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ORLADEYO is a brand name for Berotralstat, supplied as a capsule. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: ORLADEYO (berotralstat) is indicated for the routine prevention of attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years of age and older. Limitations of Use: The safety and efficacy of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations ORLADEYO is not intended for the treatment of acute HAE attacks. Patients should not take additional doses of ORLADEYO to treat an acute attack of HAE. Product Monograph ORLADEYO (berotralstat) 5 BioCryst Pharmaceuticals, Inc.
2 Recommended Dose and Dosage Adjustment Adults and Pediatric Patients (≥12 years and weighing ≥40 kg) The recommended dose of ORLADEYO is one 150 mg capsule, taken orally once daily with food. Geriatrics (≥65 years) No dosage adjustment is required for geriatric patients.
Hepatic Impairment No dosage adjustment is required for patients with mild hepatic impairment. 3 Pharmacokinetics, Special Populations and Conditions, Hepatic Insufficiency). Renal Impairment No dosage adjustment is required for patients with mild or moderate renal impairment.
Use of berotralstat in patients with severe renal impairment should be avoided. 3 Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency). 1 Efficacy and Safety Studies). 5 Missed Dose Advise patients that in the event of a missed dose of ORLADEYO, the missed dose should be taken as soon as possible on the same day, with a return to the normal schedule the following day.
Patients should not take more than one dose per day.
). 1 Adverse Reaction Overview The overall safety of ORLADEYO has been evaluated in multiple long-term clinical studies, which included 381 patients with HAE (uncontrolled, open-label and placebo-controlled, blinded studies). Of the patients treated with ORLADEYO in the placebo-controlled blinded Phase 3 study (Study 302, Part 1), the most common adverse reactions associated with ORLADEYO 150 mg were gastrointestinal reactions, which included abdominal pain in any location (23%), vomiting (15%), Product Monograph ORLADEYO (berotralstat) 8 BioCryst Pharmaceuticals, Inc.
Protected B / Protégé B and diarrhea (15%) (Table 2). These reactions generally occurred early after initiation of treatment with ORLADEYO, became less frequent with time, and typically self-resolved. No patients in the ORLADEYO 150 mg dose group discontinued treatment due to a gastrointestinal adverse reaction.
There were no serious drug-related treatment-emergent adverse events in patients who received ORLADEYO. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials may therefore not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. The primary safety evaluation of ORLADEYO was based on Week 24 data from Part 1 of a 3- part, double-blind, parallel-group, and placebo-controlled study (Study 302) in 120 patients with Type I or II HAE randomized and dosed with either ORLADEYO 110 mg, 150 mg, or placebo, once daily with food.
In Study 302, 81 patients aged 12 years and older with HAE received at least one dose of ORLADEYO in Part 1. The proportion of patients who discontinued study drug prematurely due to adverse reactions was 7% and 3% for patients treated with 110 mg and 150 mg of ORLADEYO, respectively, and 3% for patients treated with placebo.
, Cardiovascular). 1 Pediatrics Pediatrics (≥12 years and weighing ≥40 kg) Based on the data submitted and reviewed by Health Canada, the safety and efficacy of ORLADEYO in pediatric patients in this age and weight group has been established.
Therefore, Health Canada has authorized an indication for pediatric use in patients ≥12 years of age (see 14 CLINICAL TRIALS). The safety and efficacy of ORLADEYO have not been established in patients <12 years of age. 2 Geriatrics (≥65 years) Evidence from clinical studies and experience suggests that use in the geriatric population is not associated with differences in safety or effectiveness (see 14 CLINICAL TRIALS).
Berotralstat has not been studied in patients ≥75 years of age. 2 CONTRAINDICATIONS ORLADEYO is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. 1 Dosing Considerations ORLADEYO is not intended for the treatment of acute HAE attacks. Patients should not take additional doses of ORLADEYO to treat an acute attack of HAE.
Product Monograph ORLADEYO (berotralstat) 5 BioCryst Pharmaceuticals, Inc. 2 Recommended Dose and Dosage Adjustment Adults and Pediatric Patients (≥12 years and weighing ≥40 kg) The recommended dose of ORLADEYO is one 150 mg capsule, taken orally once daily with food.
Geriatrics (≥65 years) No dosage adjustment is required for geriatric patients. Hepatic Impairment No dosage adjustment is required for patients with mild hepatic impairment. 3 Pharmacokinetics, Special Populations and Conditions, Hepatic Insufficiency).
Renal Impairment No dosage adjustment is required for patients with mild or moderate renal impairment. Use of berotralstat in patients with severe renal impairment should be avoided. 3 Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency).
ORLADEYO is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
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Table 2 shows the adverse reactions that occurred in >10% of patients receiving ORLADEYO 150 mg that also occurred at a higher rate (difference of ≥5%) than in the placebo group. Table 2. Adverse Reactions Observed in >10% of Patients Treated with Berotralstat 150 mg or Placebo (Study 302, Part 1, Safety population) Adverse Reaction (MedDRA SOC) Berotralstat 150 mg Placebo (N=40) (N=39) n (%) n (%) Gastrointestinal Disorders: Abdominal paina 9 (23) 4 (10) Vomiting 6 (15) 1 (3) Diarrheab 6 (15) 0 Musculoskeletal and Connective Tissue Disorders: Back Pain 4 (10) 1 (3) Abbreviations: MedDRA = Medical Dictionary for Regulatory Activities, SOC = System Organ Class a Includes abdominal pain, abdominal discomfort, and abdominal tenderness.
b Includes diarrhea and frequent bowel movements. Product Monograph ORLADEYO (berotralstat) 9 BioCryst Pharmaceuticals, Inc. 1 Clinical Trial Adverse Reactions – Pediatrics The safety of ORLADEYO was evaluated in a subgroup of 6 pediatric patients aged 12 to <18 years and weighing ≥40 kg as part of Study 302, and in 28 pediatric patients aged 12 to <18 years as part of Study 204, the long-term, open-label safety study.
The safety profile was similar to that observed in adults. Adverse reactions applicable to adults are also applicable to pediatric use. 3 Less Common Clinical Trial Adverse Reactions Less frequent adverse reactions that occurred with an incidence <10% included: Gastrointestinal Disorders: Flatulence, gastroesophageal reflux disease Nervous System Disorders: Headache Skin and Subcutaneous Tissue Disorders: Rash A maculopapular drug rash was reported in <1% of patients treated with ORLADEYO.
The rash resolved, including in patients who continued dosing. 4 Abnormal Laboratory Findings: Hematology, Clinical Chemistry and Other Quantitative Data Table 3 shows treatment-emergent laboratory abnormalities that occurred in patients receiving ORLADEYO 150 mg that also occurred at a higher rate than in the placebo group.
Table 3. 0) 0 Product Monograph ORLADEYO (berotralstat) 10 BioCryst Pharmaceuticals, Inc.
Protected B / Protégé B Abbreviations:
ALT = Alanine Aminotransferase, AST = Aspartate Aminotransferase, GGT = Gamma Glutamyl Transferase a Grade determined by DMID (Division of Microbiology and Infectious Diseases) Adult Toxicity Table (November 2007). b The same subject had elevations in ALT (Grade 3 and 4), AST (Grade 3 and ≥2 Grade Shift) and GGT (Grade 3 and ≥2 Grade Shift) which were reported as a treatment-emergent adverse event (LFT abnormal).
c The same subject had elevations in Amylase (Grade 3) and Lipase (Grade 3). No treatment-emergent adverse event was reported related to these findings. LFT elevations, which generally improved with or without discontinuation of berotralstat, were observed in some patients, primarily in those who discontinued androgen therapy within 14 days of initiating ORLADEYO treatment in Study 204, the long-term, open-label safety study.
Abrupt discontinuation of androgens immediately prior to initiating ORLADEYO should be avoided. 5 Post-Market Adverse Reactions The following adverse reactions have been identified during post-market use of ORLADEYO. Because post-market reactions are reported […]
1 Efficacy and Safety Studies). 5 Missed Dose Advise patients that in the event of a missed dose of ORLADEYO, the missed dose should be taken as soon as possible on the same day, with a return to the normal schedule the following day.
Patients should not take more than one dose per day. 5 OVERDOSAGE There is no experience with overdoses of ORLADEYO. There is no available information to identify potential signs and symptoms of overdose. In clinical trials, the highest single dose taken was 890 mg and the highest daily dose was 450 mg for 14 days.
No serious adverse reactions were reported with these higher doses. For management of a suspected drug overdose, contact your regional poison control centre. Product Monograph ORLADEYO (berotralstat) 6 BioCryst Pharmaceuticals, Inc. Protected B / Protégé B 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 1.
Dosage Forms, Strengths, Composition and Packaging Route of Administration Dosage Form / Strength / Composition Non-medicinal Ingredients Oral Capsule 150 mg berotralstat (as berotralstat hydrochloride) Black iron oxide, colloidal silicon dioxide, crospovidone, gelatin, indigo carmine (FD&C Blue #2), magnesium stearate, pharmaceutical grade printing ink, pregelatinized starch, red iron oxide, titanium dioxide ORLADEYO comes in size 1 capsules with a light blue opaque cap, with black imprint “BCX” and a white opaque body with black imprint “150”.
ORLADEYO capsules are available in a rigid film blister card with an aluminum foil backing. A 28-day supply is provided in a carton containing four 7-capsule blister cards. 7 WARNINGS AND PRECAUTIONS General ORLADEYO should not be used for treatment of acute attacks of HAE.
In the event of an acute attack, individualized treatment should be initiated with an approved rescue medicine. Cardiovascular Additional doses or doses of ORLADEYO higher than 150 mg once daily are not recommended. 2 Pharmacodynamics).
Educate patients on the importance of treatment compliance. Hepatic/Biliary/Pancreatic Patients with moderate or severe hepatic impairment may develop increased serum berotralstat concentrations. 3 Pharmacokinetics, Special Populations and Conditions, Hepatic Insufficiency).
Reproductive Health:
Female and Male Potential Fertility There are no data on the influence of berotralstat use on human fertility. Based on animal studies, no effect on reproduction or fertility is expected with berotralstat (see 16 NON- CLINICAL TOXICOLOGY).
Product Monograph ORLADEYO (berotralstat) 7 BioCryst Pharmaceuticals, Inc. 1 Pregnant Women There are insufficient data in pregnant women available to inform drug-related risks with ORLADEYO use in pregnancy. Animal studies did not indicate any direct or indirect harmful effects with respect to reproductive toxicity (see 16 NON-CLINICAL TOXICOLOGY).
As a precautionary measure, it is preferable to avoid the use of ORLADEYO during pregnancy. 2 Breast-feeding There are no data on the presence of berotralstat in human milk. A study conducted in rats demonstrated that the Cmax of berotralstat in pup plasma on Lactation Day 14 was <5% of the maternal plasma Cmax.
3 Pharmacokinetics, 16 NON-CLINICAL TOXICOLOGY). A risk to the newborns/infants cannot […]