Omega 3-Acid-Ethyl Esters 1000mg Soft Capsules
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Omega 3-acid-ethyl esters 1000mg soft capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One capsule contains 1000 mg Omega-3-Acid Ethyl Esters 90, comprising principally 840 mg ethylesters of eicosapentaenoic acid (EPA) (465 mg) and docosahexaenoic acid (DHA) (375 mg).
Excipient with known effect: Lecithin (soya)
For a full list of excipients see section 6.1.
3 PHARMACEUTICAL FORM
Capsule, soft.
Soft, oblong, transparent gelatin capsule containing pale yellow coloured oily liquid imprinted with ‘740’.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Post Myocardial Infarction
Adjuvant treatment in secondary prevention after myocardial infarction, in addition to other standard therapy (e.g. statins, anti-platelet medicinal products, beta-blockers, ACE inhibitors).
Hypertriglyceridaemia
Endogenous hypertriglyceridaemia as a supplement to diet when dietary measures alone are insufficient to produce an adequate response:
- type IV in monotherapy,
- typellb/III in combination with statins, when control of triglycerides is insufficient.
4.2 Posology and method of administration
Adults
Post Myocardial Infarction
One capsule daily.
Hypertriglyceridaemia
Initial treatment is two capsules daily. If adequate response is not obtained, the dose may be increased to four capsules daily.
The capsules may be taken with food to avoid gastrointestinal disturbances.
Special populations
There is no information regarding the use of Omega 3-acid-ethyl esters Strides 1000mg soft capsules in children and adolescents, in elderly patients over 70 years of age, or in patients with hepatic impairment (see section 4.4), and only limited information regarding the use in patients with renal impairment.
4.3 Contraindications
Hypersensitivity to the active substance, to soya, peanut or to any of the excipients listed in section 6.1
4.4 Special warnings and precautions for use
Warnings
Because of the moderate increase in bleeding time (with the high dosage, i.e. 4 capsules per day), patients receiving anticoagulant therapy must be monitored and the dosage of anticoagulant adjusted if necessary (see section 4.5 Interaction with other Medicinal Products and other forms of Interaction). Use of this medication does not eliminate the need for the surveillance usually required for patients of this type.
Make allowance for the increased bleeding time in patients at high risk of haemorrhage (because of severe trauma, surgery, etc).
This medicinal product contains lecithin (soya). If the patient is allergic to peanut or soya, do not take this medicinal product (see section 4.3).
Paediatric population
In the absence of efficacy and safety data, use of this medication in children and adolescents is not recommended.
Omega-3-acid ethyl esters 90 is not indicated in exogenous hypertriglyceridaemia (type 1 hyperchylomicronaemia). There is only limited experience in secondary endogenous hypertriglyceridaemia (especially uncontrolled diabetes).
There is no experience regarding the treatment of hypertriglyceridaemia in combination with fibrates.
Special precaution
Regular monitoring of hepatic function (ASAT and ALAT) is required in patients with hepatic impairment (in particular with the high dosage, i.e. 4 capsules per day).
4.5 Interaction with other medicinal products and other forms of interaction
Oral anticoagulants: See Section 4.4 Special warnings and precautions for use.
Omega-3-acid ethyl esters 90 have been given in conjunction with warfarin without haemorrhagic complications. However, the prothrombin time must be checked when Omega-3-acid ethyl esters 90 are combined with warfarin or when treatment with Omega-3-acid ethyl esters 90 is stopped.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no adequate data from the use of Omega-3-acid ethyl esters 90 in pregnant women.
Studies in animals have not shown reproductive toxicity. The potential risk for humans is unknown and therefore Omega-3-acid ethyl esters 90 should not be used during pregnancy unless clearly necessary.
Lactation
There are no data on the excretion of Omega-3-acid ethyl esters 90 in animal and human milk. Omega-3-acid ethyl esters 90 should not be used during lactation.
Fertility
No data available
4.7 Effects on ability to drive and use machines
Not relevant.
4.8 Undesirable effects
The frequencies of adverse reactions are ranked according to the following: common (> 1/100, < 1/10); uncommon (>1/1000 < 1/100); rare (>1/10000, < 1/1000); very rare (< 1/10000), including isolated reports.
Infection and infestations
Uncommon: gastroenteritis Immune system disorders:
Uncommon: hypersensitivity
Metabolism and nutrition disorders:
Rare: hyperglycemia
Nervous system disorders:
Uncommon: dizziness, dysgeusia Rare: headache
Vascular disorders:
Very rare: hypotension
Respiratory thoracic and mediastinal disorders:
Very rare: nasal dryness Gastrointestinal disorders:
Common: dyspepsia, nausea
Uncommon: abdominal pain, gastrointestinal disorders, gastritis, abdominal pain upper
Rare: gastrointestinal pain
Very rare: lower gastrointestinal haemorrhage
Hepatobiliary disorders:
Rare: hepatic disorders
Skin and subcutaneous tissue disorders:
Rare: acne, rash pruritic Very rare: urticaria
General disorders and administration site conditions:
Rare: III-defined disorders Investigations:
Very rare: white blood count increased, blood lactate dehydrogenase increased
Moderate elevation of transaminases has been reported in patients with hypertriglyceridaemia.
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
There are no special recommendations. Administer symptomatic treatment.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other lipid modifying agents, omega-3-triglycerides, incl. other esters and acids; ATC code: C10AX06.
The omega-3 series polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential fatty acids.
Mechanism of action
Omega-3-acid ethyl esters 90 are active on the plasma lipids by lowering triglyceride levels as a result of a fall in VLDL (very low density lipoprotein), and the substance is also active on haemostasis and blood pressure.
Pharmacodynamic effects
Omega-3-acid ethyl esters 90 reduce the synthesis of triglycerides in the liver because EPA and DHA are poor substrates for the enzymes responsible for triglyceride synthesis and they inhibit esterification of other fatty acids.
The increase in peroxisomes of P-oxidation of fatty acids in the liver also contributes to the fall in triglycerides, by reducing the quantity of free fatty acids available for their synthesis. The inhibition of this synthesis lowers VLDL.
Omega-3-acid ethyl esters 90 increase LDL-cholesterol in some patients with hypertriglyceridaemia. A rise in HDL-cholesterol is only small, significantly smaller than seen after administration of fibrates, and not consistent.
The long-term lipid-lowering effect (after more than one year) is not known. Otherwise there is no strong evidence that lowering triglycerides reduces the risk of ischaemic heart disease.
During treatment with Omega-3-acid ethyl esters 90, there is a fall in thromboxane A2 production and a slight increase in b leeding time. No significant effect has been observed on the other coagulation factors.
Clinical efficacy and sa/ety!1324 patients, with recent MI (<3 months) and receiving a recommended preventative treatment associated with a Mediterranean diet, were randomised in the GISSI-Prevenzione study in order to receive Omega-3-acid ethyl esters 90 (n=2836), vitamin E (n=2830), Omega-3-acid ethyl esters 90 + vitamin E (n=2830) or no treatment (n=2828). GISSI-P was a multicentre, randomised, open-label study performed in Italy.
The results observed over 3.5 years, with Omega-3-acid ethyl esters 90 1g/day, have shown a significant reduction of a combined endpoint including all-cause death, non fatal MI and non fatal stroke (decrease in relative risk of 15% [2-26] p=0.0226 in patients taking Omega-3-acid ethyl esters 90 alone compared to control, and of 10% [1-18] p=0.0482 in patients taking Omega-3-acid ethyl esters 90 with or without vitamin E). A reduction of the second pre-specified endpoint criteria including cardiovascular deaths, non fatal MI and non-fatal stroke has been shown (decrease in relative risk of 20% [5-32] p=0.0082 in patients taking Omega-3-acid ethyl esters 90 alone compared to control, decrease in relative risk of 11% [1-20] p= 0.0526 in patients taking Omega-3-acid ethyl esters 90 with or without vitamin E). The secondary analysis for each component of the primary endpoints has shown a significant reduction of all cause deaths and cardiovascular deaths, but no reduction of non fatal cardiovascular events or fatal and non fatal strokes.
5.2 Pharmacokinetic properties
During and after absorption, there are three main pathways for the metabolism of the omega-3 fatty acids:
- the fatty acids are first transported to the liver where they are incorporated into various categories of lipoproteins and then channelled to the peripheral lipid stores;
- the cell membrane phospholipids are replaced by lipoprotein phospholipids and the fatty acids can then act as precursors for various eicosanoids;
- the majority is oxidised to meet energy requirements.
The concentration of omega-3 fatty acids, EPA and DHA, in the plasma phospholipids corresponds to the EPA and DHA incorporated into the cell membranes.
Animal pharmacokinetic studies have shown that there is a complete hydrolysis of the ethyl ester accompanied by satisfactory absorption and incorporation of EPA and DHA into the plasma phospholipids and cholesterol esters.
5.3 Preclinical safety data
No safety issues have been identified relevant to human use at the recommended daily intake.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule core:
Alpha-tocopherol
Capsule shell:
Gelatin Glycerol purified water Medium-chain triglycerides Isopropyl alcohol
Opacode white printing ink
(Composition of Opacode white ink is Shellac glaze, Titanium dioxide, Purified water, N-butyl alcohol, Lecithin (soya), Simeticone)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
24 months.
Shelf life after first opening of HDPE container is 120 days.
6.4 Special precautions for storage
Store below 30oC.
Keep the container in the outer carton in order to protect from the light. For shelf life after first opening of HDPE please refer section 6.3.
6.5 Nature and contents of container
White opaque HDPE container with white opaque HDPE screw closure with induction sealing. Each bottle contains 20, 28, 100 and 120 capsules.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Strides Arcolab International Limited Unit 4, Metro Centre, Tolpits Lane,
Watford, Hertfordshire WD 189 SS United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 28176/0145
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15/07/2014
10 DATE OF REVISION OF THE TEXT
15/07/2014