TREDAPTIVE ® Nicotinic acid and laropiprant

PLEASE NOTE: MEDICINAL PRODUCT IS NO LONGER AUTHORIZED

TREDAPTIVE ® is a drug based on nicotinic acid and laropiprant.

THERAPEUTIC GROUP: Hypolipidemic - Synthetic analogue of nicotinic acid

IndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects

Indications TREDAPTIVE ® Nicotinic acid and laropiprant

TREDAPTIVE ® is used in the treatment of mixed dyslipidemia, characterized by high levels of triglycerides and LDL cholesterol, and in the treatment of heterozygous familial hypercholesterolemia.

TREDAPTIVE ® should be administered in synergy with statins, or as monotherapy, to patients who are not responsive to treatment with HMG-CoA reductase inhibitors.

Like any lipid-lowering treatment, the use of TREDAPTIVE ® must be preceded and accompanied by a hypolipidic diet and constant exercise.

Mechanism of action TREDAPTIVE ® Nicotinic acid and laropiprant

TREDAPTIVE ® taken orally, is absorbed at the gastro-intestinal level, causing a plasmatic peak of its active ingredients after about 4 hours. Bioavailability, for both nicotinic acid and laropiprant, is around 70% of the dose taken. Both active ingredients undergo a first-pass metabolism: at low doses nicotinic acid gives rise to nicotinamide, while once saturated this pathway produces nicotinuric acid (by conjugation with glycine); laropiprant is instead conjugated to acyl glucoronide, with partial reduction of its biological functionality.

The lipid-lowering effects of the drug are due solely to the action of nicotinic acid. Once the adipose tissue linked to glycine is reached, this active principle can in fact interact with orphan receptors and - through cellular events that have not yet been clarified - inhibit lipolysis and the release of fatty acids in the blood stream.

The reduced influx of fatty acids not conjugated to the liver leads to a significant reduction in the hepatic synthesis of triglycerides and lipoproteins (VLDL and LDL), helping to rebalance the lipidemic profile.

All these events - accompanied by an increase in HDL cholesterol and the gradual replacement of small and dense LDL cholesterol particles (strongly atherogenic) with larger lipoproteins - guarantee a reduction in cardiovascular risk.

The high concentrations of nicotinic acid necessary to guarantee the lipid-lowering effect are systematically accompanied by an unpleasant side effect, supported by the increased production of prostaglandin D2 and characterized by hot flushes. Laropiprant acts at this level, blocking the DP1 receptor for prostaglandin D2 and preventing the cutaneous vasodilatory action from causing flushing.

After the therapeutic effect, the nicotinic acid is eliminated mainly through the urine, while the laropiprant mainly through the feces.

Studies carried out and clinical efficacy

THE MEANING OF THE ASSOCIATION OF NICOTINIC ACID / LAROPIPRANT

Nicotinic acid is among the most effective drugs in reducing the cardiovascular risk associated with hyperlipidemia. This characteristic is given above all by the possibility of significantly increasing HDL cholesterol levels. Despite this, nicotinic acid recognizes limits due essentially to the high dosage required, which very often causes side effects such as the classic hot flashes. The association with laropiprant significantly reduces the side effects of nicotinic acid, safeguarding its therapeutic efficacy.

2. THE EFFECTIVENESS OF TREDAPTIVE

The efficacy of the combination of extended release nicotinic acid and laropiprant was evaluated in almost 1500 patients undergoing therapy. The results obtained after 20 weeks of treatment with 2 grams of nicotinic acid and 40 mg of laropiprant, have been quite positive. An average reduction in LDL cholesterol of 18%, triglycerides of 26% and total cholesterol of 8% was recorded, while HDL cholesterol increased by 20%.

3. COMBINATION OF NICOTINIC ACID / LAROPIPRANT / SIMVASTATIN

The association of simvastatin with the nicotinic acid / laropiprant combination could complete the therapeutic efficacy of the lipid-lowering cure, guaranteeing a synergistic and complementary action. In fact, while nicotinic acid could guarantee a significant increase in HDL cholesterol, simvastatin could break down LDL. Therefore, this therapeutic combination would ensure a significant reduction in cardiovascular risk. One of the most important limitations of such a therapy lies in the potential increase in the risk of developing liver disease and rhabdomyolysis.

Method of use and dosage

TREDAPTIVE ® modified release tablets containing 1000 mg of nicotinic acid and 20 mg of laropiprant: in the first four weeks of treatment the dosage should be one tablet a day, then rise to 2 daily tablets taken in a single administration.

Taking TREDAPTIVE ® is preferable in the evening, during dinner or before going to bed, in order to preserve the pharmacokinetic properties of the product.

Before and during the pharmacological intervention with TREDAPTIVE ® it is advisable to follow a healthy lifestyle and a hypolipid food plan.

IN ANY CASE, BEFORE TAKING TREDAPTIVE ® Nicotinic Acid and Laropiprant - THE PRESCRIPTION AND CONTROL OF ITS OWN DOCTOR IS NECESSARY.

Warnings TREDAPTIVE ® Nicotinic acid and laropiprant

Before and while taking TREDAPTIVE ® it is advisable to pursue non-pharmacological interventions (hypolipid diet and physical activity) aimed at decreasing the lipid content in the blood. If the administration of the drug is necessary, the doctor should investigate the patient's liver and muscle function, evaluating whether or not to undertake therapy in the event of impaired liver and muscle function, or a predisposition to the onset of such diseases. These precautions are necessary in order to avoid adverse reactions of the liver and skeletal muscle, documented in the literature and particularly frequent in the case of concomitant administration of HMG-CoA reductase inhibitors.

Given the urinary excretion of nicotinic acid, and its effects on some hematoclinic parameters, it is advisable to monitor the functional capacity of the kidneys, fasting glucose, uric acid and phosphate concentrations, and platelet count before and during treatment. .

The presence of lactose among the excipients of TREDAPTIVE ® could be responsible for adverse gastro-intestinal drug reactions, common in patients suffering from glucose / galactose malabsorption or lactase enzyme deficiency.

Although no interference has been described on the patient's normal perceptive abilities, the presence of dizziness - which is frequent especially at the beginning of treatment with TREDAPTIVE ® may compromise the normal ability to drive vehicles and use machinery.

PREGNANCY AND BREASTFEEDING

The use of TREDAPTIVE ® during pregnancy and lactation is not recommended, given the lack of useful studies to understand the safety profile of the drug on the health of the fetus, newborn and pregnant women.

Interactions

The presence of two different active ingredients significantly increases the possible interactions that the drug TREDAPTIVE ® can take with other biologically active molecules.

In fact, at high doses, nicotinic acid can interact with:

Antihypertensive drugs of various kinds, strengthening their hypotensive efficacy;
Statins, increasing the lipid-lowering effect;
Agents sequestering bile acids, losing part of its active altitude.

The interactions observed for laropiprant were not significant from either the pharmacokinetic or clinical point of view.

Contraindications TREDAPTIVE ® Nicotinic acid and laropiprant

TREDAPTIVE ® is contraindicated in case of reduced hepatic or renal function, in case of active peptic ulcer, arterial bleeding and hypersensitivity to one of its compounds.

Undesirable effects - Side effects

Adverse reactions reported by patients treated with TREDAPTIVE ® were generally transient and mild.

Hot flashes, dizziness, headache, diarrhea, nausea, vomiting, erythema, pruritus, rash and changes in blood parameters of transaminase, blood sugar and uric acid, were the most described side effects.

Hypersensitivity reactions and clinically more relevant side effects were found only in a few cases, generally in categories of patients defined as at risk.