ASPAVOR Film-coated tablet Ref.[50587] Active ingredients: Atorvastatin

Liver Effects

Persistent elevations (>3 times the upper limit of normal (ULN) occurring on 2 or more occasions) in serum transaminases occurred in 0,7% of patients who received atorvastatin in clinical trials. The incidence of these abnormalities was 0,2%, 0,2%, 0,6% and 2,3% for 10, 20, 40 and 80 mg respectively.

It is recommended that liver function tests be performed before the initiation of treatment, following each dosage increase, and periodically thereafter. Liver enzyme changes mostly commence in the first 4 months of treatment with atorvastatin. Patients who develop increased transaminase levels should be monitored until the abnormalities resolve. Should an increase in ALT or AST of >3 times ULN persist, withdrawal of atorvastatin is recommended.

ASPAVOR should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Active liver disease or unexplained persistent transaminase elevations are contra-indications to the use of ASPAVOR.

Skeletal Muscle

Rhabdomyolysis with or without renal impairment has been reported with the use of HMG-CoA reductase inhibitors.

Myalgia has been reported in patients treated with ASPAVOR (see SIDE-EFFECTS). Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values greater than 10 times the upper limit of normal, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/ormarked elevation of CPK. Patients should be advised to report promptly any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. ASPAVOR therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected.

As with other HMG-CoA reductase inhibitors, the risk of myopathy during treatment with ASPAVORis increased with concurrent administration of immunosuppressive drugs, including cyclosporine, fibric acid derivatives, nicotinic acid, azole antifungals or erythromycin (see INTERACTIONS).

ASPAVOR therapy should be withdrawn in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis, (e.g., severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).

As with other HMG-CoA reductase inhibitors the risk of myopathy during treatment with ASPAVOR is increased with concurrent administration of immunosuppressive drugs, fibric acid derivatives, macrolide antibiotics, e.g. erythromycin, azole antifungals, e.g. clotrimazole, or niacin (nicotinic acid) (see WARNINGS: Skeletal Muscle).

Antacid

Co-administration of an oral antacid suspension containing magnesium and aluminium hydroxides with ASPAVOR decreased plasma concentrations of atorvastatin approximately 35%; however, LDL-C reduction was not altered.

Antipyrine

Because ASPAVOR does not affect the pharmacokinetics of antipyrine, interactions with other drugs metabolized via the same cytochrome isozymes are not expected.

Colestipol

Plasma concentrations of atorvastatin decreased approximately 25% when colestipol and ASPAVOR were co-administered. However, LDL-C reduction was greater when ASPAVOR and colestipol were co-administered than when either drug was given alone.

Cholestyramine

No data is available.

Cimetidine

Atorvastatin plasma concentrations and LDL-C reduction were not altered by co-administration of cimetidine.

Digoxin

Co-administration of multiple doses of ASPAVOR and digoxin increased steady-state plasma digoxin concentrations by approximately 20%. Patients taking digoxin should be monitored appropriately.

Erythromycin

In healthy individuals, plasma concentrations of ASPAVOR increased approximately 40% with co-administration of ASPAVOR and erythromycin, a known inhibitor of cytochrome P4503A4 (see WARNINGS, Skeletal Muscle).

Oral contraceptives

Co-administration of ASPAVOR and an oral contraceptive increased AUC values of norethindrone and ethinyl estradiol approximately 30% and 20%, respectively. These increases should be considered when selecting an oral contraceptive for a woman taking atorvastatin.

Warfarin

ASPAVOR had no clinically significant effect on prothrombin timewhen administered to patients receiving combined ASPAVOR and warfarin therapy for two weeks. Nevertheless, patients receiving ASPAVOR should be closely monitored when ASPAVOR is combined with warfarin therapy.

Other Concomitant Therapy

In clinical studies, ASPAVOR was used concomitantly with antihypertensive agents and oestrogen replacement therapy without evidence of clinically significant adverse interactions. Interaction studies with specific agents have not been conducted.

Atorvastatin is generally 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.

Adverse events have been categorised as follows: Very common: ≥1/10 (≥10%), Common: ≥1/100 and 1/10 (≥1% and <10%), Uncommon: ≥1/1000 and <1/100 (≥0.1% and <1%), Rare: ≥1/10000 and <1/1000 (≥0.01% and <0.1%), Very Rare: <1/10000 (<0.01%)