ANZITOR

ATORVASTATIN CALCIUM

Atorvastatin is indicated as an adjunct to diet for reduction of elevated total cholesterol, LDL-cholesterol, apolipoprotein B, and triglycerides in patients with- Primary hypercholesterolemia- heterozygous familial and non-familial hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb) Elevated serum TG levels (Fredrickson type IV) Primary dysbetalipoproteinemia (Fredrickson type III) who do not respond adequately to diet. Homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (LDL apheresis) or if such treatments are unavailable.

Other Anti-anginal & Anti-ischaemic drugs, Statins

Atorvastatin is a synthetic lipid lowering agent. It is a selective, competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis.

Patients should be placed on a standard cholesterol-lowering diet before receiving Atorvastatinand should continue on this diet during treatment with Atorvastatin. The usual starting dose for all the indications is 10mg once daily. The doses range is 10 to 80 mg once daily. Doses should be individualised according tobaseline LDL-C levels, the goal of therapy, and patient response. Adjustment of dosage should be made atintervals of 4 weeks or more. Doses may be given at anytime of day with or without food. Children: Treatment experience in a paediatric population with dose of Atorvastatin up to 80 mg/day is limited. Geriatric (>70 years): The safety and efficacy of Atorvastatin in this population is as similar as < 70 years of age patients with the dose upto 80 mg/day. In patients with Renal Insufficiency: No dosage adjustment is required.

The risk of myopathy during treatment with other drugs in this class is increased with concurrent administration of cyclosporin, fibric acid derivatives, erythromycin, azole antifungals, or niacin (nicotinic acid). These risks may also occur when combining these drugs with Atorvastatin. No clinically significant interactions were seen when Atorvastatin was administered with antihypertensives and or hypoglycemic agents. Caution should also be exercised when Atorvastatin is administered with inhibitors of P450 3A4 (macrolide antibiotics and azole antifungals). The effect of inducers of cytochrome P450 3A4 (rifampicin or phenytoin) on Atorvastatin is unknown. Patients should be closely monitored if Atorvastatin is added to digoxin, erythromycin, oral contraceptives, colestipol, antacid and warfarin. No interaction was found with cimetidine.

Atorvastatin is contraindicated in patients with hypersensitivity to any component of this medication, active liver disease or unexplained persistent elevations of serum transaminases, during pregnancy, while breast-feeding, and in women of child-bearing potential not using appropriate contraceptive measures.

Atorvastatin is generally well tolerated. Adverse reactions have usually been mild and transient. Reversible myositis is rare but significant side effect of the statins. The statins also cause headache, altered liver-function tests and gastro-intestinal effects including abdominal pain, flatulence, diarrhoea, nausea and vomiting. Thrombocytopenia, rash and hypersensitivity reactions have been reported rarely. Other side effects are reported with Atorvastatin therapy includes insomnia, angioedema, anorexia, asthenia, paraesthesia, peripheral neuropathy, alopecia, pruritus, rash, impotence, chest pain, hypoglycemia and hyperglycemia.

Atorvastatin is contraindicated in pregnancy and while breast-feeding. Women of child bearing potential should use appropriate contraceptive measures. If the woman become pregnant while taking Atorvastatin, it should be discontinued.

Specific treatment is not available for Atorvastatin overdosage. If an overdose occur, the patient should be treated symptomatically and supportive measures instituted, as required. Liver function tests and serum CPK levels should be monitored. Due to extensive drug binding to plasma proteins, haemodialysis is not expected to significantly enhance Atorvastatin clearance.

Liver effects: Liver function tests should be performed before the initiation of treatment and periodically thereafter. Should an increase in ALT or AST of greater than 3 times the upper limit of normal persist, reduction of dose or withdrawal of Atorvastatin is recommended. Atorvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Skeletal muscle effects: Uncomplicated myalgia has been reported in Atorvastatin- treated patients. Atorvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Should significant increases in CPK persist, reduction of dose or withdrawal of Atorvastatin is recommended. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with Atorvastatin and with other drugs in this class.

Store in a cool dry place protected from light. Keep out of reach of children.