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. PHARMACOKINETICS Absorption: Atorvastatin is rapidly absorbed after oral administration, maximum plasma levels occur within 1 to 2 hours. Extent of absorption increases in proportion to atorvastatin dose. The absolute bioavailability of atorvastatin (parent drug) is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is apporximately 30%. Distribution: Mean volume of distribution of atorvastatin is approximately 381 liters. Atorvastatin is >98% bound to plasma proteins. Metabolism: Atorvastatin is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation product. Atorvastatin is metabolized by cytochrome P450 3A4. Excretion: Atorvastatin and its metabolites are eliminated primarily in bile following hepatic metabolism. Mean plasma elimination half-life is approximately 14 hours. Less than 2 % of a dose of atorvastatin is recovered in urine following oral administration.
TCL-R 10 Tablet: Each film-coated tablet contains Atorvastatin Calcium Trihydrate USP equivalent to Atorvastatin 10 mg.
TCL-R 20 Tablet: Each film-coated tablet contains Atorvastatin Calcium Trihydrate USP equivalent to Atorvastatin 20 mg.
TCL-R 40 Tablet: Each film-coated tablet contains Atorvastatin Calcium Trihydrate USP equivalent to Atorvastatin 40 mg.
TCL-R is indicated as an adjunct therapy to diet to:
- Reduce the risk of MI, stroke, revascularization procedures and angina in patients without CHD, but with multiple risk factors.
- Reduce the risk of MI and stroke in patients with type 2 diabetes without CHD, but with multiple risk factors.
- Reduce the risk of non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for CHF, and angina in patients with CHD.
- Reduce elevated total-C, LDL-C, apo B, and TG levels and increase HDL-C in adult patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia.
- Reduce elevated TG in patients with hypertriglyceridemia and primary dysbetalipoproteinemia.
- Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia(HoFH).
- Reduce elevated total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy.
Hyperlipidemia (Heterozygous Familial and nonfamilial) and mixed Dyslipidemia:
The recommended starting dose of TCL-R is 10 or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of TCL-R 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.
Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10-17 years of age): The recommended starting dose of TCL-R is 10 mg/day; the maximum recommended dose is 20 mg/day.
Homozygous Familial Hypercholesterolemia: The dosage of TCL-R in patients with homozygous FH is 10 to 80 mg daily.
Hypersensitivity to any of the ingredients of this medication. Active liver disease which may include unexplained persistent elevations in hepatic transaminase level.
ADVERSE EFFECTS
The most commonly reported adverse reactions (incidence > 2%) in patients treated with atorvastatin in placebo-controlled trials regardless of causality were: nasopharyngitis, arthralgia, diarrhea, pain in extremity, and urinary tract infection
Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase when higher doses are used concomitantly with cyclosporine and strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, HIV protease inhibitors). Predisposing factors include advanced age (> 65), uncontrolled hypothyroidism, and renal impairment. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported.
Advise patients to promptly report to their physician unexplained and/or persistent muscle pain, tenderness, or weakness. Atorvastatin therapy should be discontinued if myopathy is diagnosed or suspected.
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, paresthesia, pancreatitis, hepatitis, cholestatic, anorexia, vomiting, pruritus, rash.
Cyclosporine, HIV protease inhibitors (tipranavir plus ritonavir saquinavir plus ritonavir, hepatitis C protease inhibitor (telaprevir): Avoid Atorvastatin. HIV protease inhibitor (lopinavir plus ritonavir): Use with caution and lowest dose necessary.Clarithromycin,itraconazole, HIV protease inhibitors (saquinavir plus ritonavir,darunavir plus): Do not exceed 20 mg Atorvastatin daily. HIV protease inhibitor (nelfinavir), Hepatitis C protease inhibitor (boceprevir): Do not exceed 40 mg Atorvastatin daily.
Pregnancy & Nursing mother: Pregnancy category X. It is not known whether atorvastatin is excreted into human milk. Women who require Atorvastatin treatment should not breastfeed their infants.
Paediatric Use: Safety and efficacy of atorvastatin have been established in patients 10-17 years of age with heterozygous familial hypercholesterolemia.
Geriatric Use: Efficacy and safety in older patients have been established & therecommended doses are similar to that of adult patients.
Renal Impairment: Renal disease does not affect the plasma concentrations nor LDL-C reduction of atorvastatin; thus, dosage adjustment in patients with renal dysfunction is not necessary.
Hepatic Impairment: Atorvastatin is contraindicated in patients with active liver disease.
TCL-R 10 Tablet: Box containing 30's tablet in alu-alu blister pack.
TCL-R 20 Tablet: Box containing 20's tablet in alu-alu blister pack.
TCL-R 40 Tablet: Box containing 10's tablet in alu-alu blister pack.
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