Orladeyo

/ Neopharm (Israel) 1996 Ltd.

The recommended dosage is one 150 mg capsule taken orally once daily with food.
Patients with Hepatic Impairment:
No dosage adjustment 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 is one 110 mg capsule taken orally once daily with food.
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 is one 110 mg capsule taken orally once daily with food.
Patients with Persistent GI Reactions:
Gastrointestinal (GI) reactions may occur in patients receiving this drug. If GI events persist, a reduced dose of 110 mg once daily with food may be considered.

Prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults
and pediatric patients 12 years of age and older.
Limitations of Use:
The safety and effectiveness for the treatment of acute HAE attacks have not been established. This medicinal product should not be used for treatment of acute HAE attacks. Additional doses or doses higher than 150 mg once daily are not recommended due to the potential for QT prolongation.

Hypersensitivity to the active substance or to any of the excipients.

Risk of QT Prolongation with Higher-Than-Recommended Dosages
This medicinal product should not be used for treatment of acute attacks of HAE. Additional doses or doses higher than 150 mg once daily are not recommended. An increase in QT was observed at dosages higher than the recommended 150 mg once daily dosage and was concentration dependent.

Very common: Abdominal Pain, vomiting, diarrhea, back pain, gastroesophageal reflux disease.
Common: Headache, fatigue, flatulence.
See prescribing information for full details.

Potential for Other Drugs to Affect this medicinal profduct:
P-gp or BCRP inhibitors: Berotralstat is a P-gp and BCRP substrate. A dose of 110 mg 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 this drug. The use of P-gp inducers is not recommended with this drug.
Potential for ORLADEYO to Affect Other Drugs:
CYP2D6 and CYP3A4 Substrates: this medicinal product 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: this medicinal product 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 this drug.
See prescribing information for full details.

Pregnancy:
There are insufficient data in pregnant women available to inform drug-related risks 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. 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 2-4% and 15-20%, respectively.
Lactation:
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. Low levels of berotralstat were detected in the plasma of rat pups when dams were dosed with the drug orally during the lactation period. The berotralstat concentration in the pup plasma was approximately 2% of the maternal plasma. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for berotralstat and any potential adverse effects on the breastfed infant from berotralstat or from the underlying maternal condition.
See prescribing information for full details.