Atorvastatin + Ezetimibe

Atorvastatin + Ezetimibe is a combination of two medicines used to treat high cholesterol. Atorvastatin inhibits HMG-CoA reductase in the liver, reducing cholesterol synthesis and increasing LDL receptors. Ezetimibe inhibits cholesterol absorption in the small intestine, decreasing cholesterol delivery to the liver.

This combination provides better cholesterol reduction through two complementary mechanisms. Common side effects include nausea, constipation, stomach pain, headache, and muscle pain.

• Primary hyperlipidemia (heterozygous familial and non-familial) or mixed hyperlipidemia - to reduce total-C, LDL-C, Apo B, TG, non-HDL-C and increase HDL-C
• Homozygous Familial Hypercholesterolemia (HoFH) - as an adjunct to other lipid-lowering treatments

Atorvastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis in the liver, and increases hepatic LDL receptors to enhance LDL catabolism.

Ezetimibe localizes at the brush border of the small intestine and inhibits cholesterol absorption. Its molecular target is the sterol transporter Niemann-Pick C1-Like 1 (NPC1L1), involved in intestinal cholesterol uptake. Clinical studies have shown ezetimibe inhibits intestinal cholesterol absorption by 54%.

Atorvastatin reduces hepatic cholesterol synthesis and increases LDL receptor-mediated clearance of LDL from the blood. Ezetimibe reduces intestinal cholesterol absorption, decreasing cholesterol delivery to the liver. Together, they effectively lower blood cholesterol levels through complementary mechanisms.

Adults:

• Recommended starting dose: 10/10 mg or 20/10 mg once daily
• If >55% LDL-C reduction needed: Start with 40/10 mg daily
• Dose range: 10/10 mg to 80/20 mg daily
• Dose adjustment: Lipid levels should be checked after 2 or more weeks and dosage adjusted accordingly

Homozygous Familial Hypercholesterolemia (HoFH):

• Dose: 40/10 mg or 80/10 mg daily
• Use as adjunct to other lipid-lowering treatments or if such treatments are unavailable

Renal Impairment: No dose adjustment needed, but close monitoring for muscle effects is required.

Hepatic Impairment: Contraindicated in active liver disease or unexplained persistent transaminase elevations.

Take once daily at any time, with or without food. Swallow the tablet whole - do not chew, crush, or break.

If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.

• Nausea
• Constipation
• Stomach pain
• Headache
• Muscle pain
• Increased liver enzymes
• Increased blood glucose

Serious (rare): Rhabdomyolysis, myopathy, liver injury

Serious Precautions:

• Report any muscle pain or weakness (especially with fever) to your doctor
• Report signs of liver damage (abdominal pain, loss of appetite, dark urine, yellow skin/eyes)
• Do not use during pregnancy and breastfeeding
• Contraindicated in active liver disease or unexplained persistent transaminase elevations
• Regular monitoring of blood sugar and liver function recommended
• Caution with alcohol consumption

• Active liver disease or unexplained persistent transaminase elevations
• Hypersensitivity to atorvastatin, ezetimibe, or any component
• Pregnancy and lactation

• Cyclosporine: Avoid co-administration
• Gemfibrozil: Increases risk of myopathy/rhabdomyolysis - avoid
• CYP3A4 Inhibitors (clarithromycin, HIV protease inhibitors, itraconazole): Increase risk of myopathy
• Fibrates, niacin: May enhance muscle effects
• Digoxin: May increase digoxin levels - monitor appropriately
• Warfarin: Monitor INR when added
• Colchicine: Use with caution
• Cholestyramine: Decreases ezetimibe AUC by ~55%
• Antacids: Decrease atorvastatin levels

[UNSAFE] Alcohol with Atorvastatin + Ezetimibe may increase the risk of liver problems.

[UNSAFE] Do not use during pregnancy (Category X). Cholesterol is essential for normal fetal development.

[CONSULT YOUR DOCTOR] It is unknown whether atorvastatin + ezetimibe is excreted in human milk. Caution is advised during breastfeeding.

Safety and efficacy have not been established in pediatric patients.

No dose adjustment is necessary for elderly patients.

Renal Impairment: No dose adjustment needed, but close monitoring for muscle effects is required.

Hepatic Impairment: Contraindicated in active liver disease or unexplained persistent transaminase elevations. Not recommended in moderate to severe liver disease.

No specific treatment for overdose can be recommended. Symptomatic and supportive treatment should be provided.

Store below 30°C, in a dry place, protected from light. Keep out of reach of children.

Atorvastatin (C₃₃H₃₅FN₂O₅) + Ezetimibe (C₂₄H₂₁F₂NO₃)