Santorvastin 40

Atorvastatin.

White round biconvex tablet, odorless, sign Breakline-SB cross.
Each film-coated tablet contains: Atorvastatin Calcium Trihydrate equivalent to Atorvastatin 40 mg.
Excipients/Inactive Ingredients: Calcium Carbonate Heavy, Meglumine, Microcrystalline Cellulose, Hydroxypropyl Cellulose, Crospovidone, Ethyl Alcohol, Silicon Dioxide Colloidal, Magnesium Stearate, Hydroxypropyl Methylcellulose, Polyethylene Glycol 6000, Talc, Titanium Dioxide.

Pharmacology: Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of sterols, including cholesterol.
In patients with homozygous and heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia, and mixed dyslipidemia, Atorvastatin reduces total-C (total cholesterol), LDL-C (low-density lipoprotein cholesterol), and apo B (apolipoprotein B). Atorvastatin also reduces VLDL-C (very-low-density lipoprotein cholesterol) and TG (triglycerides) and produces variable increases in HDL-C (high-density lipoprotein cholesterol).
Atorvastatin lower plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.
Atorvastatin reduces LDL production and the number of LDL particles. Atorvastatin produces a profound and sustained increase in LDL receptor activity coupled with a beneficial change in the quality of circulating LDL particles. Atorvastatin is effective in reducing LDL in patients with homozygous familial hypercholesterolemia, a population that has not normally responded to lipid-lowering medication.
Atorvastatin and some of its metabolites are pharmacologically active in humans. The primary site of action of Atorvastatin is the liver, which is the principal site of cholesterol synthesis and LDL clearance.

SANTORVASTIN 40 is indicated as an adjunct to diet for the reduction of elevated total-C, LDL-C, apo B, and TG in patients with primary hypercholesterolemia, combined (mixed) hyperlipidemia, and heterozygous and homozygous familial hypercholesterolemia when response to diet and other non pharmacological measure are inadequate.
Prevention of Cardiovascular Complication: In hypertensive patient (40 years or older) and dyslipidemia with at least 3 risk factors for future cardiovascular events such as LVH, ECG abnormalities, NIDDM, peripheral vascular disease, post history of cerebrovascular events including transient ischemic attack (TIA) ≥3 months previously, microalbuminuria/proteinuria, smoking (regular smoker within the last year of 20 cigarettes or cigars/week), TC/HDL-C ratio ≥6, and history of coronary artery disease event in a first degree relative before age 55 (males) or 60 (women), SANTORVASTIN 40 is indicated to: Reduce the risk of fatal CHD and non-fatal MI; reduce the risk of stroke; reduce the risk of revascularization procedures and angina pectoris.
Pediatric Patients (10-17 years of age): SANTORVASTIN 40 is indicated 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 hypercholesterolemia if after an adequate trial of diet therapy, the following findings are present: a. LDL-C remains ≥190 mg/dL or; b. LDL-C remains ≥160 mg/dL and: There is a positive family history of premature CVD or two or more other CVD risk factors are present in the pediatric patient.

General: The patients should be placed on a standard cholesterol-lowering diet before receiving SANTORVASTIN 40 and continue on a standard cholesterol-lowering diet during treatment with SANTORVASTIN 40. The usual starting dose is 10 mg once a day. The dosage range is 10 mg to 80 mg once daily. Doses may be given any time of the day, with or without food.
Adults: Primary Hypercholesterolemia and Combined (Mixed) Hyperlipidemia: The majority of patients are controlled with 10 mg SANTORVASTIN 40 once daily. A therapeutic response is evident within 2 weeks, and the maximum response is usually achieved within 4 weeks. The response is maintained during chronic therapy.
Homozygous Familial Hypercholesterolemia: In patients with homozygous familial hypercholesterolemia, most patients responded to 80 mg SANTORVASTIN 40.
Children (10-17 years of age): Heterozygous Familial Hypercholesterolemia: The recommended starting dose of SANTORVASTIN 40 is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patients population). Doses should be individualized according to the recommended goal of therapy. Adjustments should be made at intervals of 4 weeks or more.
Homozygous Familial Hypercholesterolemia: Treatment experience in a pediatric population with doses of SANTORVASTIN 40 up to 80 mg/day is limited.
Patient with Hepatic Insufficiency: In patient with moderate to severe hepatic insufficiency, the therapeutic response to SANTORVASTIN 40 in unaffected but plasma concentration of the drug is greatly increased. Therefore, caution should be exercised in patient who consume substantial quantities of alcohol and/or have a history of liver disease.
Patient with Renal Insufficiency: Renal disease has no influence on plasma concentrations or on the LDL-C reduction of SANTORVASTIN 40. Thus, no dose adjustment is required.
Elderly: Efficacy and safety in older patient (>70 years) using recommended dose is similar to that see in the general population.

There is no specific treatment for Atorvastatin overdose. Should an overdose occur, 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 Atorvastatin clearance.

Atorvastatin is contraindicated in patients who have: Hypersensitivity to any component of this medication.
Active liver disease or unexplained persistent elevations of serum transaminases exceeding three times the upper limit of normal (ULN).
Pregnant, breast-feeding, or of childbearing potential who are not using adequate contraceptive measures. Atorvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards to the fetus.

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 the underlying medical problems.
Patient who develop any signs or symptoms suggesting liver injury should have liver function test performed.
Patients who develop increased transaminase levels should be monitored until the abnormality(ies) resolve(s). Should an increase in ALT or AST of greater than three times the upper limit of normal persist, reduction of dose or withdrawal of Atorvastatin is recommended. Atorvastatin can cause an elevation in transaminases.
Atorvastatin should be use with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease.
Atorvastatin therapy should be discontinued if markedly elevated creatine phosphokinase levels occur.
Myalgia has been reported in Atorvastatin treated patients.
As with other drugs in this class, rare class of rhabdomyolysis with acute renal failure, secondary to myoglobinuria has been reported. Atorvastatin therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders and uncontrolled seizures).
Patient should be advised to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Adolescent females and women of childbearing potential should be counseled on appropriate contraceptive methods while on Atorvastatin therapy.

Atorvastatin is generally well-tolerated. Adverse reactions have usually been mild and transient.
The most frequent adverse effects associated with Atorvastatin therapy in were: Infections and infestations: Nasopharyngitis.
Respiratory, Thoracic and Mediastinal Disorders: Pharyngolaryngeal pain, epistaxis.
Psychiatric Disorders: Insomnia, nightmare.
Nervous System Disorders: Headache.
Gastrointestinal Disorders: Nausea, diarrhea, abdominal pain, dyspepsia, constipation, flatulence.
Musculoskeletal and Connective Tissue Disorders: Myalgia, arthralgia, pain in extremity, musculoskeletal pain, muscle spasms, joint swelling.
Investigations: Liver function test abnormal, blood creatine phosphokinase increased.
General Disorders and Administration Site Conditions: Asthenia.
The following additional adverse effects have been reported in Atorvastatin: Vision blurred; hypoglycemia, hyperglycemia, anorexia; peripheral neuropathy, paresthesia; tinnitus; pancreatitis, vomiting, abdominal discomfort, eructation; hepatitis, cholestatic jaundice; alopecia, pruritus, rash, urticaria; myopathy, myositis, muscle cramps, muscle fatigue, neck pain; impotence; angioneurotic edema, malaise, pyrexia; angina; white blood cells urine positive.
Pediatric Patients (ages 10-17 years): Patients treated with Atorvastatin had an adverse experience profile generally similar to that of patients treated with placebo, the most common adverse experiences observed in both groups, regardless of causality assessment, were infections.
In post-marketing experience, the following additional undesirable effects have been reported: Thrombocytopenia; allergic reactions (including anaphylaxis); tendon rupture; weight gain; hypoesthesia, amnesia, dizziness, dysgeusia; pancreatitis; Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, erythema multiforme, bullous rashes; rhabdomyolysis, immune mediated necrotizing myopathy, myositis, back pain; chest pain, peripheral edema, fatigue.

The risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of Cyclosporine, Fibric Acid derivatives, lipid-modifying doses of Niacin or CYP 3A4 inhibitors (e.g., Erythromycin (see as follows), and Azole antifungals).
Inhibitors of CYP 3A4: Atorvastatin is metabolized by CYP 3A4.
Concomitant administration of Atorvastatin with inhibitors of CYP 3A4 can lead to increases in plasma concentrations of Atorvastatin. The extent of interaction and potentiation of effects depends on the variability of effect on CYP 3A4.
Transporter Inhibitors: Atorvastatin and Atorvastatin metabolites are substrates of the organic anion-transporting polypeptide 1B1 (OATP1B1) transporter. Inhibitors of the OATP1B1 (e.g., Cyclosporine) can increase the bioavailability of Atorvastatin. Concomitant administration of Atorvastatin 10 mg and Cyclosporine 5.2 mg/kg/day resulted in an increase in exposure to Atorvastatin.
Erythromycin/Clarithromycin: Co-administration of Atorvastatin with Erythromycin (500 mg four times daily) or Clarithromycin (500 mg twice daily) known inhibitors of CYP 3A4, was associated with higher plasma concentrations of Atorvastatin.
Protease Inhibitors: Co-administration of Atorvastatin with protease inhibitors, known inhibitors of CYP 3A4, was associated with increased plasma concentrations of Atorvastatin.
Diltiazem Hydrochloride: Co-administration of Atorvastatin (40 mg) with Diltiazem (240 mg) was associated with higher plasma concentrations of Atorvastatin.
Cimetidine: An Atorvastatin interaction study with Cimetidine was conducted, and no clinically significant interactions were seen.
Itraconazole: Concomitant administration of Atorvastatin (20-40 mg) and Itraconazole (200 mg) was associated with an increase in Atorvastatin AUC.
Grapefruit Juice: Contains one or more components that inhibit CYP 3A4 and can increase plasma concentrations of Atorvastatin, especially with excessive grapefruit juice consumption (>1.2 L/day).
Inducers of CYP 3A4: Concomitant administration of Atorvastatin with inducers of CYP 3A4 (e.g., Efavirenz, Rifampin) can lead to variable reductions in plasma concentrations of Atorvastatin. Due to the dual interaction mechanism of Rifampin (CYP 3A4 induction and inhibition of hepatocyte uptake transporter OATP1B1), simultaneous coadministration of Atorvastatin with Rifampin is recommended, as delayed administration of Rifampin has been associated with a significant reduction in Atorvastatin plasma concentrations.
Antacids: Co-administration of Atorvastatin with an oral antacid suspension containing Magnesium and Aluminium Hydroxides decreased Atorvastatin plasma concentrations; however, LDL-C reduction was not altered.
Antipyrine: Because Atorvastatin does not affect the pharmacokinetics of antipyrine, interactions with other drugs metabolized via the same cytochrome isozymes are not expected.
Colestipol: Plasma concentrations of Atorvastatin were lower when Colestipol was administered with Atorvastatin. However, lipid effects were greater when Atorvastatin and Colestipol were co-administered than when either drug was given alone.
Digoxin: When multiple doses of Digoxin and 10 mg Atorvastatin were co-administered, steady-state plasma Digoxin concentrations were unaffected. However, Digoxin concentrations increased following administration of Digoxin with 80 mg Atorvastatin daily. Patients taking Digoxin should be monitored appropriately.
Azithromycin: Co-administration of Atorvastatin (10 mg once daily) with Azithromycin (500 mg once daily) did not alter the plasma concentrations of Atorvastatin.
Oral contraceptives: Co-administration of Atorvastatin with an oral contraceptive containing Norethindrone and Ethinyl Estradiol increased the area under the concentration vs. time curve (AUC). These increases should be considered when selecting an oral contraceptive for a woman taking Atorvastatin.
Warfarin: An Atorvastatin interaction studies with Warfarin was conducted, and no clinically significant interaction were seen.
Colchicine: Although interaction studies with Atorvastatin and Colchicine have not been conducted, cases of myopathy have been reported with Atorvastatin co-administered with Colchicine, and caution should be exercised when prescribing Atorvastatin with Colchicine.
Amlodipine: In a drug-drug interaction study in healthy subjects, co-administration of Atorvastatin 80 mg with Amlodipine 10 mg resulted in an increase in exposure to Atorvastatin which was not clinically meaningful.
Fusidic Acid: Although interaction studies with Atorvastatin and Fusidic Acid have not been conducted, there is an increased risk of rhabdomyolysis in patients receiving a combination of statins, including Atorvastatin, and Fusidic Acid. The mechanism of this interaction is not known. In patients where the use of systemic Fusidic Acid is considered essential, statin treatment should be discontinued throughout the duration of Fusidic Acid treatment. Statin therapy may be reintroduced seven days after the last dose of Fusidic Acid.

Store below 30°C.

Dyslipidaemic Agents

C10AA05 - atorvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.

K