'Tredaptive'® (Nicotinic Acid/Laropiprant) Authorised In The European Union: New Lipid-Modifying Therapy To Treat LDL-C, HDL-C And Triglycerides
'Tredaptive' combines nicotinic acid (niacin) and laropiprant, a novel flushing pathway inhibitor. Clinical studies have shown nicotinic acid/laropiprant to reduce LDL- cholesterol (LDL-C, or "bad" cholesterol) levels, raise HDL-cholesterol (HDL-C, or "good" cholesterol) and decrease triglycerides (a type of fat in the blood).1 High LDL-C, low HDL-C and elevated triglycerides are risk factors associated with heart attacks and strokes.2,3,4
Professor Ian Young, Consultant in Clinical Biochemistry, Queen's University, Belfast comments, "Lowering LDL-C is the cornerstone of lipid management but a number of studies indicate triglycerides and HDL also have a key role in cardiovascular disease risk. The JBS 2 guidelines recommend that HDL-C and triglyceride values should also be considered in overall lipid management and other lipid lowering drugs should be considered in addition to a statin if cholesterol targets have not been achieved or other lipid parameters need to be addressed. Nicotinic acid/laropiprant can address these key cardiovascular risk factors and therefore could be an important treatment option in combination with statins, when statin monotherapy alone is inadequate, particularly for high risk patients."
Nicotinic acid/laropiprant is indicated for the treatment of dyslipidaemia, particularly in patients with combined mixed dyslipidaemia (characterised by elevated levels of LDL-C and triglycerides and low HDL-C) and in patients with primary hypercholesterolaemia (heterozygous familial and non-familial).1
Nicotinic acid/laropiprant should be used in patients in combination with statins, when the cholesterol lowering effects of statin monotherapy is inadequate. It can be used as monotherapy only in patients in whom statins are considered inappropriate or not tolerated. Diet and other non-pharmacological treatments (e.g. exercise, weight reduction) should be continued during therapy.1
"The approval of nicotinic acid/laropiprant in the European Union further reinforces our long- standing commitment to the cardiovascular area by bringing novel and innovative therapies to patients. The product provides comprehensive management of all three lipid parameters - LDL-C, HDL-C and triglycerides - for many patients," said Stefan Oschmann, President, MSD, Europe, Middle East, Africa and Canada.
Nicotinic acid/laropiprant provided significant improvements in LDL-C, HDL-C and triglycerides
When added to ongoing statin therapy or alone, nicotinic acid/laropiprant 2000 mg/40 mg provided significant improvements in LDL-C, HDL-C and triglycerides when administered for a 24 week period. Nicotinic acid/laropiprant 1000 mg/20 mg daily tablet was initiated at the study start; at week 4 the daily dose was advanced to the maintenance dose of 2000 mg/40 mg (2 x 1000 mg/20 mg tablets) through the remaining 20 weeks of the study. Across weeks 12 to 24 of the study, placebo adjusted results showed that nicotinic acid/laropiprant significantly reduced LDL-C levels (-18 percent), increased HDL-C levels (20 percent) and reduced triglyceride levels (-25 percent).1
When nicotinic acid/laropiprant was co-administered with simvastatin (data pooled across 1000 mg/20 mg or 2000 mg/40 mg doses) LDL-C was reduced by 48 percent, HDL-C increased by 28 percent and triglycerides were reduced by 33 percent following 12 weeks of treatment.1
Flushing with nicotinic acid/laropiprant (modified-release tablet) was significantly less than with nicotinic acid (prolonged release formulation)
In clinical studies, patients taking nicotinic acid/laropiprant (modified-release tablet) experienced significantly less moderate-to-extreme flushing than with nicotinic acid (prolonged release formulation). Patients were initiated on either 1000 mg/20 mg of nicotinic acid/laropiprant or 1000 mg of nicotinic acid or placebo. After 4 weeks, patients were advanced to 2000 mg/40 mg or 2000 mg respectively.1
In patients who continued treatment with nicotinic acid/laropiprant after the dose advancement the weekly frequency of moderate or greater flushing decreased and approached that of patients receiving placebo. In patients treated with nicotinic acid alone, the weekly flushing frequency remained constant (after week 6).1
Fewer discontinuation rates due to flushing with nicotinic acid/laropiprant
In a pool of four active- or placebo-controlled clinical trials of more than 4,700 patients the percentage of patients taking nicotinic acid/laropiprant who discontinued due to any flushing related symptom was 7.2 percent compared to 16.6 percent for the pooled nicotinic acid (prolonged release formulation) alone groups.5
Important information about nicotinic acid/laropiprant
Nicotinic acid/laropiprant is generally well tolerated.5 Flushing is the most common side-effect and is most prominent in the head, neck and upper torso. Additional common clinical adverse reactions (≥ 1 percent to < 10 percent) reported by the investigators as possibly, probably, or definitely related to the product in ≥ 1 percent of patients treated with nicotinic acid acid/laropiprant alone or co-administered with a statin for up to one year included elevations in ALT or AST (consecutive ≥ 3X ULN), fasting glucose, uric acid, dizziness, headache, paraesthesia (a feeling of numbness, tingling, pricking, or burning of the skin), diarrhoea, dyspepsia, nausea, vomiting, erythema (redness of the skin), pruritus (itching), rash, urticaria and feeling hot.1
Nicotinic acid medicinal products have been associated with increases in fasting blood glucose levels.1,5 Diabetic or potentially diabetic patients should be observed closely. Adjustment of diet and/or hypoglycaemic therapy may be necessary.1
As with other nicotinic acid products, nicotinic acid/laropiprant is contra-indicated in patients with significant or unexplained hepatic dysfunction and should be used in caution in those with renal impairment.1
Notes
Impact of three major lipids on cardiovascular risk factors
Cardiovascular disease (CVD) is a general term referring to diseases that affect the heart or blood vessels. Coronary heart disease (CHD), also known as coronary artery disease (CAD), is one of the most common forms of CVD and is the leading cause of death globally.6 Major risk factors for CVD include abnormal blood lipids, meaning not only high LDL-C but also high levels of triglycerides and low levels of HDL-C.7,8
CVD is the main cause of death in Europe, accounting for over 4.3 million deaths (48% of all mortality).9 It is also the UK's number one killer with more than one in three people dying from a heart attack or stroke.10 Coronary Heart Disease by itself is the most common cause of death in the U.K. accounting for 101,000 deaths per year.10
About Merck Sharp & Dohme
Merck Sharp & Dohme Limited (MSD) is the UK subsidiary of Merck & Co., Inc., of Whitehouse Station, New Jersey, USA, a leading research-based pharmaceutical company that discovers, develops, manufactures and markets a wide range of innovative pharmaceutical products to improve human health.
Forward-Looking Statement
This press release contains "forward-looking statements" about product development, product potential or about financial performance based on current expectations of the management of Merck & Co., Inc. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck & Co., Inc. undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
References
1. Summary of Product Characteristics for 'Tredaptive'
2. Kannel WB. Status of risk factors and their consideration in antihypertensive therapy. Am J Cardiol. 1987;59:80A-90A
3. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497
4. Nordestgaard BG, Benn M, Schnohr P et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298:299-308
5. McKenney J, Bays H, Koren M et al. Safety profile of extended-release niacin/laropiprant in patients with dyslipidemia. Poster presented at American College of Cardiology, 57th Annual Scientific Session, March 29-April 1 2008, Chicago
6. World Health Organization. The Top 10 causes of death factsheet. February 2007
7. Heart UK, 'Risk factors for CHD' factsheet, http://www.heartuk.org.uk/new/downloads/factsheets/I-Risk_Factors.pdf [Accessed on 03.07.08]
8. Department of Health, Health Survey for England 2003, Volume 2, 'Risk factors for cardiovascular disease
9. European Heart Network. European Cardiovascular disease statistics 2008 edition
10. Allender S, Peto V, Scarborough P, et al. Coronary heart disease statistics 2007, Chapter 1. British Heart Foundation, London
Source:
Merck Sharp & Dohme Limited
http://www.msd-uk.co.uk
"Tredaptive '? (acid nicotinic / Laropiprant) autorizate în Uniunea Europeanã: New lipidic-Modificarea Tratamentul pentru tratarea LDL-C, HDL-C ºi trigliceridelor - 'Tredaptive'® (Nicotinic Acid/Laropiprant) Authorised In The European Union: New Lipid-Modifying Therapy To Treat LDL-C, HDL-C And Triglycerides - articole medicale engleza - startsanatate