Orladeyo for preventing hereditary angioedema attacks in adults and children

Orladeyo (berotralstat) is an oral medication used to prevent hereditary angioedema (HAE) attacks in both adults and children aged 2 years and older. It is not intended for treating acute HAE attacks but for long-term prophylaxis to reduce the frequency of episodes.

Orladeyo is approved to prevent attacks of hereditary angioedema (HAE) in:

• Adults and pediatric patients 12 years of age and older, using capsules.
• Pediatric patients aged 2 to less than 12 years, using oral pellets dosed by body weight.

It should not be used for treating acute HAE attacks.

berotralstat hydrochloride

Orladeyo works by inhibiting plasma kallikrein, an enzyme involved in the production of bradykinin, which causes blood vessels to swell during HAE attacks. By blocking kallikrein, Orladeyo helps reduce the frequency of swelling episodes.

Adults and Pediatric Patients 12 Years and Older

Take 150 mg of Orladeyo capsules orally once daily with food.

Pediatric Patients 2 to Less Than 12 Years of Age (Oral Pellets, by Body Weight)

Hepatic Impairment

• Mild impairment (Child-Pugh Class A): No dosage modification recommended for patients 2 years and older.
• Moderate or severe impairment (Child-Pugh Class B or C): Adults and patients 12 years and older should take 110 mg capsules once daily with food. Use is not recommended in pediatric patients 2 to less than 12 years.

Administration for Oral Pellets

• Do not chew or crush pellets to preserve taste-masking coating.
• Pellets can be swallowed directly with a non-acidic liquid or sprinkled over soft, non-acidic foods (e.g., pudding, mashed potatoes) and consumed immediately.
• A meal should be consumed just before or after dosing.
• Discard pellets if not consumed within 10 minutes after sprinkling on food.

Dosage Adjustments for Gastrointestinal Adverse Reactions

• For persistent GI side effects in patients 12 years and older, consider lowering the dose to 110 mg once daily with food.
• In children 2 to less than 12 years with persistent GI reactions, carefully weigh risks and benefits of continued treatment.

None reported.

QTc Interval Prolongation Risk

Higher-than-recommended doses can increase QTc interval prolongation, which affects heart rhythm. Do not exceed the prescribed once-daily dose or use additional doses for acute HAE attacks.

Not for Acute Attack Treatment

Orladeyo should not be used to treat acute HAE attacks. Its safety and effectiveness in this setting have not been established.

Common Side Effects (≥10%)

• Abdominal pain (including discomfort and tenderness)
• Vomiting
• Diarrhea
• Back pain
• Gastroesophageal reflux disease (acid reflux)

These gastrointestinal side effects tend to occur early, often become less frequent over time, and typically resolve without treatment discontinuation.

Less Common Side Effects (5% to <10%)

• Headache
• Fatigue
• Flatulence (gas)

Rare Side Effects

A maculopapular drug rash was reported in less than 1% of patients; it resolved even when treatment continued.

Laboratory Abnormalities

Elevated liver enzymes (transaminases) were observed rarely. One patient discontinued treatment due to asymptomatic elevated ALT and AST. No serious liver adverse events were reported.