF) type 1 receptor antagonists. It works by reducing the production of androgens.
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Crinecerfont — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
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Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $652.43 | $39,145.97 / 60 capsules |
| Medicare drug plans payPart D · Q2 2026 | $659.88 | $39,592.70 / 60 capsules |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 70370-5050-01 You're viewing this Main listing | 60 CAPSULE in 1 BOTTLE | 2024-12-13 | — | Inactivated by FDA |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Crenessity 50 mgthis 70370-5050-01 | Neurocrine | 60 capsules | — | — | Discontinued | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 12128033 ↗ | Drug substance | U-4049 | Jun 9, 2041 |
| US 12128033 ↗ | Drug substance | U-4049 | Jun 9, 2041 |
| US 12128033 ↗ | Drug substance | U-4049 | Jun 9, 2041 |
| US 10905690 ↗ | Method of use | U-4049 | Jan 21, 2035 |
| US 10905690 ↗ | Method of use | U-4049 | Jan 21, 2035 |
| US 10905690 ↗ | Method of use | U-4049 | Jan 21, 2035 |
| US 11311544 ↗ | Method of use | U-4049 | Jan 21, 2035 |
| US 11311544 ↗ | Method of use | U-4049 | Jan 21, 2035 |
| US 11311544 ↗ | Method of use | U-4049 | Jan 21, 2035 |
| US 11730739 ↗ | Method of use | U-4049 | Jan 21, 2035 |
| US 11730739 ↗ | Method of use | U-4049 | Jan 21, 2035 |
| US 11730739 ↗ | Method of use | U-4049 | Jan 21, 2035 |
| US 12582634 ↗ | Drug substance | — | Jan 12, 2043 |
| US 12582634 ↗ | Drug substance | — | Jan 12, 2043 |
| US 12582634 ↗ | Drug substance | — | Jan 12, 2043 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Dec 13, 2029 |
| ODE-503 | Orphan Drug Exclusivity (7-year) | Dec 13, 2031 |
| NCE | New Chemical Entity (5-year) | Dec 13, 2029 |
| ODE-503 | Orphan Drug Exclusivity (7-year) | Dec 13, 2031 |
| NCE | New Chemical Entity (5-year) | Dec 13, 2029 |
| ODE-503 | Orphan Drug Exclusivity (7-year) | Dec 13, 2031 |
Is there a generic version of CRENESSITY 50 MG CAPSULE?
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Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
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UNII H5ZC52369M
A synthetic ingredient made from plant-based lauric acid and polyethylene glycol. It acts as a solubilizer and emulsifier to help dissolve and blend oil and water components in the medicine.
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UNII O4446S9CRA
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UNII 506T60A25R
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UNII 15FIX9V2JP
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UNII 059QF0KO0R
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11 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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.
2.1Important 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.
2.2Recommended 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
2.3Dosage 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
2.4Dosage 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 evening meal when used concomitantly with moderate CYP3A4 inducers as shown in Table 3 [see Drug Interactions ( 7.1 )] .
Table 3 . Dosage Increase of CRENESSITY for Use with Moderate CYP3A4 Inducers in Pediatric Patients 4 Years of Age and Older Dosage Regimen with a Meal Weight Morning Dose Evening Dose 10 kg to less than 20 kg 25 mg orally 50 mg orally 20 kg to less than 55 kg 50 mg orally 100 mg orally Greater than or equal to 55 kg 100 mg orally 200 mg orally 2. 5 Administration Instructions Administer CRENESSITY orally, twice daily, with a meal in the morning and evening [see Clinical Pharmacology ( 12.3 )].
CRENESSITY Capsules Take CRENESSITY capsules orally and swallow whole with liquid. CRENESSITY Oral Solution Refer patients and/or caregivers to the Instructions for Use (IFU) for complete administration instructions. Discard any unused CRENESSITY oral solution after 30 days of first opening the bottle [see How Supplied/Storage and Handling ( 16.2 )].
2. 6 Missed Doses If a dose or do… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS CRENESSITY is available as: Capsules 25 mg oval, orange soft gelatin capsule printed with ‘WWV 25’ in black ink 50 mg oval, two-toned orange and gold soft gelatin capsule printed with ‘WWV 50’ in black ink 100 mg oblong, gold soft gelatin capsule printed with ‘WWV 100’ in black ink Oral Solution: 50 mg/mL in light yellow to orange, clear to slightly opalescent oral solution Capsules: 25 mg, 50 mg, 100 mg ( 3 ) Oral Solution: 50 mg/mL ( 3 )
⛔ 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 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Include throat tightness, angioedema, and generalized rash. If clinically significant hypersensitivity occurs, initiate appropriate therapy and discontinue CRENESSITY. ( 5.1 ) Risk of Acute Adrenal Insufficiency or Adrenal Crisis with Inadequate Concomitant Glucocorticoid Therapy: Continue glucocorticoids upon initiation of and during treatment with CRENESSITY.
Do not reduce the glucocorticoid dose below the dose required for cortisol replacement. Any adjustment of daily glucocorticoid dosage after initiation of CRENESSITY should be performed under the supervision of a health care provider. Use glucocorticoid stress doses in cases of increased cortisol need (e.g., acute intercurrent illness, serious trauma, surgical procedures).
( 5.2 )
5.1Hypersensitivity Reactions A hypersensitivity reaction, including throat tightness, angioedema, and generalized rash, occurred in a subject after 3 days of treatment with CRENESSITY. If a clinically significant hypersensitivity reaction occurs, initiate appropriate therapy and discontinue CRENESSITY. 5.
2 Risk of Acute Adrenal Insufficiency or Adrenal Crisis w ith Inadequate Concomitant Glucocorticoid Therapy Continue glucocorticoids upon initiation of and during treatment with CRENESSITY. Do not reduce the glucocorticoid dose below the dose required for cortisol replacement. Acute adrenal insufficiency or adrenal crisis, which can potentially be fatal or life-threatening, can occur in patients with underlying adrenal insufficiency who are on inadequate daily glucocorticoid doses, especially in situations associated with increased cortisol need, such as acute intercurrent illness, serious trauma, or surgical procedures.
Any adjustment of daily glucocorticoid dosage after initiation of CRENESSITY should be performed under the supervision of a health care provider. Use glucocorticoid stress doses in case of increased cortisol need (e.g., acute intercurrent illness, serious trauma, surgical procedures ). In the placebo-controlled clinical study of adults with classic CAH, the incidence of adrenal crisis was 1.6% in subjects treated with CRENESSITY and 0% in subjects treated with placebo.
In the placebo-controlled clinical study of pediatric subjects with classic CAH, there were no events of adrenal crisis.
🤒 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.
6.1Clinical 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 s… [Excerpted — this section continues on DailyMed.]
🔄 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 )
7.1Effects 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.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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, and 250 mg/kg/day during the period of organogenesis and lactation through Day 20 postpartum.
No changes in pup mortality, growth, sexual maturation, behavior, mating and fertility, or ovarian and uterine parameters were observed. The exposure in dams at the No Observed Adverse Effect Level (NOAEL) of 250 mg/kg/day was approximately 4-fold higher than human exposure at the MRHD based on AUC.
8.2Lactation Risk Summary There are no data on the presence of crinecerfont in human milk, the effects on the breastfed infant, or the effects on milk production. Crinecerfont is present in animal milk. ( see Data ) .
When a drug is present in animal milk, it is likely that the drug will be present in human milk. Infants exposed to CRENESSITY 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 CRENESSITY and any potential adverse effects on the breastfed child from CRENESSITY or from the underlying maternal condition.
Data Crinecerfont was excreted in the milk of rats, with milk-to-plasma concentration ratios ranging from 1.5 to 12. No effects on postnatal development were observed in a pre- and postnatal development study, in which female rats were treated orally with up to 250 mg/kg/day (4-fold higher than human exposure at the MRHD based on AUC) during organogenesis through lactation.
8.4Pediatric Use The safety and effectiveness of CRENESSITY 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 CRENESSITY for this indication is supported by evidence from an adequate and well-controlled study of 103 pediatric subjects (Study 2), evidence from an adequate and well-controlled study in adults with CAH (Study 1), and pharmacokinetic data from adul… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy 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, and 250 mg/kg/day during the period of organogenesis and lactation through Day 20 postpartum.
No changes in pup mortality, growth, sexual maturation, behavior, mating and fertility, or ovarian and uterine parameters were observed. The exposure in dams at the No Observed Adverse Effect Level (NOAEL) of 250 mg/kg/day was approximately 4-fold higher than human exposure at the MRHD based on AUC.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of CRENESSITY 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 CRENESSITY for this indication is supported by evidence from an adequate and well-controlled study of 103 pediatric subjects (Study 2), evidence from an adequate and well-controlled study in adults with CAH (Study 1), and pharmacokinetic data from adults and pediatric subjects [see D osage and Administration ( 2.2 ), Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.2 ) ].
The safety and effectiveness of CRENESSITY in pediatric patients less than 4 years of age have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use The clinical trial of CRENESSITY in adults with classic CAH did not enroll subjects 65 years of age and older to determine whether they respond differently from younger subjects.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Crinecerfont is a selective corticotropin-releasing factor (CRF) type 1 receptor antagonist. Crinecerfont blocks the binding of CRF to CRF type 1 receptors in the pituitary but not CRF type 2 receptors. Crinecerfont binding to CRF type 1 receptors inhibits adrenocorticotropic hormone (ACTH) secretion from the pituitary, thereby reducing ACTH-mediated adrenal androgen production.
12.2Pharmacodynamics Exposure-Response Relationships Model based exposure-response analyses for adults and pediatric patients with CAH demonstrated that, within the studied exposures of CRENESSITY in Phase 3 trials, relatively flat exposure-response relationships were observed for androstenedione reduction from baseline to Week 4 for both adults and pediatric patients and percent glucocorticoid daily dose reduction from baseline to Week 24 for adults and to Week 28 for pediatric patients. Adrenocorticotropic Hormone (ACTH) Reduction In 8 adults with classic CAH (NCT0352886) who received the recommended CRENESSITY dosage for 2 weeks, the median percent reduction from baseline in ACTH was 62%.
In the Phase 3 clinical trials of adults and pediatric patients with classic CAH, administration of the recommended CRENESSITY dosage for 4 weeks during the initial glucocorticoid stable period led to a reduction in ACTH levels. In Study 1, the median percent reduction from baseline to Week 4 in ACTH was 65%. In Study 2, the median percent reduction from baseline to Week 4 in ACTH was 72%.
Cardiac Electrophysiology At a dose 4 times the maximum approved recommended dosage, CRENESSITY does not prolong the QT interval to any clinically relevant extent.
12.3Pharmacokinetics Crinecerfont maximum plasma concentration (C max ) and area under the time concentration curve (AUC 0-24 hours ) increases dose-proportionally over the approved recommended dosage range. Upon twice daily dosing, steady state conditions are achieved in approximately 7 days with an accumulation ratio of 1.4. Absorption Crinecerfont median time to reach C max (T max ) is 4 hours following oral administration of CRENESSITY.
No clinically significant differences in crinecerfont C max or AUC were observed following administration of CRENESSITY oral capsules and oral solution. Steady state exposures for crinecerfont in adults and pediatric patients following oral administration of CRENESSITY are presented in Table 6 . Table 6 .
Geometric Mean (CV%) for AUC 24,ss and C max in Adults and Pediatric Patients with Classic Congenital Adrenal Hyperplasia Following Oral Administration of CRENESSITY Parameter Geometric Mean (CV%) Study 1 (adults) Study 2 (pediatrics) AUC 24hr,ss (ng*h/mL) Dose: 100 mg bid 72846 (51%) Dose 100 mg bid (≥ 55 kg) Dose 50 mg bid (≥ 20 to < 55 kg) 74693 (48%) 47062 (51%) C max (ng/mL) 4231 (46%) Dose 100 mg bid (≥ 55 kg) Dose 50 mg bid (≥ 20 to < 55 kg) 4555 (43%) 2887 (48%) CV%, coefficient of variation expressed as a percentage; bid, twice daily; steady-state exposure parameters are generated from simulation of 500 subjects based on population pharmacokinetic modeling and weight band appropriate formulation Effect of Food Following administration of CRENESSITY capsule, crinecerfont C max increased 4.9-fold and AUC increased 3.3-fold with a high-fat meal (800 to 1000 calories, 50% fat), compared to fasted conditions [see Dosage and Administration ( 2.2 )] .
Following administration of CRENESSITY oral solution, crinecerfont C max increased 8.6-fold and AUC increased 8.3-fold with a high-fat meal (800 to 1000 calories, 50% fat), compared to fasted conditions [see Dosage and Administration ( 2.2 )] Distribution Mean apparent volume of distribution (CV%) of crinecerfont in adults with CAH is 852 L (31%). Crinecerfont plasma protein binding is greater than or equal to 99.9%. Elimination Crinecerfont’s effective half-life is approximately 14 hours with a mean (CV%) apparent clearance of
3.5L/h (37%). Metabolism Crinecerfont is metabolized… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Crinecerfont is a selective corticotropin-releasing factor (CRF) type 1 receptor antagonist. Crinecerfont blocks the binding of CRF to CRF type 1 receptors in the pituitary but not CRF type 2 receptors. Crinecerfont binding to CRF type 1 receptors inhibits adrenocorticotropic hormone (ACTH) secretion from the pituitary, thereby reducing ACTH-mediated adrenal androgen production.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How 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).
16.2Storage 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.
16.1How 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).
📦 Storage and Handling ▾
16.2Storage 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.
📋 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
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patients and/or caregivers to read the FDA-approved patient labeling ( Patient Information leaflet and CRENESSITY oral solution IFU, if applicable). Administration Information Counsel patients that CRENESSITY must be taken with a meal, without regard to fat or caloric content [see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )] . Drug Interactions Inform patients that the CRENESSITY dosage will need to be increased if they are taking strong or moderate CYP3A4 inducers [see Dosage and Administration ( 2.3 , 2.4 ), Drug Interactions ( 7.1 )].
Hypersensitivity Reactions Advise patients to seek prompt medical attention if signs or symptoms of hypersensitivity reactions occur. Advise patients who have had signs or symptoms of systemic hypersensitivity reactions to CRENESSITY that they should not receive CRENESSITY [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] . Acute Adrenal Insufficiency or Adrenal Crisis w ith Inadequate Concomitant Glucocorticoid Therapy Inform patients that they should continue glucocorticoids when taking CRENESSITY.
Counsel patients that any adjustment of glucocorticoid doses should be done under the guidance of their health care provider. Counsel patients about the continued need for stress dose glucocorticoids during times of increased cortisol need (e.g., during illness) [see Warnings and Precautions ( 5.2 )]. Pregnancy Advise women who are exposed to CRENESSITY during pregnancy that there is a pregnancy safety study [see Use in Specific Populations ( 8.1 )] .
For information on CRENESSITY, visit www.CRENESSITY.com or call 1-855-CRNSITY (1-855-276-7489). Distributed by: Neurocrine Biosciences, Inc., San Diego, CA 92130, U.S.A. CRENESSITY is a trademark of Neurocrine Biosciences, Inc.
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Crinecerfont maximum plasma concentration (C max ) and area under the time concentration curve (AUC 0-24 hours ) increases dose-proportionally over the approved recommended dosage range. Upon twice daily dosing, steady state conditions are achieved in approximately 7 days with an accumulation ratio of 1.4. Absorption Crinecerfont median time to reach C max (T max ) is 4 hours following oral administration of CRENESSITY.
No clinically significant differences in crinecerfont C max or AUC were observed following administration of CRENESSITY oral capsules and oral solution. Steady state exposures for crinecerfont in adults and pediatric patients following oral administration of CRENESSITY are presented in Table 6 . Table 6 .
Geometric Mean (CV%) for AUC 24,ss and C max in Adults and Pediatric Patients with Classic Congenital Adrenal Hyperplasia Following Oral Administration of CRENESSITY Parameter Geometric Mean (CV%) Study 1 (adults) Study 2 (pediatrics) AUC 24hr,ss (ng*h/mL) Dose: 100 mg bid 72846 (51%) Dose 100 mg bid (≥ 55 kg) Dose 50 mg bid (≥ 20 to < 55 kg) 74693 (48%) 47062 (51%) C max (ng/mL) 4231 (46%) Dose 100 mg bid (≥ 55 kg) Dose 50 mg bid (≥ 20 to < 55 kg) 4555 (43%) 2887 (48%) CV%, coefficient of variation expressed as a percentage; bid, twice daily; steady-state exposure parameters are generated from simulation of 500 subjects based on population pharmacokinetic modeling and weight band appropriate formulation Effect of Food Following administration of CRENESSITY capsule, crinecerfont C max increased 4.9-fold and AUC increased 3.3-fold with a high-fat meal (800 to 1000 calories, 50% fat), compared to fasted conditions [see Dosage and Administration ( 2.2 )] .
Following administration of CRENESSITY oral solution, crinecerfont C max increased 8.6-fold and AUC increased 8.3-fold with a high-fat meal (800 to 1000 calories, 50% fat), compared to fasted conditions [see Dosage and Administration ( 2.2 )] Distribution Mean apparent volume of distribution (CV%) of crinecerfont in adults with CAH is 852 L (31%). Crinecerfont plasma protein binding is greater than or equal to 99.9%. Elimination Crinecerfont’s effective half-life is approximately 14 hours with a mean (CV%) apparent clearance of
3.5L/h (37%). Metabolism Crinecerfont is metabolized primarily by CYP3A4 and to a lesser extent by CYP2B6 in vitro. Additionally, CYP2C8 and CYP2C19 may also have minor contributions to crinecerfont metabolism.
Excretion Following a single oral 100 mg dose of radiolabeled crinecerfont, approximately 47.3% (2.7% as unchanged) of the dose was recovered in feces and 2% (amount as unchanged is undetectable) in urine. Specific Populations No clinically significant differences in the pharmacokinetics of crinecerfont were observed based on age (range: 5 to 54 years), sex (58.7% male), race (4.8% Asian, 9.7% Black, 77.5% White), mild to severe hepatic impairment (Child Pugh Class A to C), or mild to moderate renal impairment (estimated glomerular filtration rate: equal to or greater than 44 mL/min/1.73 m 2 ; CKD-EPI 2009 formula for adults and bedside Schwartz formula for pediatric patients).
Crinecerfont has not been studied in patients with severe renal impairment or end-stage renal disease . Drug Interaction Studies Clinical Studies Effect of Strong CYP3A4 Inducers on Crinecerfont: Crinecerfont C max decreased by 23% and AUC decreased by 62% following concomitant use with rifampin (strong CYP3A4 inducer) [see Dosage and Administration ( 2.3 ) and Drug Interactions ( 7.1 )] . Effect of Strong CYP3A4 Inhibitors on Crinecerfont: Crinecerfont C max and AUC increased by 25% and 45%, respectively, when used concomitantly with ketoconazole (strong CYP3A4 inhibitor).
Effect of Crinecerfont on CYP3A Substrates: No clinically significant differences in the pharmacokinetics of midazolam (CYP3A4 substrate) were observed when co-administered with crinecerfont. Concomitant use of crinecerfont did not affect the pharmacokinetics of or… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Exposure-Response Relationships Model based exposure-response analyses for adults and pediatric patients with CAH demonstrated that, within the studied exposures of CRENESSITY in Phase 3 trials, relatively flat exposure-response relationships were observed for androstenedione reduction from baseline to Week 4 for both adults and pediatric patients and percent glucocorticoid daily dose reduction from baseline to Week 24 for adults and to Week 28 for pediatric patients. Adrenocorticotropic Hormone (ACTH) Reduction In 8 adults with classic CAH (NCT0352886) who received the recommended CRENESSITY dosage for 2 weeks, the median percent reduction from baseline in ACTH was 62%.
In the Phase 3 clinical trials of adults and pediatric patients with classic CAH, administration of the recommended CRENESSITY dosage for 4 weeks during the initial glucocorticoid stable period led to a reduction in ACTH levels. In Study 1, the median percent reduction from baseline to Week 4 in ACTH was 65%. In Study 2, the median percent reduction from baseline to Week 4 in ACTH was 72%.
Cardiac Electrophysiology At a dose 4 times the maximum approved recommended dosage, CRENESSITY does not prolong the QT interval to any clinically relevant extent.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Adults with Classic Congenital Adrenal Hyperplasia The efficacy of CRENESSITY to reduce androgen levels and enable a reduced glucocorticoid dose while maintaining androgen control in adults with classic CAH was evaluated in a randomized, double-blind, placebo-controlled study (Study 1; NCT#04490915). This study enrolled 182 adults with classic CAH due to 21- hydroxylase deficiency on supraphysiological glucocorticoid doses and with androgen concentrations in the normal range or with inadequate androgen control.
Subjects were randomized to receive CRENESSITY 100 mg twice daily (N=122) or placebo (N=60) for 24 weeks. During the first 4 weeks of CRENESSITY treatment, subjects maintained a stable glucocorticoid regimen except for stress dosing as needed. During Weeks 4 to 12, the glucocorticoid dose was reduced as frequently as every 2 weeks without regard to androstenedione levels, with the goal to achieve a glucocorticoid dose of 8 to 10 mg/m 2 /day in hydrocortisone dose equivalents adjusted for body surface area by Week 12.
From Weeks 12 to 20, the glucocorticoid dose was further adjusted, if needed, to achieve androstenedione control by Week 24. The mean (range) age was 31 (18 to 58) years, 51% were male, 90% were White, and 8% were Hispanic or Latino. At baseline, the mean (SD) glucocorticoid total daily dose in hydrocortisone equivalents was 32 (9) mg/day (18 [5] mg/m 2 /day), with mean (SD) androstenedione levels of 620 (729) ng/dL prior to the morning glucocorticoid dose.
The efficacy of CRENESSITY was assessed by the least-squares (LS) mean (SEM) percent change from baseline in the total glucocorticoid daily dose while androstenedione was controlled (≤120% of baseline or ≤upper limit of normal [ULN]) after 24 weeks. The LS mean percent change from baseline in daily glucocorticoid dose was statistically significantly greater in the CRENESSITY group at -27% compared to -10% in the placebo group, as shown in Table 7 . Table 7 : Primary Change F rom Baseline in Glucocorticoid Daily Dose While Maintaining Androstenedione Control at Week 24 in Adults with Classic Congenital Adrenal Hyperplasia (Study 1) Treatment Group Mean (SD) Baseline (mg/m 2 /day) LS Mean (SEM) Percent Change F rom Baseline (%) Placebo- S ubtracted LS Mean Difference ( 95% CI ) (%) Glucocorticoid Daily Dose* CRENESSITY N=122 18 (5) -27 (2) -17 (-24, -10) p<0.0001 Placebo N=60 18 (6) -10 (3) CI=confidence interval; LS mean=least-squares mean; SD=standard deviation; SEM=standard error of the mean * In hydrocortisone equivalents (4x equivalency factor for (methyl)predniso(lo)ne, 60x for dexamethasone) adjusted for body surface area.
At Week 24, there was a statistically significantly greater percentage of subjects achieving a reduction to a physiologic glucocorticoid daily dose (≤11 mg/m 2 /day hydrocortisone equivalents) while androstenedione was controlled (≤120% of baseline or ≤ULN) with CRENESSITY compared to placebo (63% vs 18%, p<0.0001). At Week 4, following a treatment period at a stable glucocorticoid dose regimen, the LS mean change from baseline in serum androstenedione in the CRENESSITY group was statistically significantly different at -299 ng/dL compared to the LS mean increase from baseline in the placebo group of 46 ng/dL, as shown in Table 8 .
Table 8 : Change F rom Baseline in Serum Androstenedione (ng/dL) at Week 4* in Adults with Classic Congenital Adrenal Hyperplasia (Study 1) Treatment Group Mean (SD) Baseline LS Mean (SEM) Change from Baseline Placebo-subtracted LS Mean Difference (95% CI) Serum Androstenedione (ng/dL) † CRENESSITY N=122 634 (796) -299 (38) -345 (-457, -232) p<0.0001 Placebo N=60 590 (572) 46 (51) CI=confidence interval; LS mean=least-squares mean; SD=standard deviation; SEM=standard error of the mean * End of glucocorticoid stable period. † Obtained prior to the morning glucocorticoid dose.
14.2Pediatric Patients with Classic Congenital Adrenal Hyperplasia The efficacy of CRENESSITY to improve… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In a 2-year carcinogenicity study, rats were administered daily crinecerfont doses of 5, 15, and 100 mg/kg/day via oral gavage. An increased incidence of thyroid follicular cell combined adenomas and carcinomas was observed in female rats at the 100 mg/kg/day dose level (approximately 4-fold higher than human exposure at the MRHD based on AUC). Thyroid follicular cell tumors can occur in rats from excessive thyroid stimulating hormone (TSH) secondary to liver enzyme induction, which is not thought to commonly occur in humans.
No evidence of increased tumorigenicity was seen in male rats up to approximately 5-fold higher than human exposure at the MRHD based on AUC or in female rats up to approximately 2-fold higher than human exposure at the MRHD based on AUC. In a 6-month study in Tg.rasH2 mice, daily crinecerfont doses of 15, 50, 500, and 1500 mg/kg/day were administered via oral gavage. Crinecerfont did not increase the incidence of tumors in male or female transgenic mice (approximately 4-fold higher than human exposure at the MRHD based on AUC).
Mutagenesis Crinecerfont was not mutagenic in the in vitro bacterial reverse mutation test (Ames) or clastogenic in the in vitro mammalian chromosomal aberrations assay in human peripheral blood lymphocytes or in the in vivo rat bone marrow micronucleus assay. Impairment of Fertility There were no crinecerfont-related effects on male or female fertility or female reproductive performance in rats treated orally with up to 1000 mg/kg/day crinecerfont at 2-fold higher than human exposure at the MRHD by AUC exposure.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In a 2-year carcinogenicity study, rats were administered daily crinecerfont doses of 5, 15, and 100 mg/kg/day via oral gavage. An increased incidence of thyroid follicular cell combined adenomas and carcinomas was observed in female rats at the 100 mg/kg/day dose level (approximately 4-fold higher than human exposure at the MRHD based on AUC). Thyroid follicular cell tumors can occur in rats from excessive thyroid stimulating hormone (TSH) secondary to liver enzyme induction, which is not thought to commonly occur in humans.
No evidence of increased tumorigenicity was seen in male rats up to approximately 5-fold higher than human exposure at the MRHD based on AUC or in female rats up to approximately 2-fold higher than human exposure at the MRHD based on AUC. In a 6-month study in Tg.rasH2 mice, daily crinecerfont doses of 15, 50, 500, and 1500 mg/kg/day were administered via oral gavage. Crinecerfont did not increase the incidence of tumors in male or female transgenic mice (approximately 4-fold higher than human exposure at the MRHD based on AUC).
Mutagenesis Crinecerfont was not mutagenic in the in vitro bacterial reverse mutation test (Ames) or clastogenic in the in vitro mammalian chromosomal aberrations assay in human peripheral blood lymphocytes or in the in vivo rat bone marrow micronucleus assay. Impairment of Fertility There were no crinecerfont-related effects on male or female fertility or female reproductive performance in rats treated orally with up to 1000 mg/kg/day crinecerfont at 2-fold higher than human exposure at the MRHD by AUC exposure.
📄 Patient Package Insert ▾
PATIENT INFORMATION CRENESSITY® (kreh NEH sih tee) (CRINECERFONT) CAPSULES AND ORAL SOLUTION What is CRENESSITY? CRENESSITY is a prescription medicine used together with glucocorticoids (steroids) to control androgen (testosterone-like hormone) levels in adults and children 4 years of age and older with classic congenital adrenal hyperplasia (CAH). It is not known if CRENESSITY is safe and effective in children younger than 4 years of age.
Do not take CRENESSITY if you: are allergic to crinecerfont, or any of the ingredients in CRENESSITY. See the end of this Patient Information leaflet for a complete list of ingredients in CRENESSITY. Before taking CRENESSITY, tell your health care provider about all of your medical conditions , including if you: are pregnant or plan to become pregnant.
It is not known if CRENESSITY will harm your unborn baby. If you become pregnant while taking CRENESSITY, tell your health care provider right away. There is a pregnancy safety study for women who become pregnant during treatment with CRENESSITY. are breastfeeding or plan to breastfeed.
It is not known if CRENESSITY passes into your breast milk. Talk to your health care provider about the best way to feed your baby during treatment with CRENESSITY. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.
Taking CRENESSITY with certain other medicines may cause your CRENESSITY to not work as well. Do not start any new medicines while taking CRENESSITY without talking to your health care provider first. How should I take CRENESSITY ?
Take CRENESSITY exactly as your health care provider tells you to. Your health care provider will tell you how much CRENESSITY to take and when to take it. Do not stop taking CRENESSITY without talking to your health care provider first.
While your health care provider may lower your glucocorticoids (steroids), you should continue to take glucocorticoids (steroids) to treat adrenal insufficiency, including stress dose steroids (such as when your body may be under stress from fever, infection or surgery). Do not change your daily glucocorticoid (steroid) dose without talking to your health care provider. See “ What are the possible side effects of CRENESSITY? ” Take CRENESSITY by mouth 2 times each day, in the morning and evening with a meal.
Swallow CRENESSITY capsules whole with liquid. Tell your health care provider if you cannot swallow the capsule whole. Your healthcare provider may need to switch you to CRENESSITY oral solution.
If your health care provider prescribes CRENESSITY oral solution, you should use the oral dosing syringe that your pharmacist will give you to measure and take the correct dose. See the Instructions for Use for CRENESSITY oral solution for more information. If you miss a dose of CRENESSITY, take it as soon as you remember (even if it is almost time for your next dose).
Take the next dose at your regular time. What are the possible side effects of CRENESSITY? CRENESSITY may cause serious side effects , including: Allergic reactions .
Symptoms of an allergic reaction include tightness of the throat, trouble breathing or swallowing, swelling of the lips, tongue, or face, and rash. If you have an allergic reaction to CRENESSITY, get emergency medical help right away and stop taking CRENESSITY. Risk of Sudden Adrenal Insufficiency or Adrenal Crisis with Too Little Glucocorticoid (Steroid) Medicine .
Sudden adrenal insufficiency or adrenal crisis can happen in people with congenital adrenal hyperplasia who are not taking enough glucocorticoid (steroid) medicine. You should continue taking your glucocorticoid (steroid) medicine during treatment with CRENESSITY. Certain conditions such as infection, severe injury, or shock may increase your risk for sudden adrenal insufficiency or adrenal crisis.
Tell your health care provider if you get a severe injury, infection, illness, or have any planned surgery… [Excerpted — this section continues on DailyMed.]
📖 Instructions for Use ▾
INSTRUCTIONS FOR USE CRENESSITY TM (kreh NEH sih tee) (crinecerfont) oral solution 50 mg/mL Read this Instructions for Use for important information you need to know before taking CRENESSITY oral solution for the first time and each time you get a refill. There may be new information. This information does not take the place of talking to your health care provider about your medical condition or treatment.
Important information: Take CRENESSITY oral solution exactly as your health care provider tells you to. Your health care provider will tell you how much CRENESSITY oral solution to take and when to take it. CRENESSITY oral solution should be taken with a meal in the morning and evening.
Always use the oral syringe provided by your pharmacist to make sure you measure the right amount of CRENESSITY oral solution. Use CRENESSITY oral solution within 30 days of first opening the bottle. After 30 days of first opening the bottle, throw away (dispose of) any CRENESSITY oral solution that has not been used.
Do not stop taking CRENESSITY oral solution without talking to your health care provider first. See the Patient Information Leaflet that comes with CRENESSITY for more information. Supplies not included in the package: Press-in bottle adapter Oral syringes You must get a press-in bottle adapter and oral syringe from your pharmacist.
Your pharmacist can help you choose the right press-in bottle adapter and oral syringes to use with CRENESSITY oral solution. Call your pharmacist right away if you do not have a press-in bottle adapter and the right oral syringe to use with your CRENESSITY oral solution. How should I prepare and take CRENESSITY oral solution?
1. Gather the supplies (see Figure A) : • CRENESSITY oral solution bottle • Press-in bottle adapter • Oral syringe Figure A 2. Inspect CRENESSITY.
Check the pharmacy label to make sure the medicine name and dose are correct. Check the oral solution bottle, oral syringe, and press-in bottle adapter for signs of damage. Do not use CRENESSITY oral solution bottle, oral syringe, or press-in bottle adapter if it appears to be damaged or tampered with.
Contact your pharmacist or health care provided. 3. Prepare CRENESSITY oral solution. a.
Remove the child-resistant cap by pressing it down while twisting it to the left (counterclockwise) (See Figure B ). b. Carefully puncture and peel off the seal from the bottle (See Figure C ). c. First time use of the bottle only .
While holding the bottle firmly with one hand, use the thumb on your other hand to push the press-in bottle adapter into the bottle as far as it will go using constant pressure (see Figure D ). Do not remove the press-in bottle adapter after it has been inserted. Figure B Figure C Figure D 4.
Prepare the dose. a. Push in the plunger of the oral syringe as far as it will go (see Figure E ). If the oral syringe comes with a cap, pull off the syringe cap.
Figure E b. Insert the tip of the oral syringe into the press-in bottle adapter, then with the oral syringe still inserted, turn the bottle upside down (see Figure F ). Figure F c.
Slowly pull the plunger of the oral syringe until the part of the plunger that is touching the liquid is even with the marking of your prescribed dose (see Figure G ). Note : Slowly push the plunger to return any large air bubbles back to the bottle and repeat the prior step until the air bubbles are gone. Figure G d.
When you have measured the correct amount of CRENESSITY, keep the oral syringe inserted in the bottle and turn the bottle and oral syringe right side up. Hold the oral syringe from the middle, then carefully remove it from the bottle (see Figure H ). Do not touch the plunger to avoid oral solution accidentally coming out of the syringe before you are ready to give the medicine.
Figure H 5. Give a dose of CRENESSITY oral solution. a. Place the tip of the oral syringe inside your mouth and point it towards the inside of the cheek. b.
Slowly push the plunger all the way down to give… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL NDC 70370-5025-1 Crenessity (crinecerfont) capsules 25 mg 60 Capsules Rx only PRINCIPAL DISPLAY PANEL NDC 70370-5025-1 Crenessity (crinecerfont) capsules 25 mg 60 Capsules Rx only
PRINCIPAL DISPLAY PANEL NDC 70370-5050-1 Crenessity (crinecerfont) capsules 50 mg 60 Capsules Rx only PRINCIPAL DISPLAY PANEL NDC 70370-5050-1 Crenessity (crinecerfont) capsules 50 mg 60 Capsules Rx only
PRINCIPAL DISPLAY PANEL NDC 70370-5100-1 Crenessity (crinecerfont) capsules 100 mg 30 Capsules Rx only PRINCIPAL DISPLAY PANEL NDC 70370-5100-1 Crenessity (crinecerfont) capsules 100 mg 30 Capsules Rx only
PRINCIPAL DISPLAY PANEL NDC 70370-5250-1 Crenessity (crinecerfont) oral solution 50 mg/mL 30 mL Rx only PRINCIPAL DISPLAY PANEL NDC 70370-5250-1 Crenessity (crinecerfont) oral solution 50 mg/mL 30 mL Rx only
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| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |