COMPOSITION :

Each f/c tablet contains: Atorvastatin calcium equivalent to Atorvastatin 10mg, 20mg, 40mg.

DESCRIPTION :

Atrovist (Atorvastatin) is a synthetic lipid-lowering agent. It is a selective competitive inhibitor of

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the

conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol

biosynthesis. Atorvastatin is rapidly absorbed after oral administration, the maximum plasma

concentrations occur within 1 - 2 hours. Extent of absorption increases in proportion to

Atorvastatin dose. Atorvastatin is given with or without food. More than 98% of Atorvastatin is

bound to plasma proteins. It is likely to be secreted in human milk. Atorvastatin and its

metabolites are eliminated primarily in bile following hepatic and / or extra-hepatic metabolism;

however, the drug does not appear to undergo enterohepatic recirculation. Mean plasma

elimination half life of Atorvastatin in human is approximately 14 hours, but the half life of

inhibitory activity for HMG-CoA reductase is 20 - 30 hours due to the contribution of active

metabolites.

INDICATIONS :

Atrovist is indicated in following cases :

- 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) and mixed dyslipidemia (Fredrickson types IIa and IIb)

- As an adjunct to diet for the treatment of patients with elevated serum (TG) levels (Fredrickson

type IV)

- For the treatment of patients with primary dysbetalipoproteinemia (Fredrickson Type III) who

do not respond adequately to diet.

- To reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an

adjunct to other lipid lowering treatments or if such treatments are unavailable.

- Prevention of cardiovascular diseases.

DOSAGE & ADMINISTRATION:

The patients should be placed on a standard cholesterol lowering diet before receiving Atrovist

and should continue on this diet during treatment.

- Primary hypercholesterolemia and mixed Dyslipidemia (Fredrickson Types IIa and IIb):

• The Recommended starting dose is 10 or 20 mg, once daily.

• Patient who require more than 45% LDL-C reduction may be started at 40mg once

daily. The dose should be adjusted after lipid levels analysis within 2 - 4 weeks of

starting treatment. The maximum dose is 80mg once daily.

- Heterozygous familial hypercholesterolemia : The recommended starting dose is

10 mg daily, and the dose should be individualized and adjusted at intervals of 4 weeks to

40mg daily. The maximum dose which can be used is 80mg daily or a bile acid sequestrant

may be combined with 40mg atorvastatin once daily.

- Homozygous familial Hypercholesterolemia : The range of dose 10-80mg daily and should

be used as adjunct to other lipid lowering treatments.

- Prevention of cardiovascular diseases : The primary dose is 10mg/day.

- Dose adjustment for elderly (> 70 years) or renal dysfunction patients is not necessary.

- Pediatric use (age 10 years and above) : the recommended starting dose is 10mg with

titration up to 20mg per day.

- Atorvastatin is not indicated for patients below 10 years.

RESTRICTIONS ON USE :

Contraindications

- Hypersensitivity to Atorvastatin.

- Active liver disease or unexplained persistent elevation of serum transaminases.

- Myopathy.

During pregnancy, breast feeding and women of child bearing potential not using

appropriate contraceptive measures.

Precautions

- Liver enzymes changes generally occur in the first 3 months of treatment with Atorvastatin,

so liver function tests should be monitored. Atorvastatin is contraindicated if transaminase

elevation is persistent.

- Patients how have had haemorrhage stoke or lacunar stroke.

- Uncomplicated myalgia including muscle cramps, has been reported in Atorvastatin

treated patients. Treatment should be discontinued if markedly elevated creatine

phosphokinase levels occur or myopathy is diagnosed or suspected.

- Consumption of alcohol should be avoided.

Use in pregnancy and lactation

Atorvastatin is contraindicated during pregnancy and lactation.

DRUG INTERACTION:

- The risk of myopathy during treatment with Atorvastatin is increased with concurrent

administration of Cyclosporine, fibric acid derivatives, Niacin, macrolide antibiotics

including Erythromycin and azole antifungals.

- When Atorvastatin and antacid containing magnesium and aluminum hydroxides were

coadministered, plasma concentrations of Atorvastatin and its active metabolites

decreased approximately 35%. However, LDL-C reduction was not altered.

- Plasma concentrations of Atorvastatin decreased approximately 25% when coadministrated

with Colestipol. However, LDL-C reduction was greater than when either drug was given

alone.

- When multiple doses of Atorvastatin and Digoxin were coadministered, steady state

plasma Digoxin concentrations increased by approximately 20%.

- Plasma concentrations of Atorvastatin increased approximately 40% with coadministration

of Atorvastatin with Erythromycin due to inhibition of cytochrome P450 3A4.

- Coadministration of Atorvastatin and an oral contraceptives increased AUC values for

Norethindrone and Ethinylestradiol by approximately 30% and 20% respectively.

ADVERSE EFFECTS :

Adverse reactions usually mild and transient. The most frequent adverse effects include:

constipation, flatulence, dyspepsia, abdominal pain, headache, nausea, myalgia, asthenia,

diarrhea and insomnia.

Overdosage :

Specific treatment is not available for Atrovist overdose. Should 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, hemodialysis is not expected to significantly enhance Atorvastatin

clearance.

STORAGE INSTRUCTIONS:

Store below 30°C, in a dry place.

PRESENTATIONS :

Atrovist 10 Tablets : Blister pack of 30 tablets & hospital packs of different sizes.

Atrovist 20 Tablets : Blister pack of 30 tablets & hospital packs of different sizes.

Atrovist 40 Tablets : Blister pack of 10 tablets & hospital packs of different sizes.