Berotralstat

Berotralstat is a plasma kallikrein inhibitor that binds to plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE.

• ORLADEYO ® is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 2 years of age and older. ORLADEYO is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 2 years and older.

• None. None.contraindicated

Recommended dosage in adult and pediatric patients aged 12 years and older: 150 mg capsule orally once daily with food. ( 2.1 ) Recommended dosage in pediatric patients aged 2 to less than 12 years is based on body weight as follows ( 2.2 , 2.5 ): Weight Recommended Dosage (oral pellets) Administration Instructions 12 kg to less than 24 kg 72 mg once daily Pour directly in mouth and swallow immediately with non-acidic liquid, or, Sprinkle over 1 tablespoon (15 mL) of non-acidic soft food and consume immediately. A meal should be consumed just before or after administration. 24 kg to less than 32 kg 96 mg once daily 32 kg to less than 40 kg 108 mg once daily 40 kg or greater 132 mg once daily See full prescribing information for recommended dosage in patients with hepatic impairment and dosage modification in patients with persistent gastrointestinal adverse reactions. ( 2.3 , 2.4 ) 2.1 Recommended Dosage in Adults and Pediatric Patients 12 Years of Age and Older The recommended dosage of ORLADEYO capsules for adults and pediatric patients 12 years of age and older is 150 mg taken orally once daily with food. 2.2 Recommended Dosage in Pediatric Patients 2 Years to Less than 12 Years of Age The recommended dosage of ORLADEYO oral pellets for pediatric patients 2 years to less than 12 years of age is based on the patient's body weight as provided in Table 1. Take ORLADEYO orally with food (a meal should be consumed just before or after dosing) [see Dosage and Administration (2.5) ] .

An increase in QTc interval prolongation can occur at dosages higher than the recommended dosage. Additional doses or doses of ORLADEYO higher than the recommended dosage are not recommended. ( 5.1 ) 5.1 Risk of QTc Interval Prolongation with Higher-Than-Recommended Dosages ORLADEYO should not be used for treatment of acute attacks of HAE. Additional doses or doses of ORLADEYO higher than the recommended dosage are not recommended. An increase in QTc interval was observed in adults at dosages higher than 150 mg once daily and was concentration dependent [see Dosage and Administration (2) and Clinical Pharmacology (12.2) ] .

The following clinically significant adverse reaction is described elsewhere in the labeling: QTc Interval Prolongation [see Warnings and Precautions (5.1) ] . Most common adverse reactions (≥10%) are abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact BioCryst Pharmaceuticals, Inc. at 1-833-633-2279 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. Adverse Reactions in Adult and Pediatric Patients 12 Years of Age and Older The safety of ORLADEYO is primarily based on 24-week (Part 1) data from a 3-part, double-blind, parallel-group, placebo-controlled trial (Trial 1) in 120 patients with Type I or II HAE who were randomized and dosed with either ORLADEYO 110 mg, 150 mg, or placebo, once daily with food. After Week 24, patients who continued in the study received active treatment through 48 weeks. In Trial 1, a total of 81 patients aged 12 years and older with HAE received at least one dose of ORLADEYO in Part 1. Overall, 66% of patients were female and 93% of patients were White with a mean age of 41.6 years.

Avoid use of ORLADEYO in pediatric patients 2 years to less than 12 years of age with severe renal impairment. ( 8.6 ) ORLADEYO is not recommended in patients with end-stage renal disease. ( 8.6 ) 8.1 Pregnancy Risk Summary There are insufficient data in pregnant women available to inform drug-related risks with ORLADEYO use in pregnancy. Based on animal reproduction studies, no evidence of structural alterations was observed when berotralstat was administered orally to pregnant rats and rabbits during organogenesis at doses up to approximately 10- and 2-times, respectively, the maximum recommended human daily dose (MRHDD) in adults on an AUC basis (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. 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. Data Animal Data In animal reproduction studies, oral administration of berotralstat to pregnant rats and rabbits during the period of organogenesis did not cause fetal structural alterations. The berotralstat dose in rats and rabbits was up to approximately 10- and 2-times, respectively, the MRHDD in adults (on an AUC basis at maternal doses of 75 and 100 mg/kg/day, respectively).

Metabolism

Following oral administration of berotralstat 150 mg once daily in adults, the geometric mean steady-state C max is 158 ng/mL (range: 110 to 234 ng/mL) and steady-state area under the curve over the dosing interval (AUC tau ) is 2770 ng*hr/mL (range: 1880 to 3790 ng*hr/mL). Following oral administration of berotralstat 110 mg once daily, the geometric mean steady-state C max is 97.8 ng/mL (range: 63 to 235 ng/mL) and steady-state AUC tau is 1600 ng*hr/mL (range: 950 to 4170 ng*hr/mL).

• Dec 3, 2020NDANDA214094Biocryst
• Dec 11, 2025NDANDA219776Biocryst

1. 1Hereditary Angioedema234—
2. 2Nausea57—
3. 3Diarrhoea55—
4. 4Drug Ineffective53—
5. 5Headache47—
6. 6Abdominal Pain46—
7. 7Condition Aggravated44—
8. 8Gastrointestinal Disorder42—
9. 9Vomiting38—
10. 10Fatigue37—
11. 11Malaise36—
12. 12Covid-1935—
13. 13Abdominal Pain Upper33—
14. 14Dizziness29—
15. 15Abdominal Distension28—

The 10 most recently updated of 12 ClinicalTrials.gov registrations naming Berotralstat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Berotralstat Treatment in Children With Hereditary Angioedema
  Active not recruiting · Phase 3 · Interventional · 29 enrolled · BioCryst Pharmaceuticals
  NCT05453968updated 2026-02-25
• Open-label Berotralstat Access to HAE Patients Previously Enrolled in Berotralstat Studies
  Enrolling by invitation · Phase 3 · Interventional · 139 enrolled · BioCryst Pharmaceuticals
  NCT04933721updated 2025-12-23
• Study to Evaluate the Efficacy and Safety of BCX7353 as an Oral Treatment for the Prevention of HAE Attacks in Japan
  Completed · Phase 3 · Interventional · 19 enrolled · BioCryst Pharmaceuticals
  NCT03873116updated 2024-07-19
• Efficacy and Safety Study of BCX7353 as an Oral Treatment for the Prevention of Attacks in HAE
  Completed · Phase 3 · Interventional · 121 enrolled · BioCryst Pharmaceuticals
  NCT03485911updated 2023-06-26
• A Long Term Safety Study of BCX7353 in Hereditary Angioedema
  Completed · Phase 2 · Phase 3 · Interventional · 387 enrolled · BioCryst Pharmaceuticals
  NCT03472040updated 2023-06-18
• Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema
  Completed · Phase 2 · Interventional · 58 enrolled · BioCryst Pharmaceuticals
  NCT03240133updated 2021-04-01
• Efficacy and Safety of BCX7353 to Prevent Angioedema Attacks in Subjects With Hereditary Angioedema
  Completed · Phase 2 · Interventional · 75 enrolled · BioCryst Pharmaceuticals
  NCT02870972updated 2021-03-23
• Oral Berotralstat Expanded Access Program
  Approved for marketing · Expanded access · BioCryst Pharmaceuticals
  NCT04428632updated 2020-12-11
• A Relative Bioavailability Study of Two Formulations of BCX7353
  Completed · Phase 1 · Interventional · 24 enrolled · BioCryst Pharmaceuticals
  NCT03202784updated 2020-01-27
• A Drug-Drug Interaction Study to Evaluate Drug Transporter Interactions
  Completed · Phase 1 · Interventional · 54 enrolled · BioCryst Pharmaceuticals
  NCT03136237updated 2017-10-26

Frequently asked questions

How does Berotralstat work?

Berotralstat is a plasma kallikrein inhibitor that binds to plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE.

What is Berotralstat used for?

According to FDA labeling, Berotralstat carries indications including: ORLADEYO ® is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 2 years of age and older. ORLADEYO is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 2 years and older.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Berotralstat?

Berotralstat is classified as Drugs used in hereditary angioedema, Plasma Kallikrein Inhibitor, Cytochrome P450 2D6 Inhibitors, Cytochrome P450 3A4 Inhibitors, Kallikrein Inhibitors, P-Glycoprotein Inhibitors.

What are the brand names for Berotralstat?

Berotralstat is marketed under brand names including Orladeyo.

What are the contraindications for Berotralstat?

Berotralstat labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.