Orladeyo (berotralstat)

Taking more than one capsule of Orladeyo a day may cause serious side effects, including:

• heart rhythm problems. A heart rhythm problem called QT prolongation can happen in people who take more than one capsule of Orladeyo a day. This condition can cause an abnormal heart beat. Do not take more than one capsule of Orladeyo a day.

The most common side effects of Orladeyo include:

• abdominal pain
• vomiting
• diarrhea
• back pain
• heartburn

Less common side effects include increases in liver function tests. Rarely, some patients had a brief, itchy rash.

These are not all of the possible side effects of Orladeyo. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Recommended Dosage

• The recommended dosage of Orladeyo is one 150 mg capsule taken orally once daily with food.

Recommended Dosage In Patients With Hepatic Impairment

• No dosage adjustment of Orladeyo is recommended for patients with mild hepatic impairment (Child-Pugh Class A).
• In patients with moderate or severe hepatic impairment (Child-Pugh B or C), the recommended dosage of Orladeyo is one 110 mg capsule taken orally once daily with food.

Recommended Dosage For Concomitant Use With P-Gp Or BCRP Inhibitors

• In patients with chronic administration of P-gp or BCRP inhibitors (e.g., cyclosporine), the recommended dosage of Orladeyo is one 110 mg capsule taken orally once daily with food.

Dosage Adjustment In Patients With Persistent GI Reactions

• Gastrointestinal (GI) reactions may occur in patients receiving Orladeyo. If GI events persist, a reduced dose of 110 mg once daily with food may be considered.

• This section describes clinically relevant drug interactions with Orladeyo. Drug interaction studies are described elsewhere in the labeling.

Potential For Other Drugs To Affect Orladeyo

P-Gp Or BCRP Inhibitors

• Orladeyo is a P-gp and BCRP substrate. A dose of 110 mg Orladeyo is recommended for patients with chronic administration of P-gp or BCRP inhibitors (e.g., cyclosporine).

P-Gp Inducers

• Berotralstat is a substrate of P-gp and BCRP. P-gp inducers (e.g., rifampin, St. John's wort) may decrease berotralstat plasma concentration, leading to reduced efficacy of Orladeyo. The use of P-gp inducers is not recommended with Orladeyo.

Potential For Orladeyo To Affect Other Drugs

CYP2D6 And CYP3A4 Substrates

• Orladeyo at a dose of 150 mg is a moderate inhibitor of CYP2D6 and CYP3A4. For concomitant medications with a narrow therapeutic index that are predominantly metabolized by CYP2D6 (e.g., thioridazine, pimozide) or CYP3A4 (e.g., cyclosporine, fentanyl), appropriate monitoring and dose titration is recommended.

P-Gp Substrates

• Orladeyo at a dose of 300 mg is a P-gp inhibitor. Appropriate monitoring and dose titration is recommended for P-gp substrates (e.g. digoxin) when co-administering with Orladeyo.

• There are insufficient data in pregnant women available to inform drug-related risks with Orladeyo use in pregnancy.
• There are no data on the presence of berotralstat in human milk, its effects on the breastfed infant, or its effects on milk production.
• However, when a drug is present in animal milk, it is likely that the drug will be present in human milk.