ZETIA ® is a drug based on Ezetimibe
THERAPEUTIC GROUP: Hypolipidemics - Ezetimibe
Indications ZETIA ® Ezetimibe
ZETIA ® is useful in the treatment of primary hypercholesterolemia, including heterozygous familial hypercholesterolemia, in case of failure of dietary therapy and other non-pharmacological measures.
Ezetimibe should be used as a pharmacological therapeutic choice in case of reduced tolerance or therapeutic failure of statins.
The combined statin-ezetimibe therapy, on the other hand, can be used successfully in case of homozygous familial hypercholesterolemia.
ZETIA ® can be used as an adjunct to the diet in patients with homozygous familial sitosterolemia.
Mechanism of action ZETIA ® Ezetimibe
Following oral administration, the ezetimibe contained in ZETIA ® is rapidly absorbed in the gastrointestinal tract and metabolized - both in the small intestine and in the liver - into ezetimibe-glucoronide, which preserves the biological functionality of the drug. Through an enterohepatic cycle, the active principle is excreted via the bile, reaching the intestine again. Here, at the level of the brush border, it inhibits the cholesterol transporter (NPC1L1), effectively preventing the uptake of cholesterol and sterols. natural ingredients taken with the diet.
After a half-life of approximately 22 hours, both ezetimibe and ezetimibe-glucuronide - which represents over 80% of the total dose of the active substance - are eliminated predominantly in the urine.
The reduction of LDL cholesterol induced by therapy with ezetimibe would be the basis of the therapeutic and preventive properties against cardiovascular diseases, although to date there are still no certain experimental data that attest, for example, the efficacy of the drug in the reduction of atherosclerotic plaques (very important risk factor).
Studies carried out and clinical efficacy
THE EFFECTIVENESS OF EZETIMIBE
Ann Pharmacother. 2003 Jun; 37: 839-48.
Ezetimibe for management of hypercholesterolemia.
Mauro VF, Tuckerman CE.
Ezetimibe, which entered common clinical practice only in 2002, has proved particularly effective in the treatment of hypercholesterolemia. A "careful examination of the scientific literature has allowed us to observe how this drug alone can reduce plasma levels of LDL cholesterol by about 18%, triglycerides by 5% and increase HDL cholesterol by approximately 3%. "potentiating action on the efficacy of statins, so as to increase their cholesterol-lowering effect by about 15 - 20%."
2. DISCUSSED EFFECTIVENESS OF EZETIMIBE IN THE PREVENTION OF DISEASES
CARDIOVASCULAR
Nutr Metab Cardiovasc Dis. 2010 Jun 2. [Epub ahead of print]
The role of ezetimibe in the prevention of cardiovascular disease: Where do we stand after ARBITER 6-HALTS.
Howard WJ.
Although the lipid-lowering effect of ezetimibe is known and well established, its potential protective effect against cardiovascular diseases still seems unclear. Indeed, it seems that ezetimibe can sustain this protective effect only when administered in combination therapy with statins or with drugs capable of promoting a greater increase in HDL cholesterol.
3. THE ABSENCE OF PLEIOTROPIC EFFECTS OF EZETIMIBE
Eur J Pharmacol. 2010 May 10; 633 (1-3): 62-70. Epub 2010 Feb 10.
Pleiotropic effects of ezetimibe: do they really exist?
Kalogirou M, Tsimihodimos V, Elisaf M.
Most lipid-lowering drugs (such as statins, fibrates, etc.) are characterized by the presence of secondary effects other than the simple lipid-lowering effect, which often contribute significantly to the reduction of cardiovascular risk. Unfortunately, ezetimibe appears to be provided exclusively with a cholesterol-lowering metabolic effect, which alone does not appear to significantly protect against cardiovascular diseases.
Method of use and dosage
ZETIA ® 10mg tablets of ezetimibe: the initial treatment involves the administration of one tablet per day, taken with water regardless of meals (which do not seem to affect the normal pharmacokinetic properties of the active ingredient).
As with all lipid-lowering therapies, it is advisable to start the therapeutic protocol by associating it with a hypolipidic dietary regimen, and to opt for drug therapy only in case of failure of the behavioral treatment (diet and physical activity).
When given concomitantly with statins, the dosage of ZETIA ® may need to be adjusted
Warnings ZETIA ® Ezetimibe
Before starting the drug treatment, it is advisable to follow healthy habits of life and a low-fat diet for at least 12 weeks. If the results obtained were unsatisfactory and far from the therapeutic target, the use of the drug is fully justified.
Before and during treatment with ZETIA ®, especially when combined with statins, it is advisable to monitor the blood levels of transaminases, in order to reduce any risk of liver disease. At the same time, it is necessary to control plasma concentrations of creatine phosphokinase, in order to reduce any pathological processes affecting the skeletal muscle. Combined therapy should therefore be suspended in the event of an increase in transaminases of at least 3 times the normal range, or in the event of an increase in plasma creatine phosphokinase levels accompanied by muscle pain, widespread myalgia, tiredness and fatigue.
Furthermore, ZETIA ® should be administered with particular caution in case of impaired renal function and diseases affecting the gallbladder and biliary tract (such as cholelithiasis).
Among the excipients of ZETIA ® there is lactose, potentially responsible for adverse gastrointestinal reactions in patients suffering from glucose / galactose malabsorption syndrome, and in case of lactase enzyme deficiency.
Although the drug does not appear directly capable of altering the patient's normal reactive and perceptive abilities, side effects such as dizziness and vertigo could make it dangerous to use machinery or drive vehicles.
IN ANY CASE, BEFORE TAKING ZETIA ® Ezetimibe - YOU MUST BE PRESCRIBED AND CHECKED BY YOUR DOCTOR.
PREGNANCY AND BREASTFEEDING
Clinical trials concerning the use of ezetimibe in pregnancy and lactation are non-existent, while studies conducted on animals have shown the absence of toxic or mutagenic effects on the fetus. Therefore, it is preferable to avoid taking this drug during the entire pregnancy period and the subsequent lactation phase.
Interactions
The absence of hepatic metabolism involving cytochrome P450 allows ezetimibe to significantly reduce all possible drug interactions, some of which are potentially dangerous.
In fact, ezetemibe does not seem to alter the pharmacokinetic and functional properties of oral anticoagulants, keeping the prothrombin time unchanged.
However, the concomitant use of fibrates, following an "increased secretion of cholesterol in the bile, could lead to an increased risk of cholelithiasis, which would justify the suspension of therapy.
Antacids and cholestyramine appear to reduce the absorption rate of ezetemibe, while cyclosporine would determine a significant increase in drug exposure; in these cases it would therefore be advisable to administer ZETIA ® with great caution, adjusting the dosage if necessary.
The therapeutic synergy observed with statins is very important, so much so that this combined therapy is used with great success in common clinical practice.
Contraindications ZETIA ® Ezetimibe
ZETIA ® is contraindicated in case of liver disease or high blood transaminase values, as well as in the presence of hypersensitivity to one of its components.
Undesirable Effects - Side Effects
Although side effects appear transient and clinically insignificant, it should be reiterated that their incidence tends to increase when ezetimibe is administered concomitantly with a statin.
The most observed adverse reactions include headache, myalgia, abdominal pain, diarrhea and persistent fatigue, sometimes accompanied by an increase in blood transaminase values, especially if ZETIA is combined with statins.
Other more serious side effects, such as dyspnoea, myopathies, hypersensitivity and asthenia, appear statistically insignificant.
Note
ZETIA ® can only be sold under medical prescription.
The information on ZETIA ® Ezetimibe published on this page may be out of date or incomplete. For a correct use of this information, see the Disclaimer and useful information page.
