Policosanol - physician information

A new safe and effective lipid-lowing agent. In human studies over 3 years indicated no liver toxicity or myopathy. (Am Heart J 2002;143:356-65)

Equally effective as Mevacor (Lovastatin) (Int J Clin Pharmacol Res 1999;19(4):117-27)

More effective than Zocor (simvastatin) (Rev Med Chil 1999 Mar;127(3):286-94)

More favorable results than Pravachol (pravastatin) (Int J Clin Pharmacol Res 1999;19(4):105-16)

Reduces Platelet aggregation (Int J Tissue React 1998;20(4):119-24)

Reduces Platelet aggregation equal to 100 mg ASA (Pharmacol Res 1997 Oct;36(4);293-7)

No teratogenic effects in animal studies (Teratog Carcinog Mutagen 1998;18(1):1-7)

American Heart Journal

February 2002 Volume 143 Number 2

Policosanol: Clinical pharmacology and therapeutic significance of a new lipid-lowing agent

Authors: Ionana Gouni-Berthold, MD

Heiner Berthold, MD, PhD

University of Bon (Germany)

Center for cardiovascular Diseases

Background: Policosanol is a mixture of higher primary aliphatic alcohols isolated from sugar cane wax, whose main component is octacosanol. The mixture has been shown to lower cholesterol in animal models, healthy volunteers and patients with type II hypercholesterolemia.

Methods: We reviewed the literature on placebo-controlled lipid-lowering studies using policosanol published in peer-reviewed journals as well as studies investigating its mechanism of action and its clinical pharmacology.

Results: At doses of 10 to 20 mg per day, policosanol

- lowers total cholesterol by 17 to 21%

- lowers low-density lipoprotein (LDL) cholesterol by 21 to 29%

- raises high-density lipoprotein cholesterol by 8 to 15%

Because higher doses have not been tested up to now, it cannot be excluded that effectiveness may be even greater. Daily doses of 10 mg of policosanol have been shown to be equally effective in lowering total or LDL cholesterol as the same dose of simvastatin (Zocor) or pravastatin (Pravachol). Triglyceride levels are not influenced by policosanol. At dosages of up to 20 mg per day, policosanol is safe and well tolerated, as studies of > 3 years of therapy indicate. There is evidence from in vitro studies that policosanol may inhibit hepatic cholesterol synthesis at a step before mevalonate generation, but direct inhibition of the hydroxy-methyglutaryl-coenzyme A reductase is unlikely. Animal studies suggest that LDL catabolism may be enhanced, possibly through receptor-mediated mechanisms, but the precise mechanism of action is not understood yet. Policosanol has additional beneficial properties such as effects on smooth muscle proliferation, platelet aggregation, and LDL peroxidation. Data on efficacy determined by clinical end points such as rates of cardiac events or cardiac mortality are lacking.

Conclusions: Policosanol seems to be a very promising phytochemical alternative to classic lipid-lowering agents such as the statins and deserves further evaluation. (Am Heart J 2002;143:356-65)

Additional Information 8/02

Dr. David Martin, Pharm.D., FACN CNS

Meta-analysis of the NCEP studies have shown that for every 10 percentage point of cholesterol lowering CHD mortality was decreased by 13% and total mortality by 10%. The NHANES III survey estimated that 5.5 million Americans with CHD should be treated with lipid-lowering medication. Only a small portion actually receive treatment. Many patients are reluctant to be treated with chemically derived drugs, especially for primary prevention. Now, with the availability of policosanol in the US and >25 other countries, there is a safe, naturally derived option to cholesterol-lowering drugs.

Efficacy and safety has been studied in >3000 patients and in over 60 clinical trials. Numerous studies are in progress around the world including our own.

Pharmacokinetics: Policosanol absorption from the GI tract is low with no competitive or noncompetitive inhibition of HMG-CoA suggesting local effects and in part increased receptor-mediated uptake of LDL-C by the liver resulting in a product with no known toxicity. Animal studies showed absorption between 10 & 35% and bioavailability between 5 & 12%. Intravenous administration revealed a terminal half-life of 1 to 2 hours. Several animal studies, in large doses -- 500 mg/kg -- showed no carcinogenicity, mutagenic or reproductive toxicity. In healthy humans single doses of 1000 mg were administered without adverse drug reactions.

Animal and a few human studies have demonstrated reduction of atherosclerotic lesions, decrease neointimal smooth muscle cell proliferation, lipoprotein oxidation, foam cell formation, thromboxane B2 and platelet aggregation with an increase in prostacyclin levels. Animal studies have show prevention of cerebral ischemia induced models.

Drug Interactions: Data is available from long-term studies in humans with co-administration of policosanol with calcium channel blockers, angiotensin-converting enzyme inhibitors, beta blockers, diuretics, nitrates, nonsteroidal anti-inflammatory drugs, anxiolytics, antidepressants, neuroleptics, oral hypoglycemics, digoxin, thyroid hormones and antiulcer drugs as being safe; formal drug interaction studies in humans are now in progress.

Although studies demonstrate that policosanol reduces platelet aggregation equal to 100 mg of aspirin without affecting coagulation time or INR if on Coumadin, consider continuing 81 mg aspirin for reduction of C-Reactive Protein (CRP). No studies are available with other antiplatelet or anticoagulant drugs eg clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox) other LMWH, heparin and Coumadin. There are no known interactions with food.

Policosanol refers to a mixture of 24-34 carbon aliphatic alcohols comprised primarily of octacosanol. Avoid Octacosanol only products. Research to date has been limited to policosanol from sugar cane wax. Until more is known avoid products using policosanol from bees wax.

Dosage & Administration: Recommended dosage is 20 mg a bedtime for 3 months repeat lipid profile and compare to base-line lipid panel for dosage adjustment. If the patient is not taking CoQ10 it is recommended to take 15 mg CoQ10 with each 10 mg policosanol. Dosage range in studies ranged from 5 mg once a day with evening meal to 20 mg q d. Studies of 40 to 80 mg q d have shown dose-dependent efficacy but improvement was not linear.

Although no teratogenic effects have been found in animals policosanol is contraindicated during pregnancy. It is not known whether policosanol or its metabolites pass into human milk; therefore therapy must be discontinued during lactation.

There has been no experience in children and therefore use or dosages cannot be recommended.

Liver function - no dose reduction is recommended.

Renal function - no studies have been published

Pharmacogenonmic studies are in progress. Metabolism variations in different

ethnic groups is currently unknown.

Monitoring: Base-line lipid panel is recommended. After 3-months on 20 mg a day recheck lipid panel for dosage adjustment based on LDL-C effect.

Monitoring liver panel is not necessary for policosanol therapy but patients on any drug therapy may benefit from periodic comprehensive metabolic, lipid panel and hematological evaluations.

Policosanol tends to increase HDL greater than equivalent doses of statins or therapy with fibrates, but outcome efficacy should focus on LDL-C effects. In evaluating total cholesterol it is important to consider that there is a LDL and a significant concurrent increase in HDL making total cholesterol a weak indicator of therapy. Effects on particle size, ie HDL - LDL GGE subsets are unknown at this time. We are monitoring patients with base-line lipid fractionation with repeated Berkeley Heart Lab studies for changes in particle size, Lp(a), fibrinogen and homocysteine. In clinical trials triglyceride levels during therapy were variable (+17% to -34%).

Patients that have been taking statins, we recommend a base-line liver panel and CPK -- if the patient reports muscle pain or weakness -- along with the base-line lipid panel.

In clinical trials, the most frequent adverse effects reported were weight loss (1.8%), polyuria (0.7%) and headache (0.6%) with no biochemical, organ function or lab interference.

Studies in NIDDM with hypercholesterolemia treatment with policosanol produced pronounced effect on reducing LDL and increasing HDL but T/G, glucose levels and hemoglobin A1c values remained unchanged.

Summary: Policosanol appears to be an excellent alternative for patients requesting a natural product for prevention or treatment of atherosclerotic disease. Patients should be advised that policosanol is part of therir overall medical treatment and the therapy should be monitored by a physician.

How Supplied: Policosanol 10 mg (60 tablets)

Policosanol 10 mg with CoQ10 15 mg (60 tablets)

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