Atorvastatin +
Ezetimibe Tablets

Mechanism

Atorvastatin inhibits HMG-CoA reductase, reducing cholesterol synthesis in the liver. Ezetimibe blocks cholesterol absorption from the small intestine. Together, they significantly reduce total cholesterol and LDL levels.

Pharmacodynamics

The combination provides additive lipid-lowering effects by targeting both endogenous cholesterol production and exogenous absorption, leading to improved lipid profile and cardiovascular protection.

Pharamcokinetics

• Atorvastatin: After oral administration, Atorvastatin is rapidly absorbed, with peak serum concentrations reaching within 1 to 2 hours. Extent of absorption increases in proportion to Atorvastatin dose. The absolute bioavailability of Atorvastatin is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. Mean volume of distribution is approximately 381 liters. Atorvastatin is ≥ 98% bound to plasma proteins. Atorvastatin is extensively metabolized to ortho-and para hydroxylated derivatives and various beta-oxidation products. Approximately 70% of circulatory inhibitory activity for HMG-CoA reductase is attributed to active metabolites. Atorvastatin and its metabolites are eliminated primarily in bile following hepatic and/or extrahepatic metabolism; however the drug does not appear to undergo enterohepatic recirculation. Mean plasma elimination half life of Atorvastatin in humans is approximately 14 hrs, but the half life of inhibitory activity for HMG-CoA reductase is 20-30 hours due to contribution of active metabolites.
• Ezetimibe: Ezetimibe is rapidly absorbed and conjugated after oral administration. Tmax of Ezetimibe and Ezetimibe-glucuronide are 4-12 hrs and 1-2 hrs respectively. Concomitant food administration (high fat or non-fat meals) has no effect on the extent of absorption of Ezetimibe. Ezetimibe can be administered with or without food. Ezetimibe and Ezetimibe-glucuronide are highly bound (>90%) to human plasma proteins. In humans, Ezetimibe gets rapidly metabolized to Ezetimibe-glucuronide. Ezetimibe and Ezetimibe glucuronide are the major drug-derived compounds detected in plasma, constituting approximately 10-20% and 80-90% of the total drug in plasma, respectively. Both Ezetimibe and Ezetimibe-glucuronide are slowly eliminated from plasma with a half-life of approximately 22 hours for both Ezetimibe and Ezetimibe-glucuronide.
  From the pharmacokinetic profile, it is clear that both the drugs are rapidly absorbed after oral administration. The Tmax for Atorvastatin and Ezetimibe glucuronide (pharmacologically active metabolite of Ezetimibe) are also same (i.e. 1-2 hours) which further supports their use in fixed dose combination as a single dose. Further Atorvastatin and Ezetimibe can be administered as a single dose at any time of the day with or without food.

Side Effects

• Headache
• Muscle pain (myalgia)
• Abdominal discomfort
• Diarrhea
• Elevated liver enzymes

Contraindication

• Active liver disease
• Pregnancy and lactation
• Hypersensitivity to components

Interaction

• Cyclosporine
• Fibrates (increased risk of myopathy)
• Anticoagulants
• Grapefruit juice (increases statin levels)

Warning and Precautions

This has been prescribed for the patient's specific condition. It may be dangerous to any other person.

• Monitor liver function regularly
• Use cautiously in patients with liver impairment
• Risk of muscle toxicity (myopathy/rhabdomyolysis)
• Avoid during pregnancy