📌 COMPOSITION

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

📌 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 can be 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. The mean plasma elimination half-life of Atorvastatin in humans 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 the 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 triglyceride 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

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 mg or 20 mg once daily.
  • Patients who require more than 45% LDL-C reduction may be started at 40 mg once daily. The dose should be adjusted after lipid level analysis within 2-4 weeks of starting treatment. The maximum dose is 80 mg 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 up to 40 mg daily. The maximum dose which can be used is 80 mg daily, or a bile acid sequestrant may be combined with 40 mg Atorvastatin once daily.
• Homozygous familial hypercholesterolemia: The dose range is 10-80 mg daily, and it should be used as an adjunct to other lipid-lowering treatments.
• Prevention of cardiovascular diseases: The starting dose is 10 mg/day.
• Dose adjustment for elderly patients (> 70 years) or those with renal dysfunction is not necessary.
• Pediatric use (age 10 years and above): The recommended starting dose is 10 mg with titration up to 20 mg per day.
• Atorvastatin is not indicated for patients below 10 years of age.

📌 RESTRICTIONS ON USE

Contraindications

• Hypersensitivity to Atorvastatin.
• Active liver disease or unexplained persistent elevation of serum transaminases.
• Myopathy.
• During pregnancy, breast-feeding, and in women of childbearing potential not using appropriate contraceptive measures.

Precautions

• Liver enzyme 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 who have had a haemorrhagic stroke 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 if myopathy is diagnosed or suspected.
• Consumption of alcohol should be avoided.

Use in Pregnancy and Lactation

Atorvastatin is contraindicated during pregnancy and lactation.

📌 DRUG INTERACTIONS

• 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 antacids containing magnesium and aluminium hydroxides were coadministered, plasma concentrations of Atorvastatin and its active metabolites decreased by approximately 35%. However, LDL-C reduction was not altered.
• Plasma concentrations of Atorvastatin decreased by approximately 25% when coadministered 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 by approximately 40% with coadministration of Atorvastatin and Erythromycin due to inhibition of cytochrome P450 3A4.
• Coadministration of Atorvastatin and an oral contraceptive increased AUC values for Norethindrone and Ethinylestradiol by approximately 30% and 20%, respectively.

📌 ADVERSE EFFECTS

Adverse reactions are usually mild and transient. The most frequent adverse effects include: constipation, flatulence, dyspepsia, abdominal pain, headache, nausea, myalgia, asthenia, diarrhoea and insomnia.

📌 OVERDOSAGE

No specific treatment is 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, haemodialysis is not expected to significantly enhance Atorvastatin clearance.

📌 STORAGE INSTRUCTIONS

Store below 30°C in a dry place.

📌 PHARMACEUTICAL FORMS

• Atrovist 10 Tablets: Blister pack of 30 tablets and hospital packs of different sizes.
• Atrovist 20 Tablets: Blister pack of 30 tablets and hospital packs of different sizes.
• Atrovist 40 Tablets: Blister pack of 10 tablets and hospital packs of different sizes.