• Lipid-lowering therapy (Xerova EZ 10 mg+10 mg) should be part of a comprehensive risk-reduction plan for patients at high risk of atherosclerotic cardiovascular disease.
• Should be used alongside lifestyle modifications, including a diet low in saturated fat and cholesterol.
• Drug therapy is indicated when diet and other non-pharmacological measures alone are insufficient.

Atorvastatin works by lowering plasma cholesterol and lipoprotein levels through inhibition of HMG-CoA reductase, the key enzyme involved in cholesterol synthesis in the liver. This action reduces cholesterol production and increases the number of LDL receptors on hepatocyte surfaces, thereby enhancing the uptake and breakdown of LDL cholesterol. Additionally, it decreases the production of LDL and reduces the number of circulating LDL particles.

Ezetimibe lowers blood cholesterol by inhibiting its absorption in the small intestine. It specifically targets the sterol transporter Niemann-Pick C1-Like 1 (NPC1L1), which plays a central role in the intestinal uptake of cholesterol and plant sterols. By acting at the brush border of the small intestine, ezetimibe reduces the delivery of cholesterol to the liver. Clinical studies have shown that it can significantly decrease intestinal cholesterol absorption without affecting fat-soluble vitamins such as A, D, and E, or interfering with adrenal steroid hormone production. Unlike statins, ezetimibe does not inhibit cholesterol synthesis in the liver or increase bile acid excretion

The dosage range is 10/10 mg to 80/20 mg daily. The recommended starting dose is 10/10 mg or 20/10 mg daily. This can be administered as a single dose at any time of the day, with or without food. The recommended starting dose for patients who require a larger reduction in LDL-C (greater than 55%) is 40/10 mg daily. After initiation and/or upon titration of this medicine, lipid levels should be analyzed within 2 or more weeks and dosage adjusted accordingly.

Patients with Homozygous Familial Hypercholesterolemia: The dosage in patients with homozygous familial hypercholesterolemia is 40/10 mg or 80/10 mg daily. This should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

Patients with Hepatic Impairment: This is contraindicated in patients with active liver disease or unexplained persistent elevations in hepatic transaminase levels

Patients with Renal Impairment: A history of renal impairment may be a risk factor for statin-associated myopathy. These patients need closer monitoring for skeletal muscle effects. In patients with renal impairment, no dosage adjustment is necessary

• Risk of myopathy is increased with Atorvastatin when used with:
  • Fibric acid derivatives
  • Lipid-modifying doses of niacin
  • Cyclosporine
  • Strong CYP3A4 inhibitors (e.g., clarithromycin, HIV protease inhibitors, itraconazole)
• Concomitant use with cyclosporine should be avoided.
• Co-administration with gemfibrozil is not recommended due to increased risk of myopathy and rhabdomyolysis, especially with HMG-CoA reductase inhibitors.
• Use with niacin may further increase the risk of skeletal muscle adverse effects.
• Patients taking digoxin should be appropriately monitored.
• Increased exposure (AUC) of norethindrone and ethinyl estradiol may occur; this should be considered when selecting oral contraceptives.
• Caution is advised when used with colchicine.
• When used with warfarin or other coumarin anticoagulants, the International Normalized Ratio (INR) should be closely monitored to ensure safe and effective anticoagulation.

• Pregnancy Category X
• This tablet is contraindicated in women who are pregnant or may become pregnant.
• During normal pregnancy, cholesterol and triglyceride levels naturally increase.
• Lipid-lowering therapy provides no benefit during pregnancy because cholesterol is essential for fetal development.
• Atherosclerosis is a long-term process; temporary discontinuation during pregnancy is unlikely to affect long-term treatment outcomes of hypercholesterolemia.
• It is unknown whether Atorvastatin is excreted in human breast milk.
• However, small amounts of other drugs in the same class may pass into breast milk, so caution is advised during breastfeeding.

• Cases of myopathy, including rhabdomyolysis, have been reported with Atorvastatin when used with colchicine.
  • Caution should be exercised when prescribing this combination.
  • Therapy should be temporarily withheld or discontinued in patients with acute serious conditions suggestive of myopathy or those at risk of renal failure due to rhabdomyolysis.
• Liver Enzymes:
  • Liver function tests should be performed before starting therapy and repeated when clinically indicated.
  • If serious liver injury occurs with symptoms, or if hyperbilirubinemia or jaundice develops, treatment should be stopped immediately.
  • If no other cause is identified, the combination should not be restarted.
  • Active liver disease or unexplained persistent elevation of transaminases is a contraindication.
• Endocrine Function:
  • Caution is required when used with drugs that may reduce endogenous steroid hormone levels or activity, such as ketoconazole, spironolactone, and cimetidine.

• Pediatric Use:
  • Safety and effectiveness have not been established in pediatric patients.
  • Atorvastatin is not routinely recommended for use in children.
• Geriatric Use:
  • No dosage adjustment is required in elderly patients.
  • Therapy should be guided by clinical response and patient tolerance.

• No specific antidote or targeted treatment is available for overdose of Atorvastatin.
• In case of overdose, the patient should be managed symptomatically.
• Supportive care should be provided as required based on the patient’s clinical condition.

• Other lipid-regulating drugs
• Combination therapy of Atorvastatin and Ezetimibe belongs to lipid-lowering agents used in the management of dyslipidemia.

• Do not store above 30°C.
• Keep in a dry place.
• Protect from light.
• Keep out of reach of children.