What Is Orladeyo Capsule Used For?

Gastrointestinal (GI) reactions may occur in patients receiving ORLADEYO [see Adverse Reactions (6.1)].

1. For adults and pediatric patients 12 years of age and older, if GI adverse reactions persist, consider a lower ORLADEYO capsules dosage of 110 mg once daily with food.
2. For pediatric patients 2 to less than 12 years of age with persistent GI adverse reactions, consider the risks and benefits of continuing treatment with ORLADEYO.

The following clinically significant adverse reaction is described elsewhere in the labeling:

1. QTc Interval Prolongation [see Warnings and Precautions (5.1)].

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)].

• 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)]. Table 1: Recommended Dosage of ORLADEYO Oral Pellets by Body Weight in Pediatric Patients 2 Years to Less than 12 Years of Age Body Weight (kg) Recommended Dosage of ORLADEYO Oral Pellets 12 kg to less than 24 kg 72 mg (one packet) once daily 24 kg to less than 32 kg 96 mg (one packet) once daily 32 kg to less than 40 kg 108 mg (one packet) once daily 40 kg or greater 132 mg (one packet) once daily 2.3 Recommended Dosage in Patients with Hepatic Impairment Mild Hepatic Impairment (Child-Pugh Class A) Adult and Pediatric Patients 2 Years of Age and Older • No dosage modification of ORLADEYO is recommended [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Moderate or Severe Hepatic Impairment (Child-Pugh Class B or C) Adult and Pediatric Patients 12 Years of Age and Older • Recommended dosage of ORLADEYO capsules is 110 mg taken orally once daily with food [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Pediatric Patients 2 Years to Less than 12 Years of Age • Avoid use of ORLADEYO [see Use in Specific Populations (8.7)]. 2.4 Dosage Modification in Patients with Persistent GI Adverse Reactions Gastrointestinal (GI) reactions may occur in patients receiving ORLADEYO [see Adverse Reactions (6.1)]. • For adults and pediatric patients 12 years of age and older, if GI adverse reactions persist, consider a lower ORLADEYO capsules dosage of 110 mg once daily with food. • For pediatric patients 2 to less than 12 years of age with persistent GI adverse reactions, consider the risks and benefits of continuing treatment with ORLADEYO. 2.5 Administration Instructions for Oral Pellets Do not chew or crush ORLADEYO oral pellets because this will affect the film coating (taste masking) and result in bitter taste. Administer one packet of oral pellets as follows: • Pour the entire contents of one packet directly into the mouth and swallow immediately with non-acidic liquid (e.g., water or milk). OR • Sprinkle the entire contents of one packet over approximately one tablespoon (15 mL) of soft, non-acidic food and consume immediately. Food should be at or below room temperature. Examples of soft, non-acidic foods include pudding, mashed potatoes, creamed corn, pureed peas, pureed bananas, and pureed carrots. Acidic foods such as yogurt and applesauce should not be used because they can dissolve the film coating (taste masking) and result in a bitter taste. The film coating (taste masking) remains intact for 10 minutes. If the pellets are not consumed within 10 minutes of sprinkling over food, they should be discarded.

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.

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)].

Mild Hepatic Impairment (Child-Pugh Class A) Adult and Pediatric Patients 2 Years of Age and Older • No dosage modification of ORLADEYO is recommended [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Moderate or Severe Hepatic Impairment (Child-Pugh Class B or C) Adult and Pediatric Patients 12 Years of Age and Older • Recommended dosage of ORLADEYO capsules is 110 mg taken orally once daily with food [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Pediatric Patients 2 Years to Less than 12 Years of Age • Avoid use of ORLADEYO [see Use in Specific Populations (8.7)].

Gastrointestinal (GI) reactions may occur in patients receiving ORLADEYO [see Adverse Reactions (6.1)].

1. For adults and pediatric patients 12 years of age and older, if GI adverse reactions persist, consider a lower ORLADEYO capsules dosage of 110 mg once daily with food.
2. For pediatric patients 2 to less than 12 years of age with persistent GI adverse reactions, consider the risks and benefits of continuing treatment with ORLADEYO.

• Capsules: 150 mg, 110 mg (3) • Oral Pellets: 72 mg, 96 mg, 108 mg, or 132 mg in unit-dose packets (3) Capsules: • 150 mg: a white opaque body with a black imprint "150" and a light blue opaque cap with a black imprint "BCX". • 110 mg: light blue opaque body and cap with a white imprint "110" on body and a white imprint "BCX" on cap. Oral Pellets: • 72 mg, 96 mg, 108 mg, or 132 mg, white to off-white film-coated pellets in unit-dose packets.

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)].

• P-gp inducers: Avoid use with ORLADEYO. (7.1)

• CYP2D6, CYP3A4 or P-gp Substrates: When used concomitantly with ORLADEYO, closely monitor or modify the dosage of the substrates where minimal increases in concentration may lead to serious adverse reactions. (7.2, 12.3) 7.1 Effect of Other Drugs on ORLADEYO

P-gp Inducers

Berotralstat is a substrate of P-gp and BCRP. P-gp inducers may decrease berotralstat plasma concentration, leading to reduced efficacy of ORLADEYO. Avoid concomitant use of P-gp inducers with ORLADEYO. 7.2 Effect of ORLADEYO on Other Drugs

CYP2D6 and CYP3A4 Substrates

ORLADEYO at a dose of 150 mg is a moderate inhibitor of CYP2D6 and CYP3A4. Concomitant use of ORLADEYO with CYP2D6 or CYP3A4 substrates can increase exposure of the CYP2D6 or CYP3A4 substrates and may increase the risk of adverse reactions associated with the substrates. If ORLADEYO is concomitantly used with CYP2D6 or CYP3A4 substrates where minimal increases in the concentration of the substrates may lead to serious adverse reactions, closely monitor or modify the dosage of the CYP2D6 or CYP3A4 substrate [see Clinical Pharmacology (12.3)]. Refer to the Prescribing Information of the CYP2D6 or CYP3A4 substrate. Desogestrel

Concomitant use of ORLADEYO with desogestrel increases exposure to etonogestrel, the active metabolite of desogestrel, and may increase the risk of desogestrel-associated adverse reactions. Consider the benefits and risks when using ORLADEYO concomitantly with desogestrel [see Clinical Pharmacology (12.3)]. P-gp Substrates

ORLADEYO at 2-times the maximum recommended dose of 150 mg is a P-gp inhibitor and can increase exposure of P-gp substrates, leading to increased risk of adverse reactions associated with the substrates. Higher-than-recommended dosages of ORLADEYO are not recommended [see Warnings and Precautions (5.1)]. If ORLADEYO is concomitantly used with P-gp substrates where minimal increases in the concentration of the substrates may lead to serious adverse reactions, closely monitor or modify the dosage of the P-gp substrate [see Clinical Pharmacology (12.3)]. Refer to the Prescribing Information of the P-gp substrate.