Indications

ATV is a medication used in conjunction with diet to lower high levels of total cholesterol, LDL cholesterol, apolipoprotein B (Apo-B), and triglycerides when diet and other non-drug measures are not enough. It is indicated for:

• Familial hypercholesterolemia (heterozygous and homozygous).
• Mixed dyslipidemia (Fredrickson Type Ia and Ib).
• Hypertriglyceridaemia (Fredrickson Type IV).
• Dysbetalipoproteinaemia (Fredrickson Type III).
• Reducing cardiac ischemic events in patients with asymptomatic or mild to moderate coronary artery disease and high LDL-cholesterol.
• Hypercholesterolemia associated with or worsened by diabetes mellitus or renal transplantation.

Pharmacology

Atorvastatin, the active ingredient, is a selective inhibitor of HMG-CoA reductase, an enzyme that is a key component of cholesterol synthesis in the liver. By inhibiting this enzyme, atorvastatin reduces plasma cholesterol and lipoprotein levels. It also increases the number of LDL receptors on liver cell surfaces, which enhances the uptake and breakdown of LDL.

Atorvastatin is rapidly absorbed, with peak plasma concentrations occurring within 1-2 hours. Its absolute bioavailability is approximately 14%. It is extensively metabolized in the liver by the cytochrome P450 3A4 enzyme into active metabolites. The half-life of its inhibitory activity is 20-30 hours, and it is primarily eliminated in bile.

Dosage & Administration

• Primary hypercholesterolaemia and combined hyperlipidaemia:
  • Adults: The usual starting dose is 10 mg once daily, which can be increased at intervals of at least 4 weeks to a maximum of 80 mg once daily.
  • Children (10-18 years): Initially 10 mg once daily, with a maximum of 20 mg once daily.
• Familial hypercholesterolaemia:
  • Adults: Start with 10 mg daily and increase to 40 mg once daily at intervals of at least 4 weeks. Can be further increased to a maximum of 80 mg once daily.
• Prevention of cardiovascular events:
  • Adults: Initially 10 mg once daily, adjusted based on the patient's response.
• General: The dosage range is 10 to 80 mg once daily. It can be taken at any time of day, with or without food. Lipid levels should be checked within 2-4 weeks after starting or adjusting the dose.

Interaction

• Myopathy Risk: The risk of myopathy is increased when ATV is used with cyclosporine, fibric acid derivatives, niacin, erythromycin, or azole antifungals.
• Antacids & Colestipol: These can decrease atorvastatin concentrations, but the LDL-C lowering effect is not altered.
• Digoxin: Coadministration can increase digoxin levels, so patients should be monitored.
• Erythromycin & Oral Contraceptives: Concomitant use can increase the plasma concentrations of atorvastatin and the hormones in oral contraceptives.
• Warfarin: ATV has no clinically significant effect on prothrombin time in patients on chronic warfarin treatment.

Contraindications

ATV is contraindicated in patients with a hypersensitivity to any of its components, active liver disease, or unexplained persistent elevations of serum transaminases. It is also contraindicated in patients with a history of a serious adverse reaction to HMG-CoA reductase inhibitors.

Side Effects

ATV is generally well-tolerated. The most frequent side effects are constipation, flatulence, indigestion, and abdominal pain. Other side effects can include infection, headache, back pain, rash, weakness, and joint or muscle pain.

Pregnancy & Lactation

Atorvastatin is contraindicated during pregnancy and breastfeeding. It can harm the fetus by reducing mevalonate levels, which are necessary for cholesterol biosynthesis. Women who are pregnant, trying to become pregnant, or suspect they are pregnant should not use this medication. Due to the potential for serious adverse reactions, women taking ATV should not breastfeed.

Precautions & Warnings

• Liver Effects: Liver function tests should be performed before and periodically during treatment. ATV should be used with caution in patients with a history of liver disease or who consume significant quantities of alcohol.
• Myopathy: Therapy should be discontinued if markedly elevated CPK levels occur or if myopathy is diagnosed or suspected.

Use in Special Populations

• Geriatric: Plasma concentrations are higher in elderly patients, but clinical data suggest a greater LDL-lowering effect in this group.
• Renal Insufficiency: No dose adjustment is needed for patients with kidney dysfunction.
• Hepatic Insufficiency: Plasma concentrations are significantly increased in patients with chronic alcoholic liver disease.

Overdose Effects

There is no specific treatment for an atorvastatin overdose. The patient should receive symptomatic and supportive care. Liver function tests and serum CK levels should be monitored. Hemodialysis is not expected to be effective due to the drug's high protein binding.

Therapeutic Class

ATV is classified as a statin, and also as an anti-anginal and anti-ischaemic drug.

Storage Conditions

Keep in a dry place away from light and heat. Keep out of the reach of children.