Indications

ATV is indicated as an adjunct to diet to reduce elevated levels of total cholesterol, LDL cholesterol, apolipoprotein B (Apo-B), and triglycerides when a response to diet and other non-pharmacological measures is inadequate. It is used to treat:

• Familial hypercholesterolemia (heterozygous and homozygous).
• Mixed dyslipidemia (Fredrickson Type Ia and Ib).
• Hypertriglyceridaemia (Fredrickson Type IV).
• Dysbetalipoproteinaemia (Fredrickson Type III).
• High LDL-cholesterol levels in patients with coronary artery disease to reduce cardiac ischemic events.
• Hypercholesterolemia associated with or made worse by diabetes mellitus or renal transplantation.

Pharmacology

Atorvastatin, the active ingredient, is a selective inhibitor of HMG-CoA reductase, an enzyme crucial for the production of cholesterol in the liver. By blocking this enzyme, atorvastatin lowers plasma cholesterol and lipoprotein levels. It also increases the number of LDL receptors on the surface of liver cells, which enhances the breakdown of LDL.

Atorvastatin is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. Its bioavailability is low (about 14%), and 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 to 30 hours, and it is primarily eliminated in bile.

Dosage & Administration

• Primary hypercholesterolaemia and combined hyperlipidaemia:
  • Adults: Usually 10 mg once daily, which may 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: Initially 10 mg daily, increased 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 Guidelines: The dosage range is 10 to 80 mg once daily. It can be taken as a single dose at any time of day, with or without food. Lipid levels should be checked within 2 to 4 weeks after starting or adjusting the dose.

Interaction

• Myopathy Risk: Concurrent use with cyclosporine, fibric acid derivatives, niacin, erythromycin, or azole antifungals increases the risk of myopathy.
• Antacids & Colestipol: These can decrease atorvastatin plasma concentrations, but the LDL-C reduction effect is not significantly altered.
• Digoxin: Coadministration can increase digoxin plasma concentrations, requiring monitoring.
• Erythromycin: Can increase atorvastatin plasma concentrations.
• Oral Contraceptives: Can increase the levels of hormones in oral contraceptives.
• Warfarin: ATV does not have a clinically significant effect on prothrombin time in patients on chronic warfarin.

Contraindications

ATV is contraindicated in patients with 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 other 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 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, a precursor to cholesterol biosynthesis. Women who are pregnant, trying to become pregnant, or suspect they are pregnant should not use this medication. It is not known whether atorvastatin is excreted in human milk, but 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 significant alcohol consumption.
• Myopathy: Therapy should be stopped if there is a marked elevation in CPK levels or if myopathy is diagnosed or suspected.

Use in Special Populations

• Geriatric: Plasma concentrations are higher in elderly patients, but this may lead to a greater LDL-lowering effect.
• 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 be treated symptomatically and with supportive care. Liver function tests and serum CK levels should be monitored. Hemodialysis is not effective at clearing atorvastatin due to its extensive 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.