Orladeyo
Orladeyo Uses, Dosage, Side Effects, Food Interaction and all others data.
Orladeyo is a selective inhibitor of plasma kallikrein used in the prophylaxis of attacks of hereditary angioedema (HAE). It works by blocking the enzymatic activity of plasma kallikrein in releasing bradykinin, the major biologic peptide that promotes swelling and pain associated with attacks of HAE. Developed by BioCryst Pharmaceuticals, berotralstat is taken once-daily as oral capsules. Under the market name Orladeyo, berotralstat was approved by the FDA on December 3, 2020, as the first oral, once-daily therapy to prevent angioedema attacks of HAE in adults and pediatric patients 12 years and older. In clinical trials, berotralstat was shown to significantly reduce attack rates at 24 weeks compared to placebo, which was sustained through 48 weeks. Orladeyo is strictly used to prevent, but not treat, these attacks. Previous oral therapies used for prophylaxis of HAE attacks, such as androgens, were limited by undesirable adverse effects and several contraindications. In clinical trials, berotralstat displayed a fast onset of action, long duration of action, and acceptable tolerance in patients.
Orladeyo prevents angioedema attacks by inhibiting plasma kallikrein, thereby regulating excess bradykinin generation in patients with hereditary angioedema. It has a fast onset of action, long duration of action, and acceptable tolerance. Orladeyo inhibits plasma kallikrein in a concentration-dependent. In clinical trials, doses of berotralstat higher than 150 mg once daily led to QT Prolongation in a concentration-dependent manner.
| Trade Name | Orladeyo |
| Availability | Prescription only |
| Generic | Berotralstat |
| Berotralstat Other Names | Berotralstat |
| Related Drugs | Firazyr, Haegarda, Ruconest, Berinert, Cinryze, Kalbitor |
| Weight | 110mg, 150mg, |
| Type | Oral capsule |
| Formula | C30H26F4N6O |
| Weight | Average: 562.573 Monoisotopic: 562.210422133 |
| Protein binding | Plasma protein binding is approximately 99%. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Orladeyo is an inhibitor of plasma kallikrein used for prophylaxis of angioedema attacks in patients with hereditary angioedema.
Orladeyo is indicated for prophylaxis of attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older. It is not used for the treatment of acute HAE attacks.
Orladeyo is also used to associated treatment for these conditions: Acute attack of hereditary angioedema
How Orladeyo works
Hereditary angioedema (HAE) is a rare genetic disorder associated with severe swelling of the skin and upper airway. It is caused by mutations in the regulatory or coding regions of the gene that encodes C1 inhibitor (SERPING1), which result in either a deficiency (type I) or dysfunction (type II) of C1 inhibitor (C1 esterase inhibitor, C1-INH). C1 inhibitor is a serine protease inhibitor that normally regulates bradykinin production by covalently binding to and inactivating plasma kallikrein.
Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK (cHMWK). During HAE attacks, the levels of plasma kallikrein fall, leading to the cleavage of high-molecular-weight-kininogen and the release of bradykinin, a potent vasodilator that increases vascular permeability. Bradykinin plays a major role in promoting edema and pain associated with HAE. Patients with HAE cannot properly regulate plasma kallikrein activity due to the deficiency or dysfunction of a serum inhibitor of C1 inhibitor, leading to uncontrolled increases in plasma kallikrein activity and recurrent angioedema attacks. Orladeyo is a potent inhibitor of plasma kallikrein that works by binding to plasma kallikrein and blocking its proteolytic activity, thereby controlling excess bradykinin generation.
Toxicity
There is no information on the LD50 or overdose of berotralstat.
Food Interaction
- Take with food. This is instructed by the prescribing information of berotralstat. A high-fat meal had no significant effects on the Cmax and AUC of berotralstat, but the Tmax was delayed by 3 hours.
Orladeyo Disease Interaction
Volume of Distribution
The blood to plasma ratio was approximately 0.92 following a single 300 mg dose administration of radiolabeled berotralstat.
Elimination Route
The steady-state of berotralstat is reached within 6 to 12 days following initial administration. After once-daily administration, the Cmax and AUC of berotralstat at steady-state is approximately five times that of the drug after a single dose. Following oral administration of berotralstat once-daily, the steady-state Cmax was 158 ng/mL (range: 110 to 234 ng/mL) at the dose of 150 mg and 97.8 ng/mL (range: 63 to 235 ng/mL) at the dose of 110 mg. The area under the curve over the dosing interval (AUCtau) was 2770 nghr/mL (range: 1880 to 3790 nghr/mL) and 1600 nghr/mL (range: 950 to 4170 nghr/mL) at the dose of 110 mg. The median Tmax is 2 hours in a fasted state and a high-fat meal delays the Tmax to 5 hours. The Tmax can range from 1 to 8 hours.
Half Life
Following a single oral dose administration of 300 mg radiolabeled berotralstat, the median elimination half-life of berotralstat was approximately 93 hours, ranging from 39 to 152 hours.
Clearance
There is no information on the clearance rate.
Elimination Route
Following a single oral dose administration of 300 mg radiolabeled berotralstat, approximately 9% of the drug was excreted in the urine, where 1.8 to 4.7% of the total radiolabeled compound accounted for the unchanged parent drug. About 79% of the drug was excreted in feces.
Innovators Monograph
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