ZETIA ® is a drug based on Ezetimibe
THERAPEUTIC GROUP: Ipolipemizzanti - Ezetimibe
IndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects
Directions ZETIA ® Ezetimibe
ZETIA ® is useful in the treatment of primary hypercholesterolemia, including the heterozygous family, in case of failure of diet therapy and other non-pharmacological measures.
The use of ezetimibe should be used, as a pharmacological therapeutic choice, in case of reduced tolerance or therapeutic failure of statins.
The statin-ezetimibe combination therapy can instead be used successfully in cases of homozygous familial hypercholesterolemia.
ZETIA ® can be used in addition to diet in patients with homozygous familial sitosterolemia.
Mechanism of action ZETIA ® Ezetimibe
The ezetimibe contained in ZETIA ® following oral administration is rapidly absorbed at the gastro-intestinal level and metabolized - both in the small intestine and in the liver - in 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 brush edge level, it inhibits the cholesterol transporter (NPC1L1), effectively preventing the uptake of cholesterol and natural sterols taken with the diet.
After a half-life of approximately 22 hours, both ezetimibe and ezetimibe-glucoronide - which accounts for over 80% of the total active principle dose - are eliminated mainly through the urine.
The reduction of LDL cholesterol induced by ezetimibe therapy would be the basis of the therapeutic and preventive properties against cardiovascular diseases, although to date there is still a lack of certain experimental data that attest, for example, to 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
Ezetimibe, which entered common clinical practice only since 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 can alone reduce plasma LDL cholesterol levels by about 18%, triglycerides by 5% and increase HDL cholesterol by approximately 3%. Very interesting is instead the action of strengthening the effectiveness of statins, so as to increase the cholesterol lowering effect by about 15 - 20%.
2. DISCUSSED EFFECTIVENESS OF EZETIMIBE IN THE PREVENTION OF PATHOLOGIES
Although the lipid-lowering effect of ezetimibe is known and well established, its potential protective effect against cardiovascular diseases still seems unclear. Indeed, it appears that ezetimibe can support this protective effect only when given 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
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. Ezetimibe, unfortunately, seems to be provided exclusively with a cholesterol-lowering metabolic effect, which alone does not appear to protect significantly from cardiovascular diseases.
Method of use and dosage
ZETIA ® 10mg tablets of ezetimibe: the initial treatment involves the administration of one tablet a day, taken with water independently of the meals (which do not seem to influence the normal pharmacokinetic properties of the active ingredient).
As with all lipid-lowering therapies, it is good to begin the therapeutic protocol by associating it with a hypolipid dietary regimen, and opt for drug therapy only in the event of failure of behavioral treatment (diet and physical activity).
When co-administered with statins, the dosage of ZETIA ® may need to be adjusted
Warnings ZETIA ® Ezetimibe
Before starting the pharmacological treatment, healthy lifestyle habits and a hypolipidic diet should be followed 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 associated with statins, it is appropriate to monitor blood transaminase levels, in order to reduce any risk of liver disease. At the same time, it is necessary to control the plasma concentrations of creatine phosphokinase, in order to reduce any pathological processes affecting the skeletal muscle. The combined therapy should therefore be suspended in the event of increased transaminases of at least 3 times the normal range, or in the event of an increase in the plasma levels of creatine phosphokinase accompanied by muscle pain, widespread myalgia, tiredness and fatigue.
Furthermore, ZETIA ® should be administered with particular caution in the case of reduced renal function and diseases of the gallbladder and biliary tract (such as cholelithiasis).
Among the excipients of ZETIA ® is lactose, potentially responsible for adverse reactions in the gastro-intestinal tract in patients with glucose / galactose malabsorption syndrome, and in the case of lactase enzyme deficiency.
Although the drug does not appear to be able to directly alter the patient's normal reactive and perceptive capacities, side effects such as dizziness and vertigo could make the use of machinery or driving vehicles dangerous.
IN ANY CASE, BEFORE TAKING ZETIA ® Ezetimibe - THE REQUIREMENT AND CHECK OF YOUR DOCTOR IS NECESSARY.
PREGNANCY AND BREASTFEEDING
The clinical trial concerning the use of ezetimibe in pregnancy and lactation is non-existent, while animal studies have shown the absence of toxic or mutagenic effects on the fetus. Therefore, it is preferable to avoid taking this drug during the entire period of pregnancy and the subsequent stage of breastfeeding.
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, maintaining 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, whereas ciclosporin would result in a significant increase in drug exposure; in these cases it would therefore be advisable to administer ZETIA ® with great caution, possibly adjusting the dosage.
Very important is the therapeutic synergy observed with statins, so much so that this combined therapy is used with great success in the common clinical practice.
Contraindications ZETIA ® Ezetimibe
ZETIA ® is contraindicated in case of liver disease or elevated blood transaminase values, as well as in the presence of hypersensitivity to one of its components.
Undesirable effects - Side effects
Although the side effects appear to be 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 levels of transaminases, especially if ZETIA is associated with statins.
Other more serious side effects, such as dyspnea, myopathies, hypersensitivity and asthenia, appear statistically insignificant.
Note
ZETIA ® is salable only under medical prescription.
