Carbamoyl Phosphate Synthetase 1 Activator

Carglumic Acid

Approved 13 Oct 2021OralTablet, for suspension

The FDA lists this product in 2 strengths and forms.

Indications

Carglumic acid tablets for oral suspension is a carbamoyl phosphate synthetase 1 (CPS 1) activator indicated in pediatric and adult patients as: Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency. (1.1) Maintenance therapy for the treatment of chronic hyperammonemia due to NAGS deficiency. (1.1)

1.1Acute and Chronic

Hyperammonemia due to N-acetylglutamate Synthase (NAGS) Deficiency Carglumic acid tablets for oral suspension are indicated in adult and pediatric patients as: Adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to NAGS deficiency. Maintenance therapy for the treatment of chronic hyperammonemia due to NAGS deficiency.

Contraindications

None None. (4)

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Although rare case reports of Carglumic acid tablets for oral suspension use in pregnant women are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, untreated NAGS deficiency can result in irreversible neurologic damage and death in pregnant women [see Clinical Considerations]. In an animal reproduction study, decreased survival and growth occurred in offspring born to rats that received carglumic acid at a dose approximately 38 times the maximum reported human maintenance dose.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, 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. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnant women with urea cycle disorders may experience an increase in catabolic stress which can trigger a hyperammonemic crisis both in the intrapartum and in the post-partum (3-14 days post-partum) periods.

Indications

1.1Acute and Chronic

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

NAGS deficiency: Most common adverse reactions (≥13%) are vomiting, abdominal pain, pyrexia, tonsillitis, anemia, diarrhea, ear infection, infections, nasopharyngitis, hemoglobin decreased, and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Eton Pharmaceuticals, Inc. at 1-855-224-0233, 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. Acute and Chronic Hyperammonemia due to NAGS Deficiency In a retrospective case series of 23 NAGS deficiency patients treated with Carglumic acid tablets for oral suspension, 17 of the 23 patients reported an adverse reaction.

The most common adverse reactions (occurring in ≥ 13% of patients) were vomiting, abdominal pain, pyrexia, tonsillitis, anemia, diarrhea, ear infection, infections, nasopharyngitis, hemoglobin decreased, and headache. Table 1 summarizes adverse reactions occurring in 2 or more patients treated with Carglumic acid tablets for oral suspension. Table 1: Adverse Reactions Reported in ≥ 2 Patients with NAGS deficiency Treated with Carglumic acid tablets for oral suspension in the Retrospective Case Series Adverse Reaction Number of Patients (N) (%) Vomiting 6 (26) Abdominal pain 4 (17) Pyrexia 4 (17) Tonsillitis 4 (17) Anemia 3 (13) Diarrhea 3 (13) Ear infection 3 (13) Infections 3 (13) Nasopharyngitis 3 (13) Hemoglobin decreased 3 (13) Headache 3 (13) Dysgeusia 2 (9) Asthenia 2 (9) Hyperhidrosis 2 (9) Influenza 2 (9) Pneumonia 2 (9) Weight decreased 2 (9) Anorexia 2 (9) Somnolence 2 (9) Rash 2 (9)

6.2Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Carglumic acid tablets for oral suspension. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure. Psychiatric disorders : mania Skin and subcutaneous tissue disorders : pruritus, rash including rash erythematous, rash maculopapular, rash pustular

Carglumic Acid

Indications

1.1Acute and Chronic

Contraindications

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Two medicines in one question?

Carglumic Acid

Indications

1.1Acute and Chronic

Contraindications

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Two medicines in one question?

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information

At a glance