Berotralstat

Berotralstat (Orladeyo) is a prescription medicine used to reduce the frequency of hereditary angioedema (HAE) attacks in adults and children 2 years and older. It works by inhibiting plasma kallikrein, an enzyme that contributes to excessive bradykinin production, which leads to swelling and inflammation in HAE. It is not used to treat acute HAE attacks.

Berotralstat is taken once daily with food. Its brand name is Orladeyo, made by BioCryst Pharmaceuticals, Inc.

Berotralstat was FDA approved for the prevention of recurrent HAE attacks on December 3, 2020, after positive results from Trial 1 (NCT03485911). Over 24 weeks, patients taking berotralstat had a:

• 30% reduction in HAE attack rate on 110 mg daily
• 44.2% reduction in HAE attack rate on 150 mg daily

How does berotralstat work?

In hereditary angioedema, excessive kallikrein activity results in high levels of bradykinin, causing blood vessel leakage and swelling. Berotralstat is a plasma kallikrein inhibitor that binds to plasma kallikrein, reducing its activity and helping to prevent angioedema attacks.

• QT prolongation risk: do not take more than your prescribed dose, and do not exceed 150 mg per day.

Before taking berotralstat for HAE, tell your doctor if you have ever had:

• Liver or kidney disease
• Heart rhythm problems

Berotralstat is not approved for children under 2 years of age.

Pregnancy

Tell your healthcare professional if you are pregnant or planning to become pregnant, as it is not known whether berotralstat can harm your unborn baby.

Breastfeeding

Tell your healthcare professional if you are breastfeeding or planning to breastfeed, as it is not known whether berotralstat passes into breast milk. Talk to your healthcare professional about the best way to feed your baby.

Common berotralstat side effects

Common side effects of berotralstat include:

• Abdominal pain (16%)
• Vomiting (12%)
• Diarrhea (12%)
• Heartburn (7%)
• Back pain (6%)

These common side effects occurred in patients taking berotralstat 110 mg or 150 mg once daily in 24-week (Part 1) data from a 3-part, double-blind, parallel-group, placebo-controlled clinical trial (Trial 1, NCT03485911).

Less common side effects include increases in liver function (liver enzyme) tests. Rarely, some people had a brief, itchy skin rash, which went away even in people who kept taking the medicine.

Serious side effects

QT prolongation (irregular heart rhythm) may occur if more than one dose is taken per day. Take only one dose a day and do not take an extra dose.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Adults and children 12 years and older: one 150 mg capsule once daily with food. A 150 mg oral pellet packet once daily with food is also available for this age group, for example for people who have trouble swallowing capsules.

Children 2 to under 12 years: oral pellets are taken once daily, with the dose based on body weight. Your healthcare provider will calculate the dose. Do not chew or crush the oral pellets. Pour the pellets directly into the mouth and swallow right away with a non-acidic liquid (such as water or milk), or sprinkle them over 1 tablespoon of soft, non-acidic food and consume immediately. Do not sprinkle on acidic foods like yogurt or applesauce.

• Dose adjustments may be needed for patients with moderate or severe liver impairment (110 mg capsule once daily) or with persistent gastrointestinal (GI) reactions.
• Do not take more than one dose per day, as it may lead to serious heart rhythm problems (QT prolongation).

What happens if I miss a dose?

• Take it as soon as you remember.
• Skip the missed dose if it is almost time for your next dose.
• Do not double up on doses.

What happens if I overdose?

• Call the Poison Help line (1-800-222-1222) or seek emergency medical attention immediately.

Berotralstat may interact with other medications, including:

• P-gp inducers: avoid use with berotralstat.
• CYP2D6, CYP3A4, or P-gp substrates: monitor closely or adjust the dose of narrow therapeutic index medicines that are mainly metabolized by CYP2D6 or CYP3A4, or that are P-gp substrates, when taken with berotralstat.
• Desogestrel: taking berotralstat with desogestrel may increase the risk of side effects associated with desogestrel. Discuss the benefits and risks with your doctor.

Tell your doctor about all medications, vitamins, and supplements you take. Not all possible interactions are listed here.

HCPs and patients often use the Berotralstat Package Insert (Orladeyo) for more detailed information about this medicine. The Package Insert (PI) contains more comprehensive information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interactions, and more. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment. The Package Insert is sometimes called the Berotralstat Prescribing Information or FDA label.

• Store at room temperature, 68°F to 77°F (20°C to 25°C). Short periods between 59°F and 86°F (15°C and 30°C) are OK.
• Each carton has a tamper-evident seal. Do not use berotralstat if the seal is broken or missing.
• Keep out of reach of children.

Active ingredient: berotralstat dihydrochloride

Inactive ingredients: colloidal silicon dioxide, crospovidone, magnesium stearate, and pregelatinized starch. The oral pellets film-coating contains butylated methacrylate copolymer, silicon dioxide, sodium lauryl sulphate, stearic acid, talc, and titanium dioxide.

BioCryst Pharmaceuticals, Inc., Durham, NC 27703.