Atorvastatin Calcium

FORMULATION
Each film-coated tablet contains:
Atorvastatin calcium USP
equivalent to Atorvastatin           …………………….    20 mg / 40 mg

PHARMACOLOGICAL ACTION
Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methyIgIutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Cholesterol and triglycerides circulate in the bloodstream as part of lipoprotein complexes. With ultracentrifugation, these complexes separate into HDL (high-density lipoprotein), IDL (intermediate-density lipoprotein), LDL (low-density lipoprotein and VLDL (very-low-density lipoprotein) fractions. Triglycerides (TG) and cholesterol in the liver are incorporated into VLDL and released into the plasma for delivery to peripheral tissues. LDL is formed from VLDL and is catabolized primarily through the high- affinity LDL receptor. Clinical and pathologic studies show that elevated plasma levels of total cholesterol(total-C), LDL-cholesterol (LDL-C) and apolipoprotein B (apo B) promote human atherosclerosis and are risk factors for developing cardiovascular disease, while increased levels Of HDL-C are associated with a decreased cardiovascular risk.

PHARMACOKINETICS
Atorvastatin is rapidly absorbed from gastrointestinal tract. It has low absolute bioavailability of about 12% to presystemic clearance in the gastrointestinal mucosa and/or first-pass metabolism in the liver, its primary site of action. Atorvastatin is metabolized by the cytochrome P4100 isoenzyme CYP3A4 to a number of compounds which are also active inhibitors of HMG-CoA reductase. The mean plasma elimination half-life Of atorvastatin is about 14 hours although the half-life Of inhibitory activity for HMG- COA reductase is approximately 20 to 30 hours due to the contribution of the active metabolites. It is 98% bound to plasma proteins. Atorvastatin is excreted as metabolites, primarily in the bile.

INDICATIONS
For the reduction of LDL cholesterol, apolipoprotein B, and triglycerides and to increase HDL-cholesterol in the treatment of hyperlipidemia including hypercholesterolemia and combined (mixed) hyperlipidemia (type lla or 11b hyperlipoproteinemia), hypertriglyceridemia (type IV), and dysbetalipoproteinaemia (type Ill). It can be effective as adjunctive therapy in patients with homozygous familial hypercholesterolemia who have some LDL-receptor function.

DOSAGE & ADMINISTRATION
The usual initial dose is 10 to 20 mg once daily. An initial dose of 40 mg daily may be used in patients who require a large reduction in LDL-cholesterol. The dose may be adjusted at intervals of 4 weeks up to a maximum of 80 mg daily. Or as prescribed by the physician.

CONTRAINDICATIONS
Atorvastatin is contraindicated in patients with known hypersensitivity to any of its ingredients.

PRECAUTIONS
Atorvastatin should not be given to patients with active liver disease or unexplained persistently raised serum aminotransferase concentrations and should be discontinued if marked or persistent increases in serum-aminotransferase concentrations occur. Atorvastatin may cause myopathy and rhabdomyolysis especially at higher doses, and they should be used with caution in patients at risk of rhabdomyolysis and particularly in patients taking drugs that increase plasma concentration of Atorvastatin and it should be discontinued if creatine phosphokinase increases significantly or if myopathy is diagnosed.

Pregnancy
Atorvastatin is generally contraindicated in pregnancy since there is a possibility that it might affect fetal sterol synthesis whereas the risk to the mother from stopping treatment temporarily is usually very low.

ADVERSE EFFECTS
The most common adverse effects are gastrointestinal disturbances. Other adverse effects reported include headache, skin rashes, dizziness, blurred vision, insomnia, and dysgeusia. Reversible increases in serum-aminotransferase concentrations may occur and liver function should be monitored. Hepatitis and pancreatitis have been reported. Hypersensitivity reactions including anaphylaxis and angioedema have also occurred. Myopathy, characterized by myalgia and muscle weakness and associated with increased creatine phosphokinase concentrations, has been reported especially in patients also taking cyclosporine, fibric acid derivatives, or nicotinic acid. Rarely, rhabdomyolysis with accurate renal failure may develop.

DRUG INTERACTION
-Increased risk of myopathy with cyclosporine, fibric acid derivatives, lipid-modifying doses of niacin or CYP450 3A4 inhibitors (e.g. erythromycin, azole antifungals).
-Increased bioavailability with OATPI Bl inhibitors(e.g. cyclosporine).
-Increased plasma concentration with CYP 450 3A4 inhibitors, diltiazem HCI, grapefruit juice, itraconazole, cyclosporine, erythromycin, clarithromycin.
-Reduced plasma concentration with CYP450 3A4 inducers (e.g. efavirenz, rifampin), antacids & colestipol.
-Increased AUC with oral contraceptives (e.g. norethindrone, ethinyl estradiol).

CAUTION
Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.

“For suspected adverse drug reaction report to the FDA: www.fda.gov.ph.”

STORAGE CONDITION
Store at temperatures not exceeding 300C.

Keep all medicines out of children’s reach.

Price/SRP per:

• SRP 16.50 per tablet