Ezalo Composite Pack
Ezalo Composite Pack Uses, Dosage, Side Effects, Food Interaction and all others data.
Ezetimibe localises at the brush border of the small intestine and inhibits absorption of cholesterol via the sterol transporter, Niemann-Pick C1-Like1 (NPC1L1). This results in decreased delivery of cholesterol to the liver, reduction of hepatic cholesterol stores and increased clearance of cholesterol from the blood.
Ezetimibe was shown to reduce the levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG), and increase high-density lipoprotein cholesterol (HDL-C) in patients with hyperlipidemia. This therapeutic effect was more profound when ezetimibe was co-administered with a statin or fenofibrate compared to either treatment alone. In clinical trials involving patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia, a recommended therapeutic dose of ezetimibe was effective in reducing the LDL levels by 15-20% while increasing HDL-C by 2.5-5%.
The effects of increased exposure to ezetimibe secondary to moderate-severe hepatic impairment have not been assessed - patients meeting these criteria should avoid the use of ezetimibe. Post-marketing reports indicate the potential for myopathy and rhabdomyolysis in patients taking ezetimibe, and this risk appears to be exacerbated in patients concurrently receiving, or having recently received, statin therapy.
| Trade Name | Ezalo Composite Pack |
| Generic | ezetimibe + rosuvastatin calcium |
| Type | |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Australia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Primary Hypercholesterolemia: Ezetimibe co-administered with statin is used for adjunctive therapy to diet for use in patients with primary (heterozygous familial and non-familial) hypercholesterolemia who are not appropriately controlled with a statin alone.Ezetimibe monotherapy is used for adjunctive therapy to diet for use in patients with primary (heterozygous familial and non-familial) hypercholesterolemia in whom a statin is considered inappropriate or is not tolerated.
Prevention of Cardiovascular Events: Ezetimibe is used to reduce the risk of cardiovascular events in patients with coronary heart disease (CHD) and a history of acute coronary syndrome (ACS) when added to ongoing statin therapy or initiated concomitantly with a statin.
Homozygous Familial Hypercholesterolaemia (HoFH): Ezetimibe co-administered with a statin, is used for adjunctive therapy to diet for use in patients with HoFH. Patients may also receive adjunctive treatments (e.g., LDL apheresis).
Homozygous Sitosterolemia (Phytosterolemia): Ezetimibe is used for adjunctive therapy to diet for use in patients with homozygous familial sitosterolemia
Rosuvastatin is indicated in- Heterozygous Hypercholesterolemia (Familial and Non familial) Homozygous Hypercholesterolemia (Familial) Mixed Dyslipidemia (Fredrickson Type IIa and IIb) Primary prevention of cardiovascular diseaseEzalo Composite Pack is also used to associated treatment for these conditions: Elevated Blood Lipids, Elevated sitosterol and campesterol
How Ezalo Composite Pack works
Ezetimibe mediates its blood cholesterol-lowering effect via selectively inhibiting the absorption of cholesterol and phytosterol by the small intestine without altering the absorption of fat-soluble vitamins and nutrients. The primary target of ezetimibe is the cholesterol transport protein Niemann-Pick C1-Like 1 (NPC1L1) protein. NPC1L1 is expressed on enterocytes/gut lumen (apical) as well as the hepatobiliary (canalicular) interface and plays a role in facilitating internalization of free cholesterol into the enterocyte in conjunction with the adaptor protein 2 (AP2) complex and clathrin. Once cholesterol in the gut lumen or bile is incorporated into the cell membrane of enterocytes, it binds to the sterol-sensing domain of NPC1L1 and forms a NPC1L1/cholesterol complex. The complex is then internalized or endocytosed by joining to AP2 clathrin, forming a vesicle complex that is translocated for storage in the endocytic recycling compartment.
Ezetimibe does not require exocrine pancreatic function for its pharmacological activity; rather, it localizes and appears to act at the brush border of the small intestine. Ezetimibe selectively blocks the NPC1L1 protein in the jejunal brush border, reducing the uptake of intestinal lumen micelles into the enterocyte. Overall, ezetimibe causes a decrease in the delivery of intestinal cholesterol to the liver and reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood. While the full mechanism of action of ezetimibe in reducing the entry of cholesterol into both enterocytes and hepatocytes is not fully understood, one study proposed that ezetimibe prevents the NPC1L1/sterol complex from interacting with AP2 in clathrin coated vesicles and induces a conformational change in NPC1L1, rendering it incapable of binding to sterols. Another study suggested that ezetimibe disrupts the function of other protein complexes involved in regulating cholesterol uptake, including the CAV1–annexin 2 heterocomplex.
Dosage
Ezalo Composite Pack dosage
The recommended dose of Ezetimibe is 10 mg once daily. Ezetimibe can be administered with or without food.
Dose range: 5-40 mg once daily. Use 40 mg dose only for patients not reaching LDL-C goal with 20 mgHoFH: Starting dose 20 mg/day.Pediatric patients with HeFH: 5-10 mg/day for patients 8 to less than 10 years age, and 5-20 mg/day for patients 10 to 17 years of age.Pediatric patients with HoFH: 20 mg/day for patients 7 to 17 years of age. Rosuvastatin can be taken with or without food, at any time of day.Side Effects
Clinical studies of Ezetimibe (administered alone or with an HMG-CoA reductaseinhibitor) demonstrated that Ezetimibe was generally well tolerated. The overallincidence of adverse events reported with Ezetimibe was similar to that reported withplacebo, and the discontinuation rate due to adverse events was also similar for Ezetimibeand placebo.
Rosuvastatin is generally well tolerated. The most frequent adverse events thought to be related to Rosuvastatin were headache, myalgia, constipation, asthenia, abdominal pain and nausea.Toxicity
Oral LD50 and intraperitoneal LD50 in rat were >2000 mg/kg. Estimated oral LD50 values in mouse and dog are >5000 mg/kg and >3000 mg/kg, respectively. One case of accidental overdose occurred in clinical studies in one female patient with homozygous sitosterolemia receiving 120 mg/day for 28 days with no reported clinical or laboratory adverse events. In case of overdose, symptomatic treatment is recommended.
Precaution
Exclude or treat secondary causes of dyslipidaemia prior to initiating therapy. Renal and hepatic impairment. Pregnancy and lactation.
Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase with use of 40 mg dose, advanced age (>65 year), hypothyroidism, renal impairment and combination use with cyclosporine, lopinavir/ritonavir, atazanavir/ritonavir or certain other lipid-lowering drugs. Patients should be advised to promptly report unexplained muscle pain, tenderness or weakness. Rosuvastatin can be discontinued if signs or symptoms appear.Liver enzyme abnormalities and monitoring: Persistent elevations in hepatic transaminases can occur. Liver enzymes should be monitored before and during treatmentInteraction
Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in animals, Ezetimibe increased cholesterol in the gallbladder bile. Coadministration of Ezetimibe with fibrates is not therefore recommended until use in patients is studied.
Remarkable drug interactions of Rosuvastatin are- Cyclosporine: Combination increases Rosuvastatin exposure. Rosuvastatin dose should be limited to 5 mg once daily. Gemfibrosil: Combination should be avoided. If used together, Rosuvastatin dose should be limited to 10 mg once daily. Lopinavir/Ritonavir or atazanavir/ritonavir: Combination increases Rosuvastatin exposure. Rosuvastatin dose should be to 10 mg once daily. Coumarin anticoagulants: Combination prolongs international normalized ratio (INR). Stable INR should be achieved prior to starting Rosuvastatin. INR should be monitored frequently until stable upon initiation or alteration of Rosuvastatin therapy. Concomitant lipid-lowering therapies: Use with fibrates and niacin products may increase the risk of skeletal muscle effects.Volume of Distribution
The relative volume of distribution of ezetimibe is 107.5L.
Elimination Route
Administration of a single 10-mg dose of ezetimibe in fasted adults resulted in peak plasma concentrations (Cmax) of 3.4-5.5 ng/mL within 4-12 hours (Tmax). The Cmax of the major pharmacologically-active metabolite, ezetimibe-glucuronide, was 45-71 ng/mL and its Tmax was 1-2 hours. Food consumption has minimal effect on ezetimibe absorption, but the Cmax is increased by 38% when administered alongside a high-fat meal. The true bioavailability of ezetimibe cannot be determined, as it is insoluble in aqueous media suitable for intravenous injection.
Half Life
Both ezetimibe and ezetimibe-glucuronide display an approximate half-life of 22 hours.
Clearance
There are no pharmacokinetic data available on the clearance of ezetimibe.
Elimination Route
Approximately 78% and 11% of orally administered radiolabelled ezetimibe are recovered in the feces and urine, respectively. Unchanged parent drug is the major component in feces and accounts for approximately 69% of an administered dose, while ezetimibe-glucuronide is the major component in urine and accounts for approximately 9% of an administered dose. High recovery of unchanged parent drug in feces suggests low absorption and/or hydrolysis of ezetimibe-glucuronide secreted in the bile.
Pregnancy & Breastfeeding use
There are no adequate and well-controlled studies of Ezetimibe in pregnant women. Ezetimibe should be used during pregnancy only if the potential benefit justifies the risk to the fetus
The safety in pregnant women has not been established. It is not known whether Rosuvastatin is excreted in human milk or not.Contraindication
Hypersensitivity to any component of this medication. The combination of Ezetimibewith an HMG-CoA reductase inhibitor is contraindicated in patients with active liverdisease or unexplained persistent elevations in serum transaminases.
Rosuvastatin is contraindicated if- Known hypersensitivity to product components Liver disease, which may include unexplained persistent elevations in hepatic transaminase levels Pregnant women and women who may become pregnant Nursing mothersSpecial Warning
Pediatric Use-
10 to 17 years: No dosage adjustment is required. The clinical experience in pediatric and adolescent patients is however limited. When Ezetimibe is administered with statin, the dosage instructions for statin, in adolescents should be consulted.
Children < 10 years: Ezetimibe is not recommended for use in children below age 10 due to insufficient data on safety and efficacy.
Use in children: The safety and effectiveness in pediatric patients have not been established.Acute Overdose
No cases of overdosage with Ezetimibe have been reported. Administration of Ezetimibe,50 mg/day, to 15 subjects for up to 14 days was generally well tolerated. In the event ofan overdose, symptomatic and supportive measures should be employed.
Storage Condition
Store in a cool & dry place protected from light and moisture. Keep out of reach of children.
Keep below 30oC temperature, protected from light & moisture. Keep out of the reach of children.Innovators Monograph
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