Category: Antihyperlipidemic   (USP DI 2001)
Composition:
Each film coated tablet contains atorvastasin calcium trihydrate, equivalent to 10 or 20 or 40 mg atrovastatin.   (PDR 2002)
Chemistry:
Atorvastatin is an inhibitor of 3-hydroxy-3 methyl- glutaryl-coenzyme A(HMG-CoA) reductase. Atorvastatin calcium is [R-(R*, R*)]-2-(4-flurophenyl) - b, d - dihydroxy-5-(1-methylethyl)-3-phenyl- 4-[(phenylamino) carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2:1) trihydrate.
The empirical formula of atorvastatin calcium is (C33H34FN2O5)2 Ca.3H2O.
Its structural formula is as follow:

Molecular weight=1209.3

Mechanism of action:
The active beta-hydroxy acid form of the 3-hydroxy-3-methylglutaryl co-enzyme A(HMG-CoA) reductase inhibitors competitively inhibits the enzyme HMG-CoA reductase. Atorvastatin is administered in the active (open acid) form.
Inhibition of HMG-CoA reductase prevents conversion of HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis, the primary site of action of HMG-CoA reductase inhibitors in the liver. Inhibition of cholesterol synthesis in the liver leads to upregulation of LDL receptors and an increase in catabolism of LDL cholesterol. There may also be some reduction in LDL production as a result of inhibition of hepatic synthesis of very low-density lipoprotein (VLDL), the precursor of LDL. HMG-CoA reductase inhibitions reduce LDL cholesterol, VLDL cholesterol, and to a lesser extent, plasma triglyceride concentrations and slightly increase high density lipoprotein HDL concentration.   (USP DI 2001)
Pharmacokinetics:
Absorption: Rapidly   (USP DI 2001)
Protein binding:
very high (>_ 98%)   (USP DI 2001)
Biotransformation:
Administered in active (open acid) form. Biotransformation by ortho-and parahydroxy lation and beta-oxidation.
Ortho-and parahydroxylated metabolites are pharmacologically active. Their  in vitro inhibition of HMG-CoA reductase activity is equivalent to the parent compound.   (USP DI 2001)
Elimination half life:
Approximately 14 hours.   (USP DI 2001)
Time to peak concentration:
About 1-2 hours   (USP DI 2001)
Elimination:
Fecal (biliary): Primary route of elimination(USP DI 2001)
Renal: Less than 2%   (USP DI 2001)
Indications:
Atorvastatin is indicated:
1- As an adjunct to diet to reduce elevated total- C, LDL- C apo B, and TG levels and to increase HDL-C in patient with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb
2- As an adjunct to diet for the treatment of patients with elevated serum TG levels (Fredrickson type IV)
3-For the treatment of patients with primary dysbetalipoproteinemia (Fredrickson Type III) who did not respond edequately to diet.
4- To reduce total-c and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable.   (PDR 2002)
Contraindications:
1-Active liver disease or unexplained persistent elevations of serum transaminases.
2- Hypersensitivity to any component of this medication.   (PDR 2002)
3- Pregnancy and lactation
4- Alcoholism, active or in remission
5- Organ transplant with immunosuppressant therapy
6- Sensitivity to any HMG- CoA reductase inhibitor.
7- Serious conditions predisposing to the development of renal failure secondary to rhabdomyolysis.   (USP DI 2001)
Warning:
1- Liver dysfunction: Atortvastatin has been associated with biochemical abnormalities of liver function.
2- Skeletal muscle: Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with atorvastatin  and with other drugs in this class. Uncomplicated myalgia has been reported in atorvastatin  treated patients.
Atorvastatin therapy should be temporaily withheld or discountinued in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development or renal failure secondary to rhabdo myolysis (eg, severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, uncontrolled seizures.)   (PDR 2002)
Precautions:
Before instituting therapy with atorvastatin, an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, and weight reduction in obese patients and to treat other underlying medical problems.
Endocrine function: Atorvastatin does not reduce basal plasma cortisol concentration or impair adrenal reserve. Caution should be exercised if an HMG-CoA reductase inhibitor is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine. CNS toxicity, carcinogenicity, mutagenicity and impairment of fertility.   (PDR 2002)
Pregnancy:
HMG-CoA reductase inhibitors are not recommended for use during pregnancy or in women, who plan to become pregnant in the near future.
FDA pregnancy Category X.   (USP DI 2001)
Breast-feeding:
Use of HMG-CoA reductase inhibitors while breast-feeding is not recommended, becuase of the potential for serious adverse effects in nursing infants.    (USP DI 2001)
Drug interactions:
1- Warfarin 2- Antacids
3- Oral contraceptives 4- Digoxin (USP DI 2001)
5- Antipyrine 6- Colestipol
7- Cimetidine 8- Erythromycin (PDR 2002)
Adverse reactions:
Those indicating need for medical attention:
Incidence less frequent or rare:
Myalgia, myositis, rhabdomylysis.
Note: Rhabdomyolysis may lead to renal failure. Incidence may be increased in patient treated with immunosuppressants, gemfibrozil, erythromycin or niacin. Onset may occur weeks to months after initiation of treatment. Patients should be advised to report immediately to physician any unexplained muscle pain, tenderness or weakness, especially if it is accompanied by malaise of fever.
Those indicating need for medical attention only if they continue or are bothersome.
Incidence more frequent:
Constipation, diarrhea, gas, heartburn, stomach pain, dizziness, headache, nausea, skin rash.
Incidence rare:
Impotence, insomina.   (USP DI 2001)
Before using this medication:
Diet as preferred therapy, importance of following prescribed diet.
Conditions affecting use, especially:
1- Sensitivity to any HMG-CoA reductase inhibitor.
2- Pregnancy
3- Breast- feeding
4- Other medications, especially cyclosporine, gemfibrozil, niacin, digoxin, oral contraceptive, grapefruit juice in large amounts.
5- Other medical problems, especially, active hepatic disease, hypotension, major surgery, organ transplant with immunosuppressant therapy, severe infection, severe metabolic, endocrine, or electrolyte disorders, trauma or uncontrolled seizures.   (USP DI 2001)
Proper use of this medication:
1- Importance of not taking more or less medication than the amount prescribed.
2- Compliance with prescribed diet.
3- Proper dosing
Missed dose: Taking as soon as possible, not taking if almost time for next dose; not doubling doses.
4- Proper storage: Importance of not taking atorvastatin with grapefruit juice in large amount.
Precautions while using this medication:
1- Importance of close monitoring by physician.
2- Notifying physician immediately if pregnancy is suspected.
3- Checking with physician before discontinuing medications; blood lipid levels may increase significantly
4- Caution if any kind of surgery ( including dental surgary) or emergency treatment is required.   (USP DI 2001)
Administration and dosage:
Usual adult and adolescent dose:
Antihyperlipidemic: Heterozygous familial and nonfamilial hypercholesterolemia and mixed dyslipidemia:
Initial oral 10 mg (base) once a day. The dosage can adjusted after assessing treatment response in 2 to 4 weeks.
Maintenance: Oral , 10 to 80 mg (base) once a day.
Homozygous familial hypercholesterolemia:
Oral 10 to 80 mg a day
Note: Atorvastatin should be used in these patients as an adjunct to other lipid lowering treatments such as LDL apheresis or if such treatments are unavailable.
Usual pediatric dose:
Dosage has not been established.   (USP DI 2001)
Packaging and storage:
Store at controlled room temperature 20-25˚C.