Trevaclyn

PLEASE NOTE: MEDICINAL PRODUCT IS NO LONGER AUTHORIZED

What is Trevaclyn?

Trevaclyn is a medicine containing two active substances: nicotinic acid (also known as niacin or vitamin B3) and laropiprant. The medicine is available as modified release tablets. "Modified release" means that the two active ingredients are released from the tablet at different speeds over the course of a few hours.

What is Trevaclyn used for?

Trevaclyn is used as an adjunct to diet and physical activity in patients with dyslipidemia (exceptionally high levels of fat in the blood), particularly for 'mixed combined dyslipidemia' and 'primary hypercholesterolemia'. Patients with mixed combined dyslipidemia have high levels of 'bad' cholesterol (LDL) and triglycerides (a type of fat) and low levels of 'good' cholesterol (HDL) in the blood. Primary hypercholesterolemia is a condition in which the concentration of cholesterol in the blood is high. By 'primary' we mean that hypercholesterolemia does not have an identifiable cause.

Trevaclyn is normally prescribed together with a statin (the standard medicine used to reduce cholesterol) when the effectiveness of statin alone is insufficient. Trevaclyn is used on its own exclusively in patients who cannot take statins.

The medicine can only be obtained with a prescription.

How is Trevaclyn used?

The starting dose of Trevaclyn is one tablet once a day for four weeks; subsequently the dose is increased to two tablets once a day. The medicine is taken orally, with food, in the evening or before going to bed. The tablets must be swallowed whole and must not be divided, broken, crushed or chewed.

The use of Trevaclyn is not recommended for children under the age of 18 due to the lack of information on the safety and efficacy profile of the medicine in this group. The medicine should be used with caution in patients with kidney problems and should not be used in patients with liver problems.

How does Trevaclyn work?

The two active ingredients of Trevaclyn, nicotinic acid and laropiprant, have different mechanisms of action.

Nicotinic acid is a naturally occurring substance that is used in low doses as a vitamin. At higher doses, it reduces the level of fat in the blood through a mechanism not yet perfectly

clear. The substance was used for the first time as a medicine that could change the concentration of fat in the blood in the mid-1950s but its use was limited due to side effects, particularly flushing (redness of the skin).

It is believed that the flushes associated with nicotinic acid depend on the release by the skin cells of a substance called 'prostaglandin D2' (PGD2) which dilates (widens) the blood vessels of the skin. Laropiprant blocks the receptors to which PGD2 normally attaches. If the receptors are blocked, PGD2 fails to dilate the vessels in the skin and the frequency and intensity of hot flashes are reduced.

In Trevaclyn tablets, laropiprant is found in one of the layers. The other layer contains nicotinic acid. When the patient takes the tablet, laropiprant is released into the bloodstream first and blocks the PGD2 receptors. Nicotinic acid is released more slowly from the other layer and exerts the action of a drug that modifies the lipid profile.

What studies have been carried out on Trevaclyn?

The effects of Trevaclyn were first tested in experimental models before being studied in humans.

Trevaclyn has been studied in four main studies conducted in patients with hypercholesterolemia or mixed dyslipidemia.

Two studies observed Trevaclyn's ability to change blood fat levels. The first study compared the effectiveness of Trevaclyn with that of nicotinic acid alone or placebo (a dummy treatment) in reducing LDL cholesterol levels in a total of 1, 613 patients. The study also examined the symptoms of hot flashes using a special questionnaire.

The second study compared the combination of Trevaclyn and simvastatin (a statin) with Trevaclyn alone or simvastatin alone in 1 398 patients. The main measure of effectiveness was the change in blood LDL cholesterol levels after 12 weeks.

The third and fourth studies looked at the effectiveness of laropiprant in reducing flushing caused by nicotinic acid. They included a total of 2 349 patients alternately taking Trevaclyn or nicotinic acid. The flushes were measured using the questionnaire on the symptoms of hot flashes.

What benefit has Trevaclyn shown during the studies?

Trevaclyn has been shown to be effective in reducing blood LDL cholesterol levels. In the first study, LDL cholesterol levels were reduced by 19% in patients taking Trevaclyn, compared with 1% of those taking placebo. The second study showed that LDL cholesterol levels were further reduced when Trevaclyn was taken together with simvastatin (48% reduction), compared to Trevaclyn alone (17% reduction) or simvastatin alone (37% reduction).

The addition of laropiprant to nicotinic acid reduced the symptoms of flushing caused by nicotinic acid. In the first and third studies, fewer patients taking Trevaclyn reported moderate, severe or extreme flushing compared to patients taking nicotinic acid alone. In the fourth study, flushing was observed in fewer days in patients taking Trevaclyn than in those taking nicotinic acid alone.

What is the risk associated with Trevaclyn?

The most common side effects with Trevaclyn (seen in more than 1 patient in 10) are hot flushes. For the full list of all side effects reported with Trevaclyn, see the Package Leaflet.

Trevaclyn should not be used in people who may be hypersensitive (allergic) to nicotinic acid, laropiprant or any of the other ingredients. In addition, the medicine should not be used in patients with liver problems, active gastric ulcer or arterial bleeding.

Why has Trevaclyn been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Trevaclyn's benefits are greater than its risks for the treatment of dyslipidemia, particularly in patients with mixed combined dyslipidemia and in patients with primary hypercholesterolaemia. The Committee recommended that Trevaclyn be given marketing authorization.