SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Forcinuit 1000 mg soft capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 1000 mg Omega-3-Acid Ethyl Esters 90, comprising 840 mg ethylesters of eicosapentaenoic acid (EPA) 460mg (46%) and docosahexaenoic acid (DHA) 380 mg (38%)

Excipient(s) with known effect: soybean oil (< 1.6 mg)

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Capsule, soft.

Oblong shaped, transparent, colourless soft gelatine capsule, filled with light yellowish oil.

4 CLINICAL PARTICULARS

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, - type IIb/III in combination with statins, when control of triglycerides is insufficient.

4.2 Posology and method of administration

Hypertriglyceridaemia

Initial treatment 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.

There is no information regarding the use of Omega-3-Acid Ethyl Esters in children, 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 or 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), patients receiving

anticoagulant therapy must be monitored and the dosage of anticoagulant adjusted if necessary (see section 4.5). 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.

Omega-3-Acid Ethyl Esters 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.

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).

4.5 Interaction with other medicinal products and other forms of interaction

Oral anticoagulants: See Section 4.4.

Omega-3-Acid Ethyl Esters has been given in conjunction with warfarin without haemorrhagic complications. However, the prothrombin time must be checked when Omega-3-Acid Ethyl Esters is combined with warfarin or when treatment with Omega-3-Acid Ethyl Esters is stopped.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of Omega-3-Acid Ethyl Esters 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 should not be used during pregnancy unless clearly necessary.

Lactation

There are no data on the excretion of Omega-3-Acide Ethyl Esters in animal and human milk. Omega-3-Acide Ethyl Esters should not be used during lactation.

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: 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).

Infections and infestations:

Uncommon: gastroenteritis Immune system disorders:

Uncommon: hypersensitivity Metabolism and nutrition disorders:

Rare: hyperglycaemia 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: Ill-defined disorders

Investigations:

Very rare: white blood count increased, blood lactate dehydrogenase increased

Moderate elevation of transaminases has been reported in patients with hypertriglyceridaemia.

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.

Omega-3-Acide Ethyl Esters is active on the plasma lipids by lowering triglyceride levels as a result of a fall in VLDL (very low densitylipoprotein), and the substance is also active on haemostasis and blood pressure.

Omega-3-Acide Ethyl Esters reduces 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-Acide Ethyl Esters increases 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-Acide Ethyl Esters, 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

No safety issues have been identified relevant to human use at the recommended daily intake.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Capsule _ fill:

alpha-tocopherol soybean oil sun flower oil

Capsule shell:

Glycerol

Gelatin

Medium-chain triglycerides (3-sn-Phosphatidyl)choline

6.2 Incompatibilities

Not applicable

6.3 Shelf life

2 years

6.4 Special precautions for storage

Blister

Store below 30°C. Store in the original packaging in order to protect from moisture.

HDPE bottle

Store below 30°C. Keep the bottle tightly closed in order to protect from moisture

6.5 Nature and contents of container

OPA-Al-PVC/Al blister containing 28, 30, 56, 90, 100, capsules

HDPE bottle, closed with LDPE cap, containing 28, 30, 56, 90,100 capsules

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7    MARKETING AUTHORISATION HOLDER

Sandoz Limited Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 04416/1229

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 13/08/2012

10 DATE OF REVISION OF THE TEXT

13/08/2012