What is Tredaptive?
Tredaptive is a medicine containing two active substances: nicotinic acid (also known as niacin or vitamin B3) and laropiprant. It is available as modified release tablets. "Modified release" means the fact that the two active ingredients are released from the tablet at a differentiated speed over a few hours.
What is Tredaptive used for?
Tredaptive is used as an adjunct to diet and exercise in patients with dyslipidemia (excessively high levels of fat in the blood), particularly with "combined combined dyslipidemia" and "primary hypercholesterolemia". Patients suffering from combined mixed dyslipidemia have high levels of LDL cholesterol (so-called "bad") and triglycerides (a type of fat) and low levels of HDL cholesterol (so-called "good") in the blood. Primary hypercholesterolemia refers to the condition in which blood cholesterol levels are high; by "primary" we mean the fact that hypercholesterolemia is not due to a specific cause.
Tredaptive is usually given together with a statin (the standard cholesterol-lowering drug) in cases where the statin alone is not sufficiently effective. Tredaptive is used alone in patients who cannot take statins.
The medicine can only be obtained with a prescription.
How is Tredaptive used?
The starting dose of Tredaptive is one tablet once a day for four weeks, after which the dose is taken to two tablets a day. The tablet should be taken by mouth with food, in the evening or before bedtime, and it should be swallowed whole, that is without dividing it, breaking it, crushing it or chewing it. Tredaptive is not recommended for use in young people under the age of 18 due to the lack of safety and efficacy information for this group. It should also be used with caution in patients with kidney problems and should not be used in patients with liver problems.
How does Tredaptive work?
The two active ingredients of Tredaptive, nicotinic acid and laropiprant, have different modes of action.
Nicotinic acid is a naturally occurring substance that is used as a vitamin at low doses. At high doses it reduces blood fat levels according to a mechanism not yet fully known. The first uses of nicotinic acid as a drug to change blood fat levels
date back to the mid-50s, however it was used in a limited way due to the side effects, in particular skin reddening.
It is believed that the redness caused by nicotinic acid is due to the release of a substance, the "prostaglandin D2" (PGD2), from the skin cells that causes a dilation of the blood vessels of the skin. Laropiprant blocks the receptors to which PGD2 normally attaches. With the receptors blocked, PGD2 is unable to dilate the vessels in the skin and this reduces the frequency and intensity of redness.
The Tredaptive tablet consists of a layer of laropiprant and a layer of nicotinic acid. After the intake, the laropiprant is first released into the blood, blocking the PGD2 receptors. Nicotinic acid is released more slowly from the other layer and its function is to modify fats.
What studies have been performed on Tredaptive?
The effects of Tredaptive were first tested in experimental models before being studied in humans.
Tredaptive has been the subject of four main studies conducted in patients with hypercholesterolemia or mixed dyslipidemia.
Two studies have examined the effectiveness of Tredaptive in modifying blood fat levels. The first study compared the effectiveness of Tredaptive with that of nicotinic acid alone or a placebo (a dummy treatment) in reducing LDL cholesterol levels on a total of 1613 patients. The study also examined the symptoms of redness through a specially crafted questionnaire.
The second study compared the combination of Tredaptive and simvastatin (a statin) with Tredaptive alone or simvastatin alone with 1398 patients. The main measure of effectiveness was the change in blood LDL cholesterol levels after 12 weeks.
The third and fourth studies examined the effectiveness of laropiprant in reducing the redness caused by nicotinic acid on a total of 2349 patients treated with Tredaptive or nicotinic acid. The redness was measured by a questionnaire on the symptoms of redness.
What benefit has Tredaptive shown during the studies?
Tredaptive was effective in reducing blood LDL cholesterol levels. In the first study, LDL cholesterol levels were reduced by 19% in patients treated with Tredaptive compared to 1% in patients treated with placebo. The second study showed that LDL cholesterol levels were further lowered if Tredaptive was taken in combination with simvastatin (48% reduction), compared to Tredaptive (17% reduction) or simvastatin (37% reduction) taken alone.
The addition of laropiprant to nicotinic acid reduced the symptoms of redness induced by nicotinic acid. In the first and third studies there were fewer reports of moderate, severe or extreme redness in patients treated with Tredaptive compared to patients treated with nicotinic acid alone. In the fourth study, redness appeared for less days in patients treated with Tredaptive than in patients treated only with nicotinic acid.
What is the risk associated with Tredaptive?
The most common side effect associated with Tredaptive (ie that seen in more than 1 in 10 patients) is redness. For the full list of all side effects reported with Tredaptive, see the Package Leaflet.
Tredaptive should not be used in patients who may be hypersensitive (allergic) to nicotinic acid, laropiprant or any of the other ingredients. It should also not be used in patients with liver problems, active stomach ulcers or arterial bleeding.
Why has Tredaptive been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that the benefits of Tredaptive outweigh the risks for the treatment of dyslipidemia, particularly in patients with combined mixed dyslipidaemia and in patients with primary hypercholesterolemia, and recommended the release of marketing authorization for Tredaptive.
Other information on Tredaptive:
On 3 July 2008, the European Commission issued a marketing authorization for Tredaptive, valid throughout the European Union, to Merck Sharp & Dohme Ltd.
The full EPAR for Tredaptive can be found here.
Last update of this summary: 05-2008.
