ATORVATIN ( FILM COATED TABLETS)
ATORVATIN (Atorvastatin calcium) is a synthetic
Mechanism of Action:
Atorvastatin is a selective, competitive inhibitor of
HMG-CoA reductase, the rate-limiting enzyme that
converts 3-hydroxy-3-methyl-glutaryl-coenzyme A to
mevalonate, a precursor of sterols, including
cholesterol. Clinical and pathologic studies show that
elevated plasma levels of total cholesterol (total-C),
LDL-cholesterol (LDL-C), and apolipoprotein B (apo B)
promote human atherosclerosis and are risk factors for
developing cardiovascular disease, while increased
levels of HDL-C are associated with a decreased
Atorvastatin is rapidly absorbed after oral
administration; maximum plasma concentrations occur
within 1 to 2 hours. Atorvastatin is 98% bound to plasma
proteins. Atorvastatin is extensively metabolized to
ortho- and parahydroxylated derivatives and various
beta-oxidation products. Atorvastatin and its
metabolites are eliminated primarily in bile following
hepatic and/or extrahepatic metabolism. 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 to 30 hours. Less
than 2% of a dose of atorvastatin is recovered in urine
following oral administration.
1. As an adjunct to diet to reduce elevated total-C, LDL-C,
apo B, and TG levels and
to increase HDL-C in patients with primary
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
do not respond adequately 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
5. As an adjunct to diet to reduce total-C, LDL-C, and
apo B levels in boys and postmenarchal girls, 10 to 17
years of age, with heterozygous familial
ATORVATIN is contraindicated in active liver disease or
unexplained persistent elevations of serum transaminases.
And also contraindicated in hypersensitivity to any
component of this medication.
Pregnancy and Lactation:
ATORVATIN may cause fetal harm when administered to
pregnant women. Therefore, HMG-CoA reductase inhibitors
are contraindicated during pregnancy and in nursing
mothers. If the patient becomes pregnant while taking
this drug, therapy should be discontinued.
NCEP Treatment Guidelines: LDL-C Goals
and Cutpoints for Therapeutic Lifestyle
Changes and Drug Therapy in Different Risk
LDL Level at Which to Consider Drug
LDL Level at Which to consider Drug
CHD or CHD risk equivalents
(10 years risk > 20%)
(100-129: drug optional)
(10 years risk £ 20 %)
10 year risk 10% -20% ³ 130
10 years risk < 10%: ³ 160
0-1 Risk factor
(160-189: LDL- lowering drug optional)
CHD: Coronary Heart Disease
It is recommended that liver function tests be performed
prior to and at 12 weeks following both the initiation
of therapy and any elevation in dose, and periodically (eg,
ATORVATIN should be used with caution in patients who
consume substantial quantities of alcohol and/or have a
history of liver disease.
Rhabdomyolysis with acute renal failure secondary to
myoglobinuria has been reported with ATORVATIN.
Uncomplicated myalgia has been reported in atorvastatin-treated
ATORVATIN therapy should be temporarily withheld or
discontinued in any patient with an acute, serious
condition suggestive of a myopathy or having a risk
factor predisposing to the development of renal failure
secondary to rhabdomyolysis (eg, severe acute infection,
hypotension, major surgery, trauma, severe metabolic,
endocrine and electrolyte disorders, and uncontrolled
Before instituting therapy with ATORVATIN, an attempt
should be made to control hypercholesterolemia with
appropriate diet, exercise, and weight reduction in
Patients should be advised to report promptly
unexplained muscle pain, tenderness, or weakness,
particularly if accompanied by malaise or fever.
The risk of myopathy during treatment with ATORVATIN is
increased with concurrent administration of
cyclosporine, fibric acid derivatives, niacin (nicotinic
acid), erythromycin and azole antifungals.
Antacid: When ATORVATIN and antacid were
coadministered, plasma concentrations of ATORVATIN
decreased approximately 35%. However, LDL-C reduction
was not altered.
Colestipol: Plasma concentrations of ATORVATIN
decreased approximately 25% when colestipol and
ATORVATIN were coadministered. However, LDL-C reduction
was greater when ATORVATIN and colestipol were
coadministered than when either drug was given alone.
Cimetidine: ATORVATIN plasma concentrations and
LDL-C reduction were not altered by coadministration of
Digoxin: When multiple doses of ATORVATIN and
digoxin were coadministered, steady-state plasma digoxin
concentrations increased by approximately 20%. Patients
taking digoxin should be monitored appropriately.
Warfarin: ATORVATIN had no clinically significant
effect on prothrombin time when administered to patients
receiving chronic warfarin treatment.
Oral contraceptives: Coadministration of
ATORVATIN and oral contraceptive increased AUC values
for norethindrone and ethinyl estradiol by approximately
30 % and 20 %>
Erythromycin: In healthy individuals, plasma
concentrations of atorvastatin increased approximately
40% with coadministration of atorvastatin and
erythromycin, a known inhibitor of cytochrome P450 3A4.
HMG-CoA reductase inhibitors interfere with cholesterol
synthesis and theoretically might blunt adrenal and/or
gonadal steroid production. Clinical studies have shown
that atorvastatin does not reduce basal plasma cortisol
concentration or impair adrenal reserve. The effects of
HMG-CoA reductase inhibitors on male fertility have not
been studied in adequate numbers of patients. The
effects, if any, on the pituitary-gonadal axis in
premenopausal women are unknown. 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.
The most frequent adverse events thought to be related
to ATORVATIN were constipation, flatulence, dyspepsia,
and abdominal pain.
Body as a Whole: Chest pain , face edema, fever,
neck rigidity, malaise, photosensitivity reaction,
Digestive System: Nausea , gastroenteritis, liver
function tests abnormal, colitis, vomiting, gastritis,
dry mouth, rectal hemorrhage, esophagitis, eructation,
glossitis, mouth ulceration, anorexia, increased
appetite, stomatitis, biliary pain, chelitis, duodenal
ulcer, dysphagia, enteritis, melena, gum hemorrhage,
stomach ulcer, tenesmus, ulcerative stomatitis,
hepatitis, pancreatitis, cholestatic jaundice.
Respiratory System: Bronchitis, rhinitis ,
pneumonia, dyspnea, asthma, epistaxis.
Nervous System: Insomnia, dizziness , paresthesia,
somnolence, amnesia, abnormal dreams, libido decreased,
emotional lability, incoordination, peripheral
neuropathy, torticollis, facial paralysis, hyperkinesia,
depression, hypesthesia, hypertonia.
Musculoskeletal System: Arthritis , leg cramps,
bursitis, tenosynovitis, myasthenia, tendinous
Skin and Appendages: Pruritus, contact
dermatitis, alopecia, dry skin, sweating, acne,
urticaria, eczema, seborrhea, skin ulcer.
Urogenital System: Urinary tract infection ,
urinary frequency, cystitis, hematuria, impotence,
dysuria, kidney calculus, nocturia, epididymitis,
fibrocystic breast, vaginal hemorrhage, albuminuria,
breast enlargement, metrorrhagia, nephritis, urinary
incontinence, urinary retention, urinary urgency,
abnormal ejaculation, uterine hemorrhage.
Special Senses: Amblyopia, tinnitus, dry eyes,
refraction disorder, eye hemorrhage, deafness, glaucoma,
parosmia, taste loss, taste perversion.
Cardiovascular System: Palpitation,
vasodilatation, syncope, migraine, postural hypotension,
phlebitis, arrhythmia, angina pectoris, hypertension.
Metabolic and Nutritional Disorders: Peripheral edema ,
hyperglycemia, creatine phosphokinase increased, gout,
weight gain, hypoglycemia.
Hemic and Lymphatic System: Ecchymosis, anemia,
lymphadenopathy, thrombocytopenia, petechia.
There is no specific treatment for ATORVATIN overdosage.
In the event of an overdose, the patient should be
treated symptomatically, and supportive measures
instituted as required. Due to extensive drug binding to
plasma proteins, hemodialysis is not expected to
significantly enhance ATORVATIN clearance.
Store at 20°C to 25°C
Keep away of reach of children.