Icosapent Ethyl

7 mmol/l]) and • established cardiovascular disease, or • diabetes, and at least one other cardiovascular risk factor. 1.

Posology The recommended daily oral dose is 4 capsules taken as two 998 mg capsules twice daily. If a dose is missed, patients should take it as soon as they remember. However, if one daily dose is missed, the next dose should not be doubled.

2). 2). 2). Paediatric population There is no relevant use of icosapent ethyl in children aged <18 years of age in reducing the risk of cardiovascular events in statin-treated patients at high cardiovascular risk with elevated triglycerides and other risk factors for cardiovascular disease.

Method of administration Oral use. Vazkepa should be taken with or following a meal. To ensure the full intended dose is received, patients should be advised to swallow the capsules whole and not to break, crush, dissolve, or chew them.

Tabulated list of adverse reactions Adverse reactions are classified according to frequency and system organ class. 9 years. Frequency categories are defined according to the following conventions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

. 9% in subjects receiving placebo. 4% vs. 4). 5%). 5% in subjects receiving placebo. Atrial fibrillation or atrial flutter requiring hospitalisation for 24 hours or more occurred in 3% of subjects treated with icosapent ethyl compared with 2% in subjects receiving placebo.

5% vs. 4). 6% of subjects receiving placebo. 2%). The relative incidence of constipation in this study may have been confounded by a residual laxative effect for placebo, which comprised a subtherapeutic dose of light mineral oil (4 mL).

The following adverse reactions have been identified from global post- marketing use of icosapent ethyl. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish causal relationship to drug exposure: blood triglycerides increased, arthralgia, diarrhoea, abdominal discomfort, and pain in the extremities.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

1.

1 INDICATIONS AND USAGE Icosapent ethyl capsules are indicated: as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.

Limitations of Use:

The effect of icosapent ethyl capsules on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. Icosapent ethyl capsules are an ethyl ester of eicosapentaenoic acid (EPA) indicated: as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.

(1) Limitations of Use: The effect of icosapent ethyl capsules on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. (1)

2 DOSAGE AND ADMINISTRATION Assess lipid levels before initiating therapy. Identify other causes of high triglyceride levels and manage as appropriate. 1) Patients should engage in appropriate nutritional intake and physical activity before receiving icosapent ethyl capsules, which should continue during treatment.

5 gram capsules twice daily with food or two 1 gram capsules twice daily with food. 2) Advise patients to swallow capsules whole. Do not break open, crush, dissolve, or chew icosapent ethyl capsules. 1 Prior to Initiation of Icosapent Ethyl Capsules Assess lipid levels before initiating therapy.

, diabetes mellitus, hypothyroidism, or medications) of high triglyceride levels and manage as appropriate. Patients should engage in appropriate nutritional intake and physical activity before receiving icosapent ethyl capsules, which should continue during treatment with icosapent ethyl capsules.

5 gram capsules twice daily with food; or as two 1 gram capsules twice daily with food. Advise patients to swallow icosapent ethyl capsules whole. Do not break open, crush, dissolve, or chew icosapent ethyl capsules.

3)] Common adverse reactions (incidence ≥3% and ≥1% more frequent than placebo): musculoskeletal pain, peripheral edema, constipation, gout, and atrial fibrillation. 1) Common adverse reactions in the hypertriglyceridemia trials (incidence ≥1% more frequent than placebo): arthralgia and oropharyngeal pain.

1) To report SUSPECTED ADVERSE REACTIONS, contact XLCare Pharmaceuticals, Inc. gov/medwatch. 1 Clinical 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 practice.

Common adverse reactions (incidence ≥3% on icosapent ethyl and ≥1% more frequent than placebo) included musculoskeletal pain, peripheral edema, constipation, gout, and atrial fibrillation. Hypertriglyceridemia Trials In two randomized, double-blind, placebo-controlled trials in patients with triglyceride levels between 200 and 2000 mg/dL treated for 12 weeks, adverse reactions reported with icosapent ethyl at an incidence ≥1% more frequent than placebo based on pooled data included arthralgia and oropharyngeal pain.

2 Postmarketing Experience Additional adverse reactions have been identified during post-approval use of icosapent ethyl capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Diarrhea Blood triglycerides increased Abdominal discomfort Pain in the extremities

, anaphylactic reaction) to icosapent ethyl or any of its components. , anaphylactic reaction) to icosapent ethyl or any of its components. (4)

7 mmol/L]) and • established cardiovascular disease, or • diabetes, and at least one other cardiovascular risk factor. 1.

Posology The recommended daily oral dose is 4 capsules taken as two 998 mg capsules twice daily. If a dose is missed, patients should take it as soon as they remember. However, if one daily dose is missed, the next dose should not be doubled.

2). 2). 2). 3 Paediatric population There is no relevant use of icosapent ethyl in children aged < 18 years of age in reducing the risk of cardiovascular events in statin-treated patients at high cardiovascular risk with elevated triglycerides and other risk factors for cardiovascular disease.

Method of administration Oral use. Vazkepa should be taken with or following a meal. To ensure the full intended dose is received, patients should be advised to swallow the capsules whole and not to break, crush, dissolve, or chew them.

0 %). Tabulated list of adverse reactions Adverse reactions are listed below and classified according to frequency and MedDRA system organ class based on all available interventional and non-interventional clinical trials and spontaneous reporting.

Frequency categories are defined according to the following conventions: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000) and not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 9 % in subjects receiving placebo. 4 % vs. 4). 5 %). 5 % in subjects receiving placebo. Atrial fibrillation or atrial flutter requiring hospitalisation for 24 hours or more occurred in 3 % of subjects treated with icosapent ethyl compared with 2 % in subjects receiving placebo.

5 % vs. 4). 6 % of subjects receiving placebo. 2 %). The relative incidence of constipation in this trial may have been confounded by a residual laxative effect for placebo, which comprised a subtherapeutic dose of light mineral oil (4 mL).

The following adverse reactions have been identified from global post-marketing use of icosapent ethyl. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish causal relationship to drug exposure: blood triglycerides increased, arthralgia, diarrhoea, abdominal discomfort, and pain in the extremities.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

1.

VASCEPA® (icosapent ethyl) is indicated to reduce the risk of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization or hospitalization for unstable angina) in statin-treated patients with elevated triglycerides, who are at high risk of cardiovascular events due to:  established cardiovascular disease, or  diabetes, and at least one other cardiovascular risk factor.

1 Pediatrics Pediatrics (<18 years): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use. 2 Geriatrics Geriatrics (≥65 years): VASCEPA may be used in patients ≥65 years of age.

Evidence from clinical studies and experience suggests that use in the geriatric population is not associated with differences in safety or effectiveness, but greater sensitivity of some older individuals cannot be ruled out.

1 Dosing Considerations  VASCEPA is to be administered together with statin treatment.  Patients should not take other omega-3 fatty acid products while they are taking VASCEPA without first consulting their attending physician.  Pregnancy should be ruled out prior to administration.

 Fish and/or shellfish hypersensitivity should be ruled out prior to administration.  Prior to initiation of VASCEPA: o Assess lipid levels before initiating therapy. , diabetes mellitus, hypothyroidism, or medications) of high triglyceride levels and manage as appropriate.

VASCEPA Product Monograph Page 5 of 24 o Patients should engage in appropriate nutritional intake and physical activity before receiving VASCEPA, which should continue during treatment with VASCEPA. 2 Recommended Dose and Dosage Adjustment  The dose of VASCEPA is 4 grams per day, taken as two 1 g capsules twice a day with food.

 Discontinue if anaphylactic/hypersensitivity reactions occur.  Health Canada has not authorized an indication for pediatric use (see 1 INDICATIONS). 4 Administration Patients should be advised to swallow VASCEPA capsules whole. Do not break open, crush, dissolve, or chew VASCEPA.

5 Missed Dose If a dose is missed, patients should take it as soon as they remember. However, if they miss one day of VASCEPA, they should not double the dose when they take their next dose.

1 Adverse Drug Reaction Overview The safety of VASCEPA was evaluated in 8,179 patients in the REDUCE-IT cardiovascular outcomes trial, with 4,089 randomized to VASCEPA and 4,090 patients randomized to placebo. 9 years. The overall adverse event rates were similar in patients treated with VASCEPA (82%), compared to placebo (81%), while the incidence of serious adverse events was the same in patients treated with VASCEPA (31%) and placebo (31%).

The rate of adverse events leading to discontinuation of study drug was also the same in patients treated with VASCEPA (8%) and placebo (8%). The most serious adverse reactions associated with VASCEPA were bleeding events (see Bleeding) and atrial fibrillation/flutter (see Cardiovascular).

3%). 2 Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may 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 is useful for identifying drug-related adverse events and for approximating rates. Adverse Reactions in the REDUCE-IT trial VASCEPA Product Monograph Page 9 of 24 In this double-blind, randomized, placebo-controlled cardiovascular outcomes trial, 4,089 patients were randomized to VASCEPA, and 4,090 to placebo (see 14 CLINICAL TRIALS).

The median age of enrolled patients was 64 years (range: 44 to 92 years), and 46% were 65 years of age or older. 2% identified as Hispanic ethnicity. 3 years; with 87% of patients for ≥12 months, 77% for ≥24 months, 65% for ≥36 months, 54% for ≥48 months, and 29% for ≥60 months.

004). 008). 006). 06). 15). 3 Less Common Clinical Trial Adverse Reactions The following less common adverse reactions at <5% in the VASCEPA group and at least 1% greater than in the placebo group are presented below. 4 Post-Market Adverse Reactions The following adverse reactions have been identified from global post-marketing use of VASCEPA.

Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish causal relationship to drug exposure: arthralgia, diarrhea, abdominal discomfo rt, and pain in the extremities.

, anaphylactic reaction) to VASCEPA 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.