Vastin is used as an adjunct to diet to reduce elevated total cholesterol, LDL cholesterol, apolipoprotein B (Apo-B), and triglyceride levels in patients who do not respond adequately to dietary and other non-drug measures.

• To reduce total and LDL cholesterol in patients with heterozygous and homozygous familial hypercholesterolemia.
• To lower elevated cholesterol and triglyceride levels in patients with mixed dyslipidemia (Fredrickson Types IIa and IIb).
• For the treatment of patients with elevated serum triglycerides in hypertriglyceridemia (Fredrickson Type IV).
• For the treatment of patients with dysbetalipoproteinemia (Fredrickson Type III).
• To reduce the risk of cardiac ischemic events in patients with asymptomatic or mild to moderate symptomatic coronary artery disease with elevated LDL cholesterol.
• To reduce total and LDL cholesterol levels in patients with hypercholesterolemia associated with or worsened by diabetes mellitus or renal transplantation.

Atorvastatin is a selective inhibitor of HMG-CoA reductase, the key enzyme responsible for converting HMG-CoA to mevalonate, a precursor of sterols including cholesterol. It reduces plasma cholesterol and lipoprotein levels by inhibiting cholesterol synthesis in the liver and increasing the number of hepatic LDL receptors, thereby enhancing LDL uptake and breakdown.

Absorption: Atorvastatin is rapidly absorbed after oral administration, with peak plasma levels reached within 1 to 2 hours. Absorption increases in proportion to the dose. The absolute bioavailability is about 14%, while the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%.

Distribution: The mean volume of distribution is approximately 381 liters. About 98% of atorvastatin is bound to plasma proteins. A blood/plasma ratio of around 0.25 indicates low penetration into red blood cells. Based on animal studies, atorvastatin may be excreted into human breast milk.

Metabolism: Atorvastatin is extensively metabolized to ortho- and para-hydroxylated derivatives and other beta-oxidation products. These metabolites also contribute to HMG-CoA reductase inhibition. Approximately 70% of the inhibitory activity is due to active metabolites. Metabolism occurs mainly via cytochrome P450 3A4 (CYP3A4), and plasma levels may increase when used with CYP3A4 inhibitors such as erythromycin. In animals, the ortho-hydroxy metabolite undergoes further glucuronidation.

Excretion: Atorvastatin and its metabolites are mainly excreted in bile following hepatic and extra-hepatic metabolism. The drug does not appear to undergo significant enterohepatic recirculation. The elimination half-life is about 14 hours, while the inhibitory activity lasts approximately 20–30 hours due to active metabolites. Less than 2% of an oral dose is excreted in urine.

Primary hypercholesterolaemia and combined hyperlipidaemia:

• Adults: Usually 10 mg once daily; if required, the dose may be increased at intervals of at least 4 weeks up to a maximum of 80 mg once daily.
• Children (10–18 years): Initial dose 10 mg once daily; may be increased, if necessary, at intervals of at least 4 weeks to a usual maximum of 20 mg once daily.

Familial hypercholesterolaemia:

• Adults: Starting dose is 10 mg once daily, increased at intervals of at least 4 weeks up to 40 mg once daily; if needed, further increased up to a maximum of 80 mg once daily (or 40 mg once daily in combination with anion-exchange resin in heterozygous familial hypercholesterolaemia).
• Children (10–18 years): Initial dose 10 mg once daily; may be increased at intervals of at least 4 weeks up to a maximum of 80 mg once daily.

Prevention of cardiovascular events:

• Adults: Initial dose 10 mg once daily, adjusted according to patient response.

Another guideline: Patients should begin a standard cholesterol-lowering diet before starting atorvastatin and continue this diet during treatment. The recommended starting dose is 10 or 20 mg once daily. Patients needing greater LDL-C reduction (more than 45%) may start at 40 mg once daily. The dosage range is 10–80 mg once daily. Atorvastatin can be taken at any time of the day, with or without food. Lipid levels should be assessed within 2–4 weeks after initiation, and dosage adjusted accordingly.

In pediatric patients (10–17 years), the recommended starting dose is 10 mg/day, with a maximum of 20 mg/day (higher doses have not been studied). Dosage should be individualized based on treatment goals, with adjustments made at intervals of at least 4 weeks.

Atorvastatin should not be used in patients with known hypersensitivity to any component of the medication. It is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases. It is also contraindicated in patients with a history of serious adverse reactions to HMG-CoA reductase inhibitors.

Atorvastatin is generally well tolerated. The most common side effects include constipation, flatulence, dyspepsia, and abdominal pain. Other reported adverse effects include infections, headache, back pain, rash, weakness (asthenia), joint pain (arthralgia), and muscle pain (myalgia).

Pregnancy: Atorvastatin is contraindicated during pregnancy. Its safety in pregnant women has not been established, and no adequate controlled studies are available. Rare cases of congenital abnormalities have been reported following intrauterine exposure to HMG-CoA reductase inhibitors. Animal studies have shown reproductive toxicity. Treatment with atorvastatin may reduce fetal levels of mevalonate, a precursor of cholesterol synthesis. Therefore, it should not be used in women who are pregnant, planning to become pregnant, or suspected to be pregnant. Therapy should be discontinued during pregnancy or until pregnancy is ruled out.

Lactation: It is not known whether atorvastatin or its metabolites are excreted in human milk. In animal studies, similar levels have been found in plasma and milk. Due to the potential for serious adverse effects in infants, women taking atorvastatin should not breastfeed. Atorvastatin is contraindicated during breastfeeding.

Liver effects: Liver function tests should be conducted before starting treatment and periodically during therapy. Atorvastatin should be used cautiously in patients who consume large amounts of alcohol or have a history of liver disease. Treatment should be discontinued if significantly elevated CPK levels occur or if myopathy is diagnosed or suspected.

Geriatric: Plasma concentrations of atorvastatin are higher in elderly individuals (≥65 years), with approximately 40% higher Cmax and 30% higher AUC compared to younger adults. Clinical data suggest a greater LDL-C-lowering effect in elderly patients at any given dose.

Pediatric: Pharmacokinetic data in pediatric patients are limited.

Gender: No clinically significant difference in LDL-C reduction has been observed between men and women.

Renal Insufficiency: Renal impairment does not significantly affect plasma concentrations or LDL-C reduction; therefore, dose adjustment is generally not required.

Hemodialysis: Hemodialysis is unlikely to significantly increase the clearance of atorvastatin due to its high protein binding.

Hepatic Insufficiency: In patients with chronic alcoholic liver disease, plasma concentrations of atorvastatin may be significantly increased.

There is no specific antidote available for atorvastatin overdose. Management should be symptomatic and supportive as required. Liver function tests should be carried out and serum CK levels should be monitored. Due to the high plasma protein binding of atorvastatin, hemodialysis is unlikely to significantly enhance its clearance.

Other anti-anginal and anti-ischemic drugs; statins.

Store in a dry place, protected from light and heat. Keep out of reach of children.