Ezetimibe Domina   (Tablets)

 

COMPOSITION:
Each tablet contains 10mg Ezetimibe.

MECHANISM OF ACTION:
Ezetimibe is in a new class of lipid lowering compounds that selectively inhibit the intestinal absorption of cholesterol and related plant sterols. The cholesterol content of the liver is derived predominately from three sources:

  • The live can stabilize cholesterol.
  • Take up cholesterol from the blood from circulating lipoproteins.
  • Take up cholesterol absorbed by the small intestine. Intestinal cholesterol is derived primarily from cholesterol secreted in the pile and from dietary cholesterol.   

Ezetimibe Domina has a mechanism of action that differs from other classes of cholesterol reducing compounds. Ezetimibe Domina does not inhibit cholesterol synthesis in the liver, or increase bile acid excretion, but it localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood, this distinct mechanism is complementary to that of statins.
Ezetimibe either as a monotherapy or co-administered with a statin significantly reduces total-C, LDL-C, Apo B, and TG, and increases HDL-C in patients with hypercholesterolemia.

INDICATIONS:
Primary hypercholesterolaemia:

  • Ezetimibe Domina monotherapy is indicated as adjunctive therapy to diet for use in patients with primary (heterozygous familial and non familial) hypercholesterolaemia in whom a statin is considered inappropriate or is not tolerated.
  • Ezetimibe Domina, co-administered with a statin is indicated as adjunctive therapy to diet for use in patients with primary (heterozygous familial and non familial) hypercholesterolaemia who are not appropriately controlled with a statin alone.

Homozygous Familial Hypercholesterolemia (HoFH):

  • Ezetimibe Domina co-administered with a statin, is indicated as adjunctive therapy to diet for use in patients with HoFH.

Patients may also receive adjunctive therapy (e.g. LDL apheresis).
Homozygous sitosterolaemia (phytosterolaemia):

  • Ezetimibe Domina is indicated as adjunctive therapy to diet for the reduction of elevated sitoserol and campesterol levels.

DOSAGE:
Ezetimibe Domina can be administered at any time of the day, with or without food.
The recommended dose is one Ezetimibe Domina 10mg tablet daily.
When Ezetimibe Domina is added to a statin, either indicated usual initial dose of that particular statin or the already established higher statin dose should be continued. In this setting, the dosage instructions for that particular statin should be consulted
Co-administration with bile acid sequestrants: Dosing of Ezetimibe Domina should occur either ³2 hours before or ³4 hours after administration of a bile acid sequestrant.
No dosage adjustment is required in patients with mild hepatic insufficiency, patients with renal insufficiency, or for elderly Patients.
Ezetimibe Domina is not recommended for use in children below age of 10 years due to insufficient data on safety and efficacy.

SIDE EFFECTS:
Ezetimibe Domina side effects are generally mild and transient.
Ezetimibe administered alone: Headache, abdominal pain and diarrhea.
Ezetimibe co-administered with a statin: Headache, fatigue, abdominal pain, constipation, diarrhea, flatulence, nausea, myalgia.
Ezetimibe co-administered with fenofibrate: Abdominal pain.
Other side effects (rare): Angioedema, rash, arthralgia, oesophagitis. 

CONTRAINDICATIONS:
Hypersensitivity to the active substance or to any of the excipients. When Ezetimibe Domina is co-administered with a statin, please refer to the special precaution for that particular medicinal product. Therapy with ezetimibe co-administered with a statin is contraindicated during pregnancy and lactation. Ezetimibe co-administered with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases.

DRUG INTERACTIONS:
Concomitant cholestyramine administration decreased the mean area under the curve of (ezetimibe + ezetimibe glucuronide) approximately 55%.
Plasma Concentrations of ezetimibe increased by ciclosporin co-administration.
Concomitant fenofibrate or gemfibrozil administration increased total ezetimibe concentrations approximately 1.5- and 1.7-fold respectively, however these increases are not considered clinically significant.

PRECAUTIONS:
Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic insufficiency, ezetimibe is not recommended in these patients.
In controlled co-administration trials in patients receiving ezetimibe with a statin, consecutive transaminase elevations (≥3X the upper limit of normal) have been observed. When Ezetimibe Domina is co-administered with a statin, liver function tests should be performed at initiation of therapy and according to the recommendations of the Statin.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The product is not expected to affect the ability to drive or use machines.

USE IN PREGNANCY OR LACTATION:
Category C, the product should be given to pregnant women only if clearly necessary, and if patient becomes pregnant while taking this drug, ezetimibe should be discontinued immediately.
The product should not be used during lactation.

PHARMACOKINETIC PROPERTIES:
Absorption: After oral administration, ezetimibe is rapidly absorbed and extensively conjugated to a pharmacologically active phenolic glucuronide (ezetimibe–glucuronide). Mean maximum plasma concentrations (Cmax) occur within 1 to 2 hours for ezetimibe–glucuronide and 4 to 12 hours for ezetimibe.
Concomitant food administration (high fat or non fat meals) has no effect on the oral bioavailability of ezetimibe.
Distribution: Ezetimibe and ezetimibe–glucuronide are bound 99.7% and 88-92% to human plasma proteins, respectively.
Biotransformation: Ezetimibe is metabolized primarily in the small intestine and liver via glucuronide conjugation with subsequent biliary excretion. Ezetimibe and ezetimibe–glucuronide are the major drug derived compound detected in plasma. The half-life for ezetimibe and ezetimibe – glucuronide is approximately 22 hours.

PRESENTATION:
Carton pack containing 3 blisters of 10 tablets in each, with leaflet

 

 

 
 
 

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