TCL-R

Atorvastatin

Description:

TCL-R is a preparation of Atorvastatin, which acts as a cholesterol lowering agent. TCL-R inhibits 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase, an enzyme that catalyzes the biosynthesis of cholesterol. The enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the synthesis of cholesterol.

Composition:

TCL-R 10 mg Tablet: Each film-coated tablet contains Atorvastatin Calcium Trihydrate equivalent to Atorvastatin INN 10 mg.

TCL-R 20 mg Tablet: Each film-coated tablet contains Atorvastatin Calcium Trihydrate equivalent to Atorvastatin INN 20 mg.

Mechanism of action:

HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate which is the major rate limiting step in the cholesterol synthesis pathway. The main mechanism of reduction of low density lipoprotein (LDL) cholesterol is that, following inhibition of HMG-CoA reductase activity, the LDL receptor density on the liver cell is increased and this leads to an increased removal of LDL cholesterol from the plasma and increased catabolism of LDL cholesterol. In addition there is a reduction in very low-density lipoprotein (VLDL) cholesterol and reduced formation of LDL from VLDL.

Pharmacokinetics:

TCL-R is rapidly absorbed after oral administration, maximum plasma levels occur within 1 to 2 hours. The absolute bioavailability of Atorvastatin (parent drug) is approximately 12% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. Although food reduces the rate and extent of drug absorption by approximately 25% & 9% respectively. Plasma TCL-R concentration is lower following evening drug administration compared with the morning administration. Atorvastatin is approximately 98% bound to plasma proteins. Atrovastin and its metabolites are eliminated primarily in bile following hepatic and/or extra hepatic metabolism, however the drug does not appear to undergo enterohepatic circulation. The mean plasma elimination half-life of Atorvastatin in human is approximately 14 hours, but the half-life of inhibitory activity of HMG-CoA reductase is 20 to 30 hours due to the contribution of active metabolites. Less than 2% of a dose of Atorovastatin is recovered in urine following oral administration.

Indications:

1. In patients unresponsive to diet and other non-pharmacological measures, TCL-R is indicated for the reduction of elevated total cholesterol, LDL-cholesterol, apolipoprotein B and triglycerides.

2. In patients with primary hypercholesterolemia, heterozygous familial hypercholesterolaemia or mixed dyslipidaemia.

3. In patients with elevated serum triglyceride levels.

4. In patients with primary dysbetalipoproteinaemia.

5. In patients with homozygous familial hypercholesterolaemia as an adjunct to other lipid lowering treatments.

Dosage & Administration :

Adults:

The patients should be placed on a standard cholesterol-lowering diet before receiving Atorvastatin and should continue on this diet during treatment with TCL-R.

Hypercholesterolaemia and mixed dyslipidaemia: The recommended starting dose of TCL-R is 10 mg daily. The dosage range is 10 to 80 mg once daily. TCL-R can be administered as a single dose at any time of the day with or without food.

Homozygous Familial Hypercholesterolaemia (FH): The dosage of TCL-R in-patients with homozygous familial hypercholesterolaemia (FH) is 10 to 80 mg daily.

Overdosage:

There is no specific treatment for TCL-R overdosage. In the event of an overdosage, the patient should be treated symptomatically and general supportive measures instituted as required. Due to excessive drug binding to plasma proteins, haemodialysis is not expected to significantly enhance Atrovastatin clearance. Liver function tests and serum CPK levels should be monitored.

Adverse effects:

Atorvastatin is generally well tolerated. Side effects reported commonly include constipation, flatulence, dyspepsia, abdominal pain, headache, nausea, myalgia, diarrhoea, asthenia and insomnia. Others include muscle cramps, myositis, myopathy, paresthesia, peripheral neuropathy, pancreatitis, hepatitis, cholestatic jaundice, anorexia, vomiting, pruritus, rash, impotence, hyperglycemia and hypoglycemia  etc. Chest pain, dizziness, angina, and allergic reactions have been reported in isolated cases.

Contraindications:

Hypersensitivity to any of the ingredients of this medication, active liver disease or unexplained persistent elevations of serum transaminases, pregnancy and breast feeding and in woman of child-bearing potential not using contraception.

Precaution: HMG-CoA reductase inhibitors, like some other lipid lowering therapies, have been associated with biochemical abnormalities of liver function. liver function tests should be performed before treatment starts, at 6 weeks and 12 weeks after initiation of therapy or elevation in dose and periodically thereafter and in patients who show sign and symptoms of liver injury. Drug doses should be reduced or therapy discontinued if persistent elevation occur 3-times the upper limit of normal. TCL-R should be used with caution in patients with a history of liver disease or alcoholism. Uncomplicated myalgias have been reported. Patients with sign and symptoms of myopathy should have their creatine phosphokinase (CPK) levels monitored. TCL-R should be discontinued if CPK levels are markedly or persistently raised or myopathy is diagnosed or suspected. Rhabdomyolysis with renal dysfunction secondary to myoglobinuria has been reported with other drugs of this class.   

Use in pregnancy & lactation:

HMG-CoA reductase inhibitors are not recommended for use during pregnancy. An interval of 1 month should be allowed from stopping an Atorvastatin treatment to conception in the event of planning a pregnancy. Use of HMG-CoA reductase inhibitors during breast-feeding is not recommended because of the potential for serious adverse effects in nursing infants.

Pediatrics : Safety and efficacy of Atorvastatin have not been established in children.

Geriatrics : Efficacy and safety in older patients have been established & the recommended doses are similar to that of adult patients.

 Drug Interaction :

Erythromycin, oral contraceptives, colestipol, digoxin, cyclosporine, fibric acid derivatives, azole, antifungals, niacin, antacid, warfarin, cimetidine.

Packing:

TCL-R 10 mg Tablet: Each box contains 3x10's in blister pack.

TCL-R 20 mg Tablet: Each box contains 1x10's in blister pack.