LIPITO-MED 40

  • Therapeutic Category
    • CARDIOVASCULAR DRUGS
    • LIPID - LOWERING DRUGS
  • Pharmaceutical Form : Film coated tablets
  • Composition : Atorvastatin ( Calcium ) 40 mg / Ctd.Tab
  • Active Substance : Atorvastatin

CLINICAL PHARMACOLOGY:

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 cardiovascular risk.

Pharmacokinetics

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.

INDICATIONS:

  1. 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 hypercholesterolemia (heterozygous familial and nonfami lial) and mixed dyslipidemia ( Fredrickson Types IIa and IIb).
    2. As an adjunct to diet for the treatment of patients with elevat ed serum TG levels ( Fredrickson Type IV).
    3. For the treatment of patients with primary dysbetalipoprotei nemia ( 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 unavailable.
    Therapy with lipid-altering agents should be a component of mul tiple-risk-factor intervention in individuals at increased risk
    for atherosclerotic vascular disease due to hypercholesterolemi a. Lipid-altering agents should be used in addition to a diet
    restricted in saturated fat and cholesterol only when the respo nse to diet and other nonpharmacological measures has been
    inadequate
    5.Prevention of cardiovascular disease : Prevention of cardiova scular events in patients estimated to have a high risk for a fi rst
    cardiovascular event, as an adjunct to correction of other risk factors.

CONTRAINDICATION:
LIPITO-MED 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:

LIPITO-MED 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.

Lactation:

Because of the potential for adverse reactions in nursing infants, women taking LIPITO-MED should not breast-feed.

WARNINGS:

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, semiannually) thereafter.

LIPITO-MED 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 LIPITO-MED. Uncomplicated myalgia has been reported in atorvastatin-treated patients.

LIPITO-MED 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 seizures).

INFORMATION FOR PATIENTS:

Before instituting therapy with LIPITO-MED, an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, and weight reduction in obese patients.

Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.

DRUG INTERACTION

The risk of myopathy during treatment with LIPITO-MED is increased with concurrent administration of cyclosporine, fibric acid derivatives, niacin (nicotinic acid), and erythromycin and azole antifungals.

Antacid: When LIPITO-MED and antacid were co-administered, plasma concentrations of LIPITO-MED decreased approximately 35%. However, LDL-C reduction was not altered.

Colestipol: Plasma concentrations of LIPITO-MED decreased approximately 25% when colestipol and LIPITO-MED were coadministered. However, LDL-C reduction was greater when LIPITO-MED and colestipol were coadministered than when either drug was given alone.

Cimetidine: LIPITO-MED plasma concentrations and LDL-C reduction were not altered by coadministration of cimetidine.

Digoxin: When multiple doses of LIPITO-MED and digoxin were coadministered, steady-state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately.

Warfarin: LIPITO-MED had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin treatment.

Oral contraceptives: Coadministration of LIPITO-MED 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.

Endocrine Function

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.

ADVERSE REACTIONS:

The most frequent adverse events thought to be related to LIPITO-MED were constipation, flatulence, dyspepsia, and abdominal pain.

Body as a Whole: Chest pain, face edema, fever, neck rigidity, malaise, photosensitivity reaction, generalized edema.

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 contracture, myositis.

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.

OVERDOSAGE:

There is no specific treatment for LIPITO-MED 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 LIPITO-MED clearance.

DOSAGE AND ADMINISTRATION

Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)

The recommended starting dose of LIPITO-MED 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 LIPITO-MED is 10 to 80 mg once daily. LIPITO-MED can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of LIPITO-MED should be individualized according to patient characteristics such as goal of therapy and response. After initiation and/or upon titration of LIPITO-MED, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly.

Since the goal of treatment is to lower LDL-C, the NCEP recommends that LDL-C levels be used to initiate and assess treatment response. Only if LDL-C levels are not available, should total-C be used to monitor therapy.

Homozygous Familial Hypercholesterolemia

The dosage of Lipitor in patients with homozygous FH is 10 to 80 mg daily. Lipitor should be used as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) in these patients or if such treatments are unavailable.

Concomitant Therapy

Atorvastatin may be used in combination with a bile acid binding resin for additive effect. The combination of HMG-CoA reductase inhibitors and fibrates should generally be avoided

Dosage in Patients with Renal Insufficiency

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

Storage:

Store at 20°C to 25°C

Keep away of reach of children

Packing: Box of 20 – 30 coated Tablet