
Drug Safety-related Labeling Changes (SrLC) Database
ANDA | Abbreviated New Drug Application |
BLA | Biologics License Application |
CDER | Center for Drug Evaluation and Research |
MG | Medication Guide |
NDA | New Drug Application |
PCI | Patient Counseling Information |
PI | Patient Information |
PLR | Physician Labeling Rule |
PLLR | Pregnancy and Lactation Labeling Rule |
Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
BW | Box Warning |
WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
REPATHA (BLA-125522)
(EVOLOCUMAB)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
11/20/2024 (SUPPL-44)
5 Warnings and Precautions
Additions and/or revisions underlined:
…
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)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions and/or revisions underlined:
What is REPATHA?
REPATHA is an injectable prescription medicine used:
To reduce the risk of major adverse cardiovascular (CV) events, such as death from cardiovascular disease, heart attack, stroke, certain types of chest pain conditions (unstable angina) requiring hospitalization, or certain types of heart surgery, in adults with cardiovascular disease.
…
What should I tell my healthcare provider before using REPATHA?
Before you or your child start using REPATHA, tell your healthcare provider about all your medical conditions, including if you or your child:
are allergic to rubber or latex. REPATHA is available as prefilled single-dose SureClick® autoinjectors and prefilled single-dose syringes that either contain dry natural rubber (a derivative of latex) in the needle cover or are not made with natural rubber latex. The carton and “Instructions for Use” will state if your prefilled single-dose SureClick autoinjector or prefilled single-dose syringe contains dry natural rubber.
…
How should I use REPATHA?
…
If your healthcare provider decides that you or your child or a caregiver can give REPATHA, you or your child or your caregiver should receive training on the right way to prepare and inject REPATHA. Do not try to inject REPATHA until you or your child have been shown the right way by your healthcare provider or nurse.
If you or your child are using the prefilled single-dose SureClick autoinjector, put the yellow safety guard (needle inside) of the prefilled single-dose SureClick autoinjector on the skin before injecting.
You or your child can inject into the thigh, upper arm, or stomach (abdomen), except for a two-inch area around the belly button.
Do not choose an area where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.
Always check the label of your prefilled single-dose SureClick autoinjector, prefilled single-dose syringe, or single-dose on-body infusor with prefilled cartridge to make sure you have the correct medicine and the correct dose of REPATHA before each injection.
…
How should I store REPATHA?
Store REPATHA in the refrigerator between 36°F to 46°F (2°C to 8°C). Store REPATHA in the original carton until use to protect it from light.
If needed, REPATHA can be stored at room temperature between 68°F to 77°F (20°C to 25°C) in the original carton for up to 30 days. Throw away REPATHA that has been stored at room temperature for more than 30 days.
Do not freeze REPATHA.
Do not shake REPATHA.
Keep REPATHA and all medicines out of the reach of children.
…
What are the ingredients in REPATHA?
Active Ingredient: evolocumab
Inactive Ingredients: proline; acetate; polysorbate 80; water for injection, USP; and sodium hydroxide.
Additions and/or revisions underlined:
…
Latex-Sensitivity
Instruct patients to inform their healthcare provider if they are sensitive to latex. Inform patients that REPATHA is available as prefilled single-dose SureClick® autoinjectors and prefilled single-dose syringes that either contain dry natural rubber (a derivative of latex) in the needle cover or are not made with natural rubber latex, and the carton and Instructions for Use state if the product contains dry natural rubber. Advise latex-sensitive patients that the needle cover of the glass prefilled single-dose SureClick® autoinjector and prefilled single-dose syringe that contain dry natural rubber (a derivative of latex) may cause allergic reactions in individuals sensitive to latex. [see How Supplied/Storage and Handling (16)].
Pregnancy
Advise women who are exposed to REPATHA during pregnancy that there is a pregnancy safety study that monitors pregnancy outcomes. Encourage these patients to report their pregnancy to Amgen at
1-800-77-AMGEN (1-800-772-6436) or https://wwwext.amgen.com/products/global-patient- safety/adverse-event-reporting [see Use in Specific Populations (8.1)].
Administration
Provide guidance to patients and caregivers on proper subcutaneous administration technique and how to use the prefilled single-dose SureClick® autoinjector, prefilled single-dose syringe, or single-dose
on-body infusor with prefilled cartridge correctly. Inform patients that it may take up to 15 seconds to administer REPATHA using the prefilled single-dose SureClick® autoinjector or prefilled single-dose syringe and about 5 minutes to administer REPATHA using the single-dose on-body infusor with prefilled cartridge.
…
09/24/2021 (SUPPL-29)
6 Adverse Reactions
6.1 Clinical Trials Experience(Additions and/or revisions underlined)
…
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)]. 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%)
…
(Additions and/or revisions underlined)
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to REPATHA in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
The immunogenicity of REPATHA has been evaluated using an electrochemiluminescent bridging screening immunoassay for the detection of binding anti-drug antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralizing antibodies.
In a pool of placebo- and active-controlled clinical trials, 0.3% (48 out of 17,992) of adult patients treated with at least one dose of REPATHA tested positive for the development of binding antibodies. Patients whose sera tested positive for binding antibodies were further evaluated for neutralizing antibodies; none of the patients tested positive for neutralizing antibodies.
The development of anti-evolocumab antibodies was not detected in clinical trials of pediatric patients treated with REPATHA.
There was no evidence that the presence of anti-drug binding antibodies impacted the pharmacokinetic profile, clinical response, or safety of REPATHA.
8 Use in Specific Populations
8.1 Pregnancy(Additions and/or revisions underlined)
…
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.
…
(Additions and/or revisions underlined)
The safety and effectiveness of REPATHA in combination with diet and other LDL-C-lowering therapies for the treatment of HoFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is supported by evidence from an adequate and well-controlled trial in adults and pediatric patients aged 13 years and older with HoFH (including 7 pediatric patients treated with REPATHA) and from open-label studies which included an additional 19 pediatric patients aged 11 years and older with HoFH not previously treated with REPATHA [see Adverse Reactions (6.1) and Clinical Studies (14)].
The safety and effectiveness of REPATHA as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HeFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is based on data from a 24-week, randomized, placebo-controlled,
double-blind trial in pediatric patients with HeFH. In the trial, 104 patients received REPATHA 420 mg subcutaneously once monthly and 53 patients received placebo; 39 patients (25%) were 10 to 11 years of age [see Adverse Reactions (6.1) and Clinical Studies (14)].
The safety and effectiveness of REPATHA have not been established in pediatric patients with HeFH or HoFH who are younger than 10 years old or in pediatric patients with other types of hyperlipidemia.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(Additions and/or revisions underlined)
…
Pregnancy
Advise women who are exposed to REPATHA during pregnancy that there is a pregnancy safety study that monitors pregnancy outcomes. Encourage these patients to report their pregnancy to Amgen at
1-800-77-AMGEN (1-800-772-6436) or https://wwwext.amgen.com/products/global-patient- safety/adverse-event-reporting [see Use in Specific Populations (8.1)].
…
(Extensive revisions; please refer to label)
02/15/2019 (SUPPL-22)
6 Adverse Reactions
6.3 Postmarketing Experience(Additions and/or revisions are underlined)
The following additional adverse reactions have been identified during post-approval use of REPATHA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Influenza-like illness
10/18/2018 (SUPPL-17)
4 Contraindications
(Additions and/or revisions are underlined)
REPATHA is contraindicated in patients with a history of a serious hypersensitivity reaction to REPATHA. Serious hypersensitivity reactions including angioedema have occurrred in patients treated with REPATHA.
5 Warnings and Precautions
5.1 Allergic Reactions(Additions and/or revisions are underlined)
Hypersensitivity reactions (e.g., angioedema, rash, urticaria) have been reported in patients treated with REPATHA, including some that led to discontinuation of therapy. If signs or symptoms of serious allergic reactions occur, discontinue treatment with REPATHA, treat according to the standard of care, and monitor until signs and symptoms resolve.
6 Adverse Reactions
6.3 Postmarketing Experience(Additions and/or revisions are underlined)
The following additional adverse reactions have been identified during postapproval use of REPATHA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Allergic reactions: Angioedema
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
Inform patients that serious hypersensitivity reactions (e.g., angioedema) have been reported in patients treated with REPATHA. Advise patients on the symptoms of hypersensitivity reactions and instruct them to discontinue REPATHA and seek medical attention promptly, if such symptoms occur.
12/01/2017 (SUPPL-13)
6 Adverse Reactions
6.1 Clinical Trials Experience(Additions and/or revisions are underlined)
Adverse Reactions in Adults with Primary Hyperlipidemia (including Heterozygous Familial Hypercholesterolemia)
…
Adverse Reactions in a 52-Week Controlled Trial
In a 52-week, double-blind, randomized, placebo-controlled trial (Study 3 [DESCARTES, NCT01516879]), 599 patients received 420 mg of REPATHA subcutaneously once monthly. 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 in DESCARTES, are shown in Table 1…
Table 1. Adverse Reactions Occurring in Greater than or Equal to 3% of REPATHA-treated Patients and More Frequently than with Placebo in DESCARTES
Adverse Reactions in Seven Pooled 12-Week Controlled Trials
…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 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 (DESCARTES) 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.
Adverse Reactions in the Cardiovascular Outcomes Trial
In a double-blind, randomized, placebo-controlled cardiovascular outcomes trial (Study 1 [REPATHA Cardiovascular Outcomes Trial, FOURIER, NCT01764633]), 27,525 patients received at least one dose of REPATHA or placebo. 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 greater than or equal to 12 months, 54% were exposed for greater than or equal to 24 months and 5% were exposed for greater than or equal to 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 hyperlipidemia (including HeFH). Serious adverse events occurred in 24.8% and 24.7% of REPATHA-treated and placebo-treated patients, respectively. Adverse events led to discontinuation of study treatment in 4.4% of patients assigned to REPATHA and 4.2% assigned to placebo. 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 assigned to REPATHA compared with 7.7% in those assigned to placebo.
Adverse Reactions in Patients with Homozygous Familial Hypercholesterolemia
In a 12-week, double-blind, randomized, placebo-controlled trial of 49 patients with HoFH (Study 6 [TESLA, NCT01588496]), 33 patients received 420 mg of REPATHA subcutaneously once monthly. The mean age was 31 years (range: 13 to 57 years), 49% were women, 90% White, 4% Asian, and 6% other…
(Additions and/or revisions are underlined)
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including…
In a pool of placebo- and active-controlled clinical trials, 0.3% (48 out of 17,992) of patients treated with at least one dose of REPATHA tested positive for the development of binding antibodies.
8 Use in Specific Populations
8.1 Pregnancy(Additions and/or revisions are underlined)
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to REPATHA during pregnancy.
Please contact 1-877-311-8972 or https://mothertobaby.org/ongoing-study/repatha/ to enroll in or to obtain information about the registry.
(Additions and/or revisions are underlined)
In controlled trials, 7656 (41%) patients treated with REPATHA were ? 65 years old and 1500 (8%) were greater than or equal to 75 years old…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
…
Provide guidance to patients and caregivers on proper subcutaneous administration technique, including aseptic technique, and how to use the single-use prefilled autoinjector, single-use prefilled syringe, or single-use on-body infusor with prefilled cartridge correctly (see Instructions for Use leaflet). Inform patients that it may take up to 15 seconds to administer REPATHA using the single-use prefilled autoinjector or single-use prefilled syringe and about 9 minutes to administer REPATHA using the single-use on-body infusor with prefilled cartridge.
Advise latex-sensitive patients that the following components contain dry natural rubber (a derivative of latex) that may cause allergic reactions in individuals sensitive to latex: the needle cover of the glass single-use prefilled syringe and the single-use prefilled autoinjector.
The single-use on-body infusor with prefilled cartridge is not made with natural rubber latex.
(Additions and/or revisions are underlined)
What is REPATHA?
REPATHA is an injectable prescription medicine used:
in adults with cardiovascular disease to reduce the risk of heart attack, stroke, and certain types of heart surgery.
along with diet alone or together with other cholesterol-lowering medicines in adults with high blood cholesterol levels called primary hyperlipidemia (including a type of high cholesterol called heterozygous familial hypercholesterolemia) to reduce low density lipoprotein (LDL) or bad cholesterol.
What should I tell my healthcare provider before using REPATHA?
Before you start using REPATHA, tell your healthcare provider about all your medical conditions, including if you:
…The single-use Pushtronex system (on-body infusor with prefilled cartridge) is not made with natural rubber latex.
are pregnant or plan to become pregnant…
Pregnancy Registry. There is a pregnancy registry for women who take REPATHA during pregnancy. The purpose of this registry is to collect information about your health and your baby’s health. You can talk to your healthcare provider or contact 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/repatha/ to enroll in this registry or get more information.
…
Tell your healthcare provider or pharmacist about any prescription and over-the-counter medicines, vitamins, or herbal supplements you take.
How should I use REPATHA?
REPATHA comes as a single-use (1 time) prefilled autoinjector (SureClick® autoinjector), as a single-use prefilled syringe or as a single-use Pushtronex system (on-body infusor with prefilled cartridge). Your healthcare provider will prescribe the type and dose that is best for you.
If your healthcare provider prescribes you the monthly dose, you may use:
a single-use on-body infusor with prefilled cartridge to give the injection over 9 minutes, or
3 separate injections in a row, using a different single-use prefilled syringe or single-use prefilled autoinjector for each injection. Give all of these injections within 30 minutes.
If your healthcare provider decides that you or a caregiver can give REPATHA, you or your caregiver should receive training on the right way to prepare and inject REPATHA…
…
Always check the label of your single-use prefilled autoinjector, single-use prefilled syringe, or single-use on-body infusor with prefilled cartridge to make sure you have the correct medicine and the correct dose of REPATHA before each injection.
If you forget to use REPATHA or are not able to take the dose at the regular time, inject your missed dose as soon as you remember, as long as it is within 7 days of the missed dose.
If it is more than 7 days from the missed dose and you are using the every-2-week dose, inject the next dose based on your original schedule. This will put you back on your original schedule.
If it is more than 7 days from the missed dose and you are using the 1 time each-month dose, inject the dose and start a new schedule using this date.
If your healthcare provider has prescribed REPATHA along with other cholesterol-lowering medicines, follow instructions from your healthcare provider. Read the patient information for those medicines.
What are possible side effects of REPATHA?
REPATHA can cause serious side effects including:
allergic reactions. REPATHA may cause allergic reactions that can be serious.
The most common side effects of REPATHA include: runny nose, sore throat, symptoms of the common cold, flu or flu-like symptoms, back pain, high blood sugar levels (diabetes) and redness, pain, or bruising at the injection site.
12/01/2017 (SUPPL-14)
6 Adverse Reactions
6.1 Clinical Trials Experience(Additions and/or revisions are underlined)
Adverse Reactions in Adults with Primary Hyperlipidemia (including Heterozygous Familial Hypercholesterolemia)
…
Adverse Reactions in a 52-Week Controlled Trial
In a 52-week, double-blind, randomized, placebo-controlled trial (Study 3 [DESCARTES, NCT01516879]), 599 patients received 420 mg of REPATHA subcutaneously once monthly. 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 in DESCARTES, are shown in Table 1…
Table 1. Adverse Reactions Occurring in Greater than or Equal to 3% of REPATHA-treated Patients and More Frequently than with Placebo in DESCARTES
Adverse Reactions in Seven Pooled 12-Week Controlled Trials
…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 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 (DESCARTES) 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.
Adverse Reactions in the Cardiovascular Outcomes Trial
In a double-blind, randomized, placebo-controlled cardiovascular outcomes trial (Study 1 [REPATHA Cardiovascular Outcomes Trial, FOURIER, NCT01764633]), 27,525 patients received at least one dose of REPATHA or placebo. 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 greater than or equal to 12 months, 54% were exposed for greater than or equal to 24 months and 5% were exposed for greater than or equal to 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 hyperlipidemia (including HeFH). Serious adverse events occurred in 24.8% and 24.7% of REPATHA-treated and placebo-treated patients, respectively. Adverse events led to discontinuation of study treatment in 4.4% of patients assigned to REPATHA and 4.2% assigned to placebo. 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 assigned to REPATHA compared with 7.7% in those assigned to placebo.
Adverse Reactions in Patients with Homozygous Familial Hypercholesterolemia
In a 12-week, double-blind, randomized, placebo-controlled trial of 49 patients with HoFH (Study 6 [TESLA, NCT01588496]), 33 patients received 420 mg of REPATHA subcutaneously once monthly. The mean age was 31 years (range: 13 to 57 years), 49% were women, 90% White, 4% Asian, and 6% other…
(Additions and/or revisions are underlined)
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including…
In a pool of placebo- and active-controlled clinical trials, 0.3% (48 out of 17,992) of patients treated with at least one dose of REPATHA tested positive for the development of binding antibodies.
8 Use in Specific Populations
8.1 Pregnancy(Additions and/or revisions are underlined)
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to REPATHA during pregnancy.
Please contact 1-877-311-8972 or https://mothertobaby.org/ongoing-study/repatha/ to enroll in or to obtain information about the registry.
(Additions and/or revisions are underlined)
In controlled trials, 7656 (41%) patients treated with REPATHA were ? 65 years old and 1500 (8%) were greater than or equal to 75 years old…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
…
Provide guidance to patients and caregivers on proper subcutaneous administration technique, including aseptic technique, and how to use the single-use prefilled autoinjector, single-use prefilled syringe, or single-use on-body infusor with prefilled cartridge correctly (see Instructions for Use leaflet). Inform patients that it may take up to 15 seconds to administer REPATHA using the single-use prefilled autoinjector or single-use prefilled syringe and about 9 minutes to administer REPATHA using the single-use on-body infusor with prefilled cartridge.
Advise latex-sensitive patients that the following components contain dry natural rubber (a derivative of latex) that may cause allergic reactions in individuals sensitive to latex: the needle cover of the glass single-use prefilled syringe and the single-use prefilled autoinjector.
The single-use on-body infusor with prefilled cartridge is not made with natural rubber latex.
(Additions and/or revisions are underlined)
What is REPATHA?
REPATHA is an injectable prescription medicine used:
in adults with cardiovascular disease to reduce the risk of heart attack, stroke, and certain types of heart surgery.
along with diet alone or together with other cholesterol-lowering medicines in adults with high blood cholesterol levels called primary hyperlipidemia (including a type of high cholesterol called heterozygous familial hypercholesterolemia) to reduce low density lipoprotein (LDL) or bad cholesterol.
What should I tell my healthcare provider before using REPATHA?
Before you start using REPATHA, tell your healthcare provider about all your medical conditions, including if you:
…The single-use Pushtronex system (on-body infusor with prefilled cartridge) is not made with natural rubber latex.
are pregnant or plan to become pregnant…
Pregnancy Registry. There is a pregnancy registry for women who take REPATHA during pregnancy. The purpose of this registry is to collect information about your health and your baby’s health. You can talk to your healthcare provider or contact 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/repatha/ to enroll in this registry or get more information.
…
Tell your healthcare provider or pharmacist about any prescription and over-the-counter medicines, vitamins, or herbal supplements you take.
How should I use REPATHA?
REPATHA comes as a single-use (1 time) prefilled autoinjector (SureClick® autoinjector), as a single-use prefilled syringe or as a single-use Pushtronex system (on-body infusor with prefilled cartridge). Your healthcare provider will prescribe the type and dose that is best for you.
If your healthcare provider prescribes you the monthly dose, you may use:
a single-use on-body infusor with prefilled cartridge to give the injection over 9 minutes, or
3 separate injections in a row, using a different single-use prefilled syringe or single-use prefilled autoinjector for each injection. Give all of these injections within 30 minutes.
If your healthcare provider decides that you or a caregiver can give REPATHA, you or your caregiver should receive training on the right way to prepare and inject REPATHA…
…
Always check the label of your single-use prefilled autoinjector, single-use prefilled syringe, or single-use on-body infusor with prefilled cartridge to make sure you have the correct medicine and the correct dose of REPATHA before each injection.
If you forget to use REPATHA or are not able to take the dose at the regular time, inject your missed dose as soon as you remember, as long as it is within 7 days of the missed dose.
If it is more than 7 days from the missed dose and you are using the every-2-week dose, inject the next dose based on your original schedule. This will put you back on your original schedule.
If it is more than 7 days from the missed dose and you are using the 1 time each-month dose, inject the dose and start a new schedule using this date.
If your healthcare provider has prescribed REPATHA along with other cholesterol-lowering medicines, follow instructions from your healthcare provider. Read the patient information for those medicines.
What are possible side effects of REPATHA?
REPATHA can cause serious side effects including:
allergic reactions. REPATHA may cause allergic reactions that can be serious.
The most common side effects of REPATHA include: runny nose, sore throat, symptoms of the common cold, flu or flu-like symptoms, back pain, high blood sugar levels (diabetes) and redness, pain, or bruising at the injection site.
07/08/2016 (SUPPL-1)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PCI- Provide guidance to patients and caregivers on proper subcutaneous administration technique, including aseptic technique, and how to use the single-use prefilled autoinjector, single-use prefilled syringe, or single-use on-body infusor with prefilled cartridge correctly (see Instructions for Use leaflet). Inform patients that it may take up to 15 seconds to administer REPATHA using the single-use prefilled autoinjector or single-use prefilled syringe and about 9 minutes to administer REPATHA using the single-use on-body infusor with prefilled cartridge.
- The single-use on-body infusor with prefilled cartridge is not made with natural rubber latex.
See the detailed “Instructions for Use” that comes with this patient information about the right way to prepare and administer REPATHA. (additions are underlined below)
- REPATHA comes as a single-use (1 time) prefilled autoinjector (SureClick® autoinjector), as a single-use prefilled syringe or as a single-use PushtronexTM system (on-body infusor with prefilled cartridge).
- a single-use on-body infusor with prefilled cartridge over 9 minutes, or
Always check the label of your single-use prefilled autoinjector, single-use prefilled syringe, or single-use on-body infusor with prefilled cartridge to make sure you have the correct medicine and the correct dose of REPATHA before each administration. (new phrase underlined)