Atorvastatin calcium INN

To be submitted at the time of inclusion.

Film Coated Tablet.
Each tablet contains Atorvastatin calcium equivalent to Atorvastatin INN 10 mg.

Atorvastatin is indicated as an adjunct to diet to reduce elevated total-C, LDL-C, apo-B, and TG levels in patients with primary hypercholesterolemia (heterozygous familial and non-familial) and mixed lipidemia. Atorvastatin is also indicated to reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid lowering treatments (e.g. LDL aphorises) or if such treatments are unavailable. Prior to initiating therapy with atorvastatin, secondary causes for hypercholesterolmia (e.g. poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, other drug therapy, and alcoholism) should be identified and treated.

i) Atrovastatin can be administrated within the dosage range of 10-80 mg/day as a single daily dose. Atorvastatin can be taken at any time of the day, with of without food. Therapy should be individualized according to the target lipid levels, the recommended goal of therapy, and the patient's response. After initial and/ or upon titration of atorvastain, lipid levels should be re-analyzed within 4 weeks and dosage adjusted according to the patient's response.
ii) Renal disease has no influence on the plasma concentrations or on the LDL-C reduction of atorvastatin: thus, no adjustment of the dose is required. Plasma concentrations of atorvastatin are markedly increased in patients with chronic alcoholic liver disease (Childs-Pugh B). The benefits of therapy should be weighed against the risks when atorvastatin is to be given to patients with hepatic insufficiency.

The absolute contra-indications to the administration of atorvastatin include active liver disease or unexplained persistent elevations of serum transaminases and hypersensitivity to any component of this medication.

Atorvastatin is well-tolerated. Adverse reactions have usually been mild and transient. Less than 2% of patients were discontinued from clinical trials due to side effects attributed to atorvastatin. The most frequent (>1%) adverse effects associated with atorvastain therapy in patients participating in controlled clinical studies were constipation, flatulence, dyspepsia, abdominal pain, headache, nasuea, myalgia, asthenia, diarrhea and insomnia. Atorvastatin can cause elevation in ALT/AST, alkaline phosphatase, GGT, bilirubin and creatine phosphokinase.

Based on experience with other HMG-CoA reductase inhibitors, caution should be exercised when atrovastatin is administered with inhibitors of cytochrome P450 3A4 (e.g. cyclosporin, macrolide antibiotics including erythromycin and azole antifungals or niacin). Co-administration of an oral antacid suspension, containing magnesium and aluminium hydroxide, with atorvastatin decreased atorvastatin plasma concentrations approximately 35%, however, LDL-C reduction was not altered. Plasma concentrations of atorvastatin were lower (approximately 25%) when cholestyramine was co-administered than when either drug was given alone. Co-adminstration of multiple doses of atorvastatin and digoxin increased steady-state plasma digoxin concentrations by approximately 20%. Patients taking digoxin should be monitored appropriately.

The safety & effectiveness of Atorvastatin have not been established in paediatric patients & adolescents less than 18 years of age.

Cholesterol and other products of cholesterol biosynthesis are essential for fetal development (including synthesis of steroids and cell membranes). Since HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, they may cause fetal harm when administered to pregnant women. Therefore, HMG-CoA reductase inhibitors are contraindicated during pregnancy and in nursing mothers. Atorvastatin should be administered to women of child-bearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the patient becomes pregnant while taking this drug, therapy should be discontinued and the patient appraised of the potential hazard to the fetus.

There is no specific treatment for atorvastatin over dosage. should an over dosage occur, the patient should be treated symptomatically, and supportive measures instituted as required. Due to extensive drug binding to plasma proteins, haemodialysis is not expected to significantly enhance atorvastatin clearance.

Box containing 3 X 10 Tablets in blister pack.