TEROMEG 1000 MG CAPSULES - Summary of medicine characteristics

Teromeg 1000 mg Capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 1000 mg Omega-3-Acid Ethyl Esters 90, comprising principally 840 mg ethylesters of eicosapentaenoic acid (EPA) 460 mg and docosahexaenoic acid (DHA) 380 mg.

For a full list of excipients see section 6.1.

3 PHARMACEUTICAL FORM

Capsule, soft.

Slightly yellow soft capsules.

4.1 Therapeutic indications

Hypertriglyce­ridaemia

Endogenous hypertriglyce­ridaemia as a supplement to diet when dietary measures alone are insufficient to produce an adequate response:

– type IV in monotherapy,

– typeIIb/III in combination with statins, when control of triglycerides is insufficient.

4.2 Posology and method of administration

Posology

Hypertriglyce­ridaemia

Initial treatment two capsules daily. If adequate response is not obtained, the dose may be increased to four capsules daily.

Older people (Over the age of 70 years)

There is limited clinical data regarding the use of Teromeg 1000 mg Capsules.

Renal Impairment

There is limited clinical data regarding the use of Teromeg 1000 mg Capsules (see section

4.4).

Hepatic Impairment

There is no information regarding the use of Teromeg 1000 mg Capsules in patients with hepatic impairment (see section 4.4).

Paediatric population and adolescents

There is no information regarding the use of Teromeg 1000 mg Capsules in children and adolescents.

Method of administration

The capsules may be taken with food to avoid gastrointestinal disturbances.

4.3 Contraindications

Hypersensitivity to the active substance, to soya or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Because of the moderate increase in bleeding time (with the high dosage, i.e. 4 capsules), 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).

In the absence of efficacy and safety data, use of this medication in children is not recommended.

During treatment with Omega 3-acid-ethyl esters 90, there is a fall in thromboxane A2 production. No significant effect has been observed on the other coagulation factors. Some studies with omega-3-acids demonstrated a prolongation of bleeding time, but the bleeding time reported in these studies has not exceeded normal limits and did not produce clinically significant bleeding episodes.

Clinical data regarding the use of Omega 3-acid-ethyl esters 90 in elderly patients over 70 years of age are limited.

Only limited information regarding the use in patients with renal impairment is available.

In some patients a small but significant increase (within normal values) in ASAT and ALAT was reported, but there are no data indicating an increased risk for patients with hepatic impairment. ALAT and ASAT levels should be monitored in patients with any signs of liver damage (in particular with the high dosage, i.e. 4 capsules).

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 hypertriglyce­ridaemia in combination with fibrates.

Teromeg capsules should be used with caution in patients with known sensitivity or allergy to fish.

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 are stopped.

4.6 Fertility, pregnancy and lactation

Pregnancy

Adequate data from the use of Omega-3-acid ethyl esters 90 in pregnant women is not available.

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.

Breast-feeding

No data on the excretion of Omega-3-acid ethyl esters 90 in animal and human milk is available. Omega-3-acid ethyl esters 90 should not be used during lactation.

4.7 Effects on ability to drive and use machines

Effects on ability to drive and use machines have not been studied.

Nevertheless, Omega-3-acid ethyl esters 90 is expected to have no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

The frequencies of adverse reactions are ranked according to the following:

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)__­________________________­___________________

Not known (cannot be estimated from the available data)

Immune system disorders:

Rare: hypersensitivity

Metabolism and nutrition disorders:

Uncommon: hyperglycaemia, gout

Nervous system disorders:

Uncommon: dizziness, dysgeusia, headache

Vascular disorders:

Uncommon: hypotension

Respiratory thoracic and mediastinal disorders:

Uncommon: epistaxis

Gastrointestinal disorders:

Common: gastrointestinal disorders (including abdominal distension, abdominal pain, constipation, diarrhea, dyspepsia, flatulence, eructation, gastro-oesophageal reflux disease, nausea or vomiting)

Uncommon: gastrointestinal haemorrhage

Hepatobiliary disorders:

Rare: liver disorders (including transaminases increased, alanine aminotransferase increased and aspartate aminotransferase increased)

Skin and subcutaneous tissue disorders:

Uncommon: rash

Rare : urticaria

Not known (cannot be estimated from the available data): Pruritus

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. Website: www.mhra.gov.uk/yellowcard

4.9 Overdose

There are no special recommendations.

Treatment should be symptomatic.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: omega-3-triglycerides, including 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.

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.

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.

During treatment with Omega-3-acid ethyl esters 90, there is a fall in thromboxane A2 production and a slight increase in bleeding time. No significant effect has been observed on the other coagulation factors.

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

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology ,of repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development. In addition non-clinical literature data on safety pharmacology are indicating that there is no hazard for humans.

6.1 List of excipients

Capsule core:

Alpha-tocopherol (may contain vegetable oil e.g. soya oil)

Capsule shell:

Gelatin

Glycerol

purified water

Medium-chain triglycerides

Lecithin (sunflower)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

48 months.

Teromeg 1000 mg Capsules should be used within 100 days of opening the bottle.

6.4 Special precautions for storage

Do not store above 25°C. Do not freeze.

For storage conditions after 1st opening of the medicinal product, see section 6.3.

6.5 Nature and contents of container

White (HDPE) bottle

– 1 × 20 sof. g. capsules

– 1 × 28 sof. g. capsules

– 1 × 30 sof. g. capsules

– 1 × 60 sof. g. capsules

– 1 × 100 sof. g. capsules

– 10 × 28 sof. g. capsules

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Mercury Pharmaceuticals Ltd.,

Capital House, 85 King William Street,

London EC4N 7BL, UK.

8 MARKETING AUTHORISATION NUMBER(S)

PL 12762/0473

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

29/08/2012