T H E R A P E U T I C I N D E X

Atova ®
Tablet

Description
Atova is a preparation of Atorvastatin Calcium, which is a synthetic lipid
lowering agent. It is an inhibitor of 3-hydroxy-3-methyl-glutaryl-
coenzyme A (HMG-CoA). This enzyme catalyses the conversion of
HMG-CoA to mevatonate, an early and rate limiting step in the synthesis
of cholesterol.

Indications
Atova is indicated as an adjunct to diet to reduce elevated total cholesterol
(C), low density lipoprotein-cholesterol (LDL-C), apolipoprotein B and
triglyceride (TG) levels in patients with primary hypercholesterolaemia
(heterozygous familial and non familial) and mixed dyslipidaemia
(Fredrickson Types lla and llb).

Atova is indicated as adjunctive therapy to diet for the treatment of

patients with elevated serum triglyceride levels (Fredrickson Type IV).

Atova is indicated for the treatment of patients with primary

dysbetalipoproteinaemia (Fredrickson Type III) who do not respond
adequately to diet.

Atova is also indicated to reduce total C and LDL-C in patients with

homozygous familial hypercholesterolaemia as an adjunct to other lipid
lowering treatments (e.g., LDL apheresis) or if such treatments are
unavailable.

Therapy with lipid altering agent should be a component of multiple risk

factor intervention in individuals at increased risk for atherosclerotic vascular
disease due to hypercholesterolaemia. Lipid altering agents should be used in
addition to a diet restricted in saturated fat and cholesterol only when the
response to diet and other nonpharmacological measures have been
inadequate (see Table 1). At the time of hospitalisation for an acute coronary
event, consideration can be given to initiating drug therapy at discharge if the
LDL-C level is >130 mg/dl [National Cholesterol Education Program
(NCEP) Adult Treatment Panel II (ATP II)].

42
T H E R A P E U T I C I N D E X

Prior to initiating therapy with Atova, secondary causes for

hypercholesterolaemia (e.g., poorly controlled diabetes mellitus,
hypothyroidism, nephrotic syndrome, dysproteinaemias, obstructive liver
disease, other drug therapy, and alcoholism) should be excluded, and a
lipid profile performed to measure total-C, LDL-C, HDL-C, and TG. For
patients with TG< 400 mg/dl (< 4.5 mmol/L), LDL-C can be estimated
using the following equation : LDL-C=total-C (0.20 x [TG] + HDL-C).
For TG levels > 400 mg/dl (> 4.5 mmol/L), this equation is less accurate
and LDL-C concentrations should be determined by ultracentrifugation.
Atorvastatin has not been studied in conditions where the major
lipoprotein abnormality is elevation of chylomicrons (Fredrickson Types
I and V).

TABLE 1 - NCEP GUIDELINES FOR LIPID MANAGEMENT

Definite Two or More LDL-Cholesterol mg/dl (mmol/L)
Atherosclerotic other
Diseasea Risk Factorsb
Initiation Level Minimum Goal
No No > 190 (> 4.9) < 160 (< 4.1)

No Yes > 160 (> 4.1) < 130 (< 3.4)

Yes Yes or No > 130 c (> 3.4) < 100 (< 2.6)

a. Coronary heart disease or peripheral vascular disease (including symptomatic carotid

artery disease).

b. Other risk factors for coronary heart disease (CHD) include : age (males > 45 years;
females > 55 years or premature menopause without estrogen replacement therapy);
family history of premature CHD; current cigarette smoking; hypertension;
confirmed HDL-C < 35 mg/dl (< 0.91 mmol/L); and diabetes mellitus. Subtract 1
risk factor if HDL-C is > 60 mg/dl (> 1.6 mmol/L).

c. In CHD patients with LDL-C levels 100 to 129 mg/dl, the physician should exercise
clinical judgement in deciding whether to initiate drug treatment.

Dosage and Administration

Adults : The patient should be placed on a standard cholesterol lowering
diet before receiving Atova and should continue on this diet during
treatment with Atova.

43
T H E R A P E U T I C I N D E X

Hypercholesterolaemia (Heterozygous Familial and Nonfamilial) and Mixed

Dyslipidaemia (Fredrickson Types IIa and IIb) : The recommended starting
dose of Atova is 10 mg daily. The dosage range is 10 to 80 mg once daily.
Atova can be administered as a single dose at any time of the day with or
without food. Therapy should be individualised according to goal of
therapy and response. After initiation and/or upon titration of Atova,
lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted
accordingly.

Since the goal of treatment is to lower LDL-C, the LDL-C levels should
be used to initiate and assess treatment response. Only if LDL-C levels
are not available, total-C should be used to monitor therapy.

Homozygous familial hypercholesterolaemia : The dosage of Atova in patients

with homozygous Familial Hypercholesterolaemia is 10 to 80 mg daily.
Atova should be used as an adjunct to other lipid lowering treatments
(e.g., LDL apheresis) in these patients or if such treatments are
unavoidable.

Patients with renal insufficiency : Renal disease has no influence on the plasma
concentrations or lipid effects of Atorvastatin; thus no adjustment of
dose is required. Haemodialysis is not expected to significantly enhance
the clearance of Atorvastatin since the drug is extensively bound to
plasma proteins.

Patients with hepatic dysfunction : In patients with moderate to severe hepatic

dysfunction, the therapeutic response to Atorvastatin is unaffected but
exposure to the drug is greatly increased. Cmax increases by approximately
16 fold and area under curve AUC (0-24) by approximately 11 fold.
Therefore, caution should be exercised in patients who consume
substantial quantities of alcohol and/or have a history of liver disease.

Contraindications
Hypersensitivity to any component of this medication. Active liver
disease or unexplained persistent elevations of serum transaminases
exceeding three times the upper limit of normal.

Precautions
Rhabdomyolysis with acute renal failure secondary to myoglobinuria has
been reported with other drugs in this class. Atorvastatin may cause an

44
T H E R A P E U T I C I N D E X

elevation in serum creatinephosphokinase (CPK) levels. This should be

considered in the differential diagnosis of chest pain in patients on
therapy with Atorvastatin. 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.

The risk of myopathy during treatment with other drugs in this class is
increased with concurrent administration of Cyclosporin, fibric acid
derivatives, Erythromycin, Niacin, or azole anti-fungals. Patients should
be advised to report promptly any unexplained muscle pain, tenderness or
weakness, particularly if accompanied by malaise or fever.

Side Effects
Atorvastatin is generally well tolerated. Adverse effects reported
commonly include constipation, flatulence, dyspepsia, abdominal pain,
headache, nausea, myalgia, diarrhoea, asthenia and insomnia.

Dose related and reversible elevated serum alanine transaminase (ALT)

levels have been reported in approximately 1.3% of patients receiving
Atorvastatin.

Elevated serum CPK levels have been reported in some patients on

Atorvastatin but only in rare cases patients may have muscle pain,
tenderness or weakness. Other side effects reported in clinical trials (not all
effects have necessarily been associated with Atorvastatin therapy) include
muscle cramps, myopathy, paresthesia, peripheral neuropathy, pancreatitis,
hepatitis, cholestatic jaundice, anorexia, vomiting, pruritus, rash,
impotence, hyperglycaemia and hypoglycaemia. Chest pain, dizziness,
angina and allergic reactions have been reported in isolated cases.

Use in Special Populations

Pregnancy : Safety in pregnancy has not been established. Rare reports of
congenital anomalies have been reported following intrauterine exposure
to HMG-CoA reductase inhibitors. HMG-CoA reductase inhibitors are
not recommended for use during pregnancy. An interval of 1 month
should be allowed from stopping Atorvastatin treatment to conception in
the event of planning a pregnancy.

45
T H E R A P E U T I C I N D E X

Lactation : Use of HMG-CoA reductase inhibitors during breast feeding is

not recommended, because of the potential for serious adverse effects in
nursing infants.

Children : Safety and efficacy of Atorvastatin have not been established in

children.

Geriatrics : Efficacy and safety in older patients using recommended doses

is similar to that seen in the general population.

Commercial Packs
Atova® 10 Tablet : Box containing 30 tablets in 3 x 10’s blister strip, each
tablet contains Atorvastatin Calcium INN equivalent to Atorvastatin 10 mg.

Atova® 20 Tablet : Box containing 10 tablets in 1 x 10’s blister strip, each

tablet contains Atorvastatin Calcium INN equivalent to Atorvastatin 20 mg.

46