REPATHA is indicated: To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults at increased risk for these events. As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in: adults with hypercholesterolemia. adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).
REPATHA is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor indicated: To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults at increased risk for these events. ( 1 ) As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in: adults with hypercholesterolemia.
( 1 ) adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). ( 1 ) adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH). ( 1 )
Contraindications
REPATHA is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in REPATHA. Serious hypersensitivity reactions including angioedema have occurred in patients treated with REPATHA [see Warnings and Precautions (5.1) ] . Patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in REPATHA. ( 4 )
Warnings and precautions
Hypersensitivity Reactions : Angioedema has occurred. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with REPATHA, treat according to the standard of care, and monitor until signs and symptoms resolve. ( 5.1 )
5.1Hypersensitivity Reactions
Hypersensitivity reactions, including angioedema, have been reported in patients treated with REPATHA. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with REPATHA, treat according to the standard of care, and monitor until signs and symptoms resolve. REPATHA is contraindicated in patients with a history of serious hypersensitivity reactions to evolocumab or any excipient in REPATHA [see Contraindications (4) ] .
The prefilled single-dose SureClick ® autoinjector and prefilled single-dose syringe presentations of REPATHA that contain dry natural rubber (a derivative of latex) in the needle cover may cause an allergic reaction in individuals sensitive to latex. Instruct patients to inform their healthcare provider if they are sensitive to latex. Consider prescribing a presentation of REPATHA that does not contain dry natural rubber for individuals that are sensitive to latex [see How Supplied/Storage and Handling (16) ] .
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
Available data from clinical trials and postmarketing reports on REPATHA use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, there were no effects on pregnancy or neonatal/infant development when monkeys were subcutaneously administered evolocumab from organogenesis through parturition at dose exposures up to 12 times the exposure at the maximum recommended human dose of 420 mg every month.
In a similar study with another drug in the PCSK9 inhibitor antibody class, humoral immune suppression was observed in infant monkeys exposed to that drug in utero at all doses. The exposures where immune suppression occurred in infant monkeys were greater than those expected clinically. No assessment for immune suppression was conducted with evolocumab in infant monkeys. Measurable evolocumab serum concentrations were observed in the infant monkeys at birth at comparable levels to maternal serum, indicating that evolocumab, like other IgG antibodies, crosses the placental barrier.
Monoclonal antibodies are transported across the placenta in increasing amounts especially near term; therefore, evolocumab has the potential to be transmitted from the mother to the developing fetus. The estimated background risk of major birth defects and miscarriage for the indicated population(s) 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.
There is a pregnancy safety study for REPATHA. If REPATHA is administered during pregnancy, healthcare providers should report REPATHA exposure by contacting Amgen at 1-800-77-AMGEN (1-800-772-6436) or https://wwwext.amgen.com/products/global-patient-safety/adverse-event-reporting. Data Animal Data In cynomolgus monkeys, no effects on embryo-fetal or postnatal development (up to 6 months of age) were observed when evolocumab was dosed during organogenesis to parturition at 50 mg/kg once every 2 weeks by the subcutaneous route at exposures 30- and 12-fold the recommended human doses of 140 mg every 2 weeks and 420 mg once monthly, respectively, based on plasma AUC.
No test of humoral immunity in infant monkeys was conducted with evolocumab.
Adverse reactions
The following adverse reactions are also discussed in other sections of the label: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Common (> 5% of patients treated with REPATHA and more frequently than placebo) adverse reactions in adults with: Primary hypercholesterolemia: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions. ( 6 ) Established CVD: diabetes mellitus, nasopharyngitis and upper respiratory tract infection.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Medical Information at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in Adults with Primary Hypercholesterolemia The data described below reflect exposure to REPATHA in 8 placebo-controlled trials that included 2651 patients treated with REPATHA, including 557 exposed for 6 months and 515 exposed for 1 year (median treatment duration of 12 weeks) .
The mean age of the population was 57 years, 49% of the population were women, 85% White, 6% Black, 8% Asians, and 2% other races. Adverse Reactions in a 52 - Week Controlled Trial In a 52-week, double-blind, randomized, placebo-controlled trial, 599 patients received 420 mg of REPATHA subcutaneously once monthly [see Clinical Studies (14) ] . The mean age was 56 years (range: 22 to 75 years), 23% were older than 65 years, 52% women, 80% White, 8% Black, 6% Asian; 6% identified as Hispanic ethnicity.
Adverse reactions reported in at least 3% of REPATHA-treated patients, and more frequently than in placebo-treated patients are shown in Table 1. Adverse reactions led to discontinuation of treatment in 2.2% of REPATHA-treated patients and 1% of placebo-treated patients. The most common adverse reaction that led to REPATHA treatment discontinuation and occurred at a rate greater than placebo was myalgia (0.3% versus 0% for REPATHA and placebo, respectively).
Table 1. Adverse Reactions Occurring in ≥ 3% of REPATHA-treated Patients and More Frequently than with Placebo in a 52-Week Trial Placebo (N = 302) % REPATHA (N = 599) % Nasopharyngitis 9.6
10.5 Upper respiratory tract infection 6.3
9.3 Influenza 6.3
7.5 Back pain 5.6
6.2 Injection site reactions includes erythema, pain, bruising 5.0
5.7 Cough 3.6
4.5 Urinary tract infection 3.6
4.5 Sinusitis 3.0
4.2 Headache 3.6
4.0 Myalgia 3.0
4.0 Dizziness 2.6
3.7 Musculoskeletal pain 3.0
3.3 Hypertension 2.3
3.2 Diarrhea 2.6
3.0 Gastroenteritis 2.0
3.0Adverse Reactions in Seven Pooled
12 - Week Controlled Trials In seven pooled 12-week, double-blind, randomized, placebo-controlled trials, 993 patients received 140 mg of REPATHA subcutaneously every 2 weeks and 1059 patients received 420 mg of REPATHA subcutaneously monthly. The mean age was 57 years (range: 18 to 80 years), 29% were older than 65 years, 49% women, 85% White, 5% Black, 9% Asian; 5% identified as Hispanic ethnicity. Adverse reactions reported in at least 1% of REPATHA-treated patients, and more frequently than in placebo-treated patients, are shown in Table 2.
Table 2. Adverse Reactions Occurring in ≥ 1% of REPATHA-treated Patients and More Frequently than with Placebo in Pooled 12-Week Trials Placebo (N = 1224) % REPATHA 140 mg every 2 weeks and 420 mg once monthly combined (N = 2052) % Nasopharyngitis 3.9
4.0 Back pain 2.2
2.3 Upper respiratory tract infection 2.0
2.1 Arthralgia 1.6
1.8 Nausea 1.2
1.8 Fatigue 1.0
1.6 Muscle spasms 1.2
1.3 Urinary tract infection 1.2
1.3 Cough 0.7
1.2 Influenza 1.1
1.2 Contusion 0.5
1.0Adverse Reactions in Eight Pooled Controlled Trials (Seven
12 - Week Trials and One 52 - Week Trial) The adverse reactions described below are from a pool of the 52-week trial and seven 12-week trials. The mean and median exposure durations of REPATHA in this pool of eight trials were 20 weeks and 12 weeks, respectively. Local Injection Site Reactions Injection site reactions occurred in 3.2% and 3.0% of REPATHA-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising.
The proportions of patients who discontinued treatment due to local injection site reactions in REPATHA-treated patients and placebo-treated patients were 0.1% and 0%, respectively. Hypersensitivity Reactions Hypersensitivity reactions occurred in 5.1% and 4.7% of REPATHA-treated and placebo-treated patients, respectively. The most common hypersensitivity reactions were rash (1.0% versus 0.5% for REPATHA and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).
Adverse Reactions in the Cardiovascular Outcomes Trial In a double-blind, randomized, placebo-controlled cardiovascular outcomes trial, 27,525 patients received at least one dose of REPATHA or placebo [see Clinical Studies (14) ] . The mean age was 62.5 years (range: 40 to 86 years), 45% were 65 years or older, 9% were 75 years or older, 25% women, 85% White, 2% Black and 10% Asian; 8% identified as Hispanic ethnicity.
Patients were exposed to REPATHA or placebo for a median of 24.8 months; 91% of patients were exposed for ≥ 12 months, 54% were exposed for ≥ 24 months and 5% were exposed for ≥ 36 months. The safety profile of REPATHA in this trial was generally consistent with the safety profile described above in the 12- and 52-week controlled trials involving patients with primary hypercholesterolemia. Common adverse reactions (> 5% of patients treated with REPATHA and occurring more frequently than placebo) included diabetes mellitus (8.8% REPATHA, 8.2% placebo), nasopharyngitis (7.8% REPATHA, 7.4% placebo), and upper respiratory tract infection (5.1% REPATHA, 4.8% placebo).
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients treated with REPATHA compared with 7.7% in patients that received placebo. Adverse Reactions in Pediatric Patients with HeFH In a 24-week, randomized, placebo-controlled, double-blind trial of 157 pediatric patients with HeFH, 104 patients received 420 mg REPATHA subcutaneously once monthly [see Clinical Studies (14) ] .
The mean age was 13.7 years (range: 10 to 17 years), 56% were female, 85% White, 1% Black, 1% Asian, and 13% other; 8% identified as Hispanic ethnicity. Common adverse reactions (> 5% of patients treated with REPATHA and occurring more frequently than placebo) included: Nasopharyngitis (12% versus 11%) Headache (11% versus 2%) Oropharyngeal pain (7% versus 0%) Influenza (6% versus 4%) Upper respiratory tract infection (6% versus 2%) Adverse Reactions in Adults and Pediatric Patients with HoFH In a 12-week, double-blind, randomized, placebo-controlled trial of 49 patients with HoFH, 33 patients received 420 mg of REPATHA subcutaneously once monthly [see Clinical Studies (14) ] .
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
EVOLOCUMAB 140MG/ML
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application BLA125522.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
The mean age was 31 years (range: 13 to 57 years), 49% were women, 90% White, 4% Asian, and 6% other. The adverse reactions that occurred in at least two (6.1%) REPATHA-treated patients, and more frequently than in placebo-treated patients, included: Upper respiratory tract infection (9.1% versus 6.3%) Influenza (9.1% versus 0%) Gastroenteritis (6.1% versus 0%) Nasopharyngitis (6.1% versus 0%) In a multicenter, open-label 5-year extension study, 106 patients with HoFH, including 14 pediatric patients, received 420 mg of REPATHA subcutaneously once monthly or every 2 weeks [see Clinical Studies (14) ] .
The mean age was 34 years (range: 13 to 68 years), 51% were women, 80% White, 12% Asian, 1% Native American, and 7% other; 5% identified as Hispanic ethnicity. No new adverse reactions were observed during the open-
