Tomexia

Omega-3-acid ethyl capsules are supplied as 1 gram oblong, clear, soft gelatin capsules filled with light yellow liquid and imprinted with "PC25" in white ink.
Each Softgel Capsule contains: Eicosapentaenoic acid (EPA) Ethyl Ester 465 mg, Docosahexaenoic acid (DHA) Ethyl Ester 375 mg.

Pharmacotherapeutic group: Omega-3-triglycerides including other esters and acids. ATC code: C10AX06.
Pharmacology: Pharmacodynamics: The omega-3 series polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential fatty acids.
TOMEXIA is 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 hemostasis and blood pressure.
TOMEXIA 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 β-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.
TOMEXIA increases LDL-cholesterol in some patients with hypertriglyceridemia. 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 ischemic heart disease.
During treatment with TOMEXIA, 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.
Pharmacokinetics: 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 channeled 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 oxidized 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.

For isolated or predominant endogenous hypertriglyceridemia in patient at risk of ischemic heart disease and or pancreatitis.
Endogenous hypertriglyceridemia as a supplement to diet when dietary measures alone are insufficient to produce an adequate response: type IV in monotherapy; type llb/III in combination with statins, when control of triglycerides is insufficient.

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.

Symptoms: There are no special recommendations for overdosage of TOMEXIA.
Treatment: Treatment should be symptomatic. If symptoms persist consult the doctor.

Hypersensitivity to the active substance, to soya or to any of the excipients. TOMEXIA contains soya oil. If the patient is allergic to peanut or soya, do not use this medicinal product.

TOMEXIA should be used with caution in patients with known sensitivity or allergy to fish.
In the absence of efficacy and safety data, use of this medication in children is not recommended. Clinical data regarding the use of TOMEXIA in elderly patients over 70 years of age are limited.
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. 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 hemorrhage (because of severe trauma, surgery, etc).
During treatment with TOMEXIA, 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.
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).
TOMEXIA is not indicated in exogenous hypertriglyceridemia (type 1 hyperchylomicronemia). There is only limited experience in secondary endogenous hypertriglyceridemia (especially uncontrolled diabetes).
There is no experience regarding hypertriglyceridemia in combination with fibrates.

Pregnancy: Category B1: There are no adequate data from the use of TOMEXIA in pregnant women. The potential risk for humans is unknown. Therefore TOMEXIA should not be used during pregnancy unless clearly necessary.
Lactation: There are no data on the excretion of TOMEXIA components in human milk. Because many drugs are excreted in human milk, caution should be exercised when TOMEXIA is administered to a woman who is breastfeeding.

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.
Immune system disorders: Rare: Hypersensitivity.
Metabolism and nutrition disorders: Uncommon: Hyperglycemia, 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-esophageal reflux disease, nausea or vomiting).
Uncommon: Gastrointestinal hemorrhage.
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: Pruritus.

Increased bleeding time has been seen when TOMEXIA is given in conjunction with acetylsalicylic acid and warfarin, but without hemorrhagic complications (see Precautions).
Acetylsalicylic acid: Patients should be informed about potential increased bleeding time.
Warfarin and coumarin: The prothrombin time/international normalized ratio (PT/INR) must be monitored during combination treatment with TOMEXIA among patients receiving blood-thinning therapy, and when treatment with TOMEXIA is discontinued.
Statins: TOMEXIA has been administered with simvastatin 80 mg under fasting conditions to 24 healthy volunteers in a two 14-days period drug-drug interaction study. Results of this study demonstrated that at steady state, the co-administration of TOMEXIA capsules with simvastatin did not appear to affect the pharmacokinetics of simvastatin tablets.
The combination appeared to be well tolerated. TOMEXIA has been given in conjunction with warfarin without hemorrhagic complications. However, the prothrombin time must be checked when TOMEXIA is combined with warfarin or when treatment with TOMEXIA is stopped.

Store at temperatures not exceeding 30°C.
Shelf-Life: 36 months.

Dyslipidaemic Agents

C10AX06 - omega-3-triglycerides incl. other esters and acids ; Belongs to the class of other lipid modifying agents.

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