Pronunciation: or-luh-DAY-oh
Generic name: berotralstat [ BER-oh-TRAL-stat ]
Dosage form: capsules (150 mg, 110 mg)
Drug class: Hereditary angioedema agents
What is Orladeyo?
Orladeyo capsules are used to prevent attacks of hereditary angioedema (HAE), in adults and children aged 12 years and older. Orladeyo works by blocking plasma kallikrein, an enzyme that leads to the production of bradykinin, a substance that causes swelling and pain in hereditary angioedema.
Orladeyo is a once-daily capsule used as a preventative treatment for hereditary angioedema.
Hereditary angioedema is a rare and potentially life-threatening genetic disorder that causes an attack of rapid swelling in the face, throat, arms, legs, or around the abdomen.
Orladeyo FDA approval was granted to BioCryst Pharmaceuticals, Inc., on December 3, 2020. Orladeyo FDA approval is for the prevention of hereditary angioedema (HAE) attacks in adults and pediatric patients 12 years and older.
Orladeyo is not used for treating a hereditary angioedema attack that has already begun.
How does Orladeyo work?
In hereditary angioedema, a C1 esterase deficiency leads to the overactivation of plasma kallikrein, which causes high levels of bradykinin, a protein that causes blood vessels to widen and leak, and results in swelling and pain of angioedema attacks.
Orladeyo mechanism of action is by binding to plasma kallikrein which controls excess bradykinin generation, reducing the risk of angioedema attacks
Orladeyo (berotralstat) is from a class of medicines called kallikrein inhibitors.
How well does Orladeyo work?
Orladeyo was shown to be effective in treating hereditary angioedema, with positive results from a 48-week Clinical trial APeX-2 (NCT03485911), which demonstrated that Orladeyo patients had a:
- 67% reduction in hereditary angioedema attack rate using 150mg daily
- 52% reduction in hereditary angioedema attack rate using 110mg daily
Orladeyo side effects
Common Orladeyo side effects
Common Orladeyo side effects may include:
- Stomach pain (10%)
- Indigestion (10%)
- Vomiting (10%)
- Diarrhea (10%)
- Back pain (2%)
These common side effects occurred in 10% or more of Orladeyo patients taking 110mg in the 24-week (Part 1) clinical trial called Trial 1. Gastrointestinal side effects including abdominal pain, vomiting, and diarrhea occurred more frequently in patients receiving Orladeyo 150 mg. These side effects usually occurred when first starting treatment and became less frequent over time.
Serious side effects
Allergic reaction. Get emergency medical help if you have signs of an allergic reaction to this medicine with symptoms of hives; difficulty breathing; and swelling of your face, lips, tongue, or throat.
QT prolongation. Taking more than one capsule a day may cause serious side effects of heart rhythm problems. QT prolongation is a heart rhythm problem that can happen in people who take more than one capsule a day. This condition can cause an abnormal heartbeat. Do not take more than one capsule a day.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.
Warnings
QT Prolongation Risk: An increase in QT prolongation can occur at dosages higher than the recommended 150 mg once daily dosage. Do not exceed 150 mg per day.
Before taking this medicine
Before taking Orladeyo for HAE make sure this medicine is safe for you, tell your doctor if you have ever had:
- Liver disease
- Kidney Disease (or if you are on dialysis)
- Heart rhythm problems.
Orladeyo is not approved for use by anyone younger than 12 years old.
Pregnancy
Tell your healthcare professional if you are pregnant or planning to become pregnant as it is not known if Orladeyo can harm your unborn baby.
Breastfeeding
Tell your healthcare professional if you are breastfeeding or planning to breastfeed as it is not known if Orladeyo passes into breast milk. Talk to your healthcare professional about the best way to feed your baby.
Orladeyo Dosing Information
Recommended Orladeyo dosage: One capsule (150 mg) taken orally once daily with food.
Dose adjustment for ongoing GI reactions: Gastrointestinal side effects can occur in some patients. If these side effects persist a reduce dose of 110mg once daily with food may be considered.
Dose adjustment for hepatic impairment:
- No adjustment is required for mild hepatic impairment (Child-Pugh Class A)
- For Patients with moderate or severe hepatic impairment (Child-Pugh B or C) the recommended dose is one 110 mg capsule taken orally once daily with food
What happens if I miss a dose?
- Take 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 other drugs will affect this medicine?
Orladeyo may interact with other medications, including:
- P-gp inducers – avoid use with Orladeyo.
- CYP2D6, CYP3A4, or P-gp substrates – monitor closely or dose titrate narrow therapeutic index medications that are predominantly metabolized by CYP2D6, CYP3A4 or are P-gp substrates when co-administered with Orladeyo.
