Rostatin

Rostatin

rosuvastatin

Manufacturer:

Atlantic Lab

Distributor:

Atlantic Pharma

Marketer:

Atlantic Pharma
Full Prescribing Info
Contents
Rosuvastatin.
Description
Each tablet contains 10 mg and 20 mg rosuvastatin calcium equivalent to rosuvastatin, respectively.
Action
Pharmacology: Pharmacodynamics: Rosuvastatin is a lipid regulating drug; it is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate determining enzyme for cholesterol synthesis. Inhibition of HMG-CoA reductase leads to reduced cholesterol synthesis in the liver and lower intracellular cholesterol concentrations; this stimulates an increase in low­-density-lipoprotein (LDL)-cholesterol receptors on hepatocyte membranes, thereby increasing the clearance of LDL from the circulation. HMG-CoA reductase inhibitors (also called statins) reduce total cholesterol, LDL­-cholesterol, and very-low-density lipoprotein (VLDL)-cholesterol concentrations in plasma.
They also tend to reduce triglycerides and to increase high-density lipoprotein (HDL)-cholesterol concentrations.
Pharmacokinetics: Onset of action: Within 1 week; maximal at 4 weeks.
Distribution: Vd: 134 L.
Protein binding: 88%.
Metabolism: Hepatic (10%), via CYP2C9 (1 active metabolite identified: N-desmethyl rosuvastatin, one-sixth to one-half the HMG-CoA reductase activity of the parent compound).
Bioavailability: 20% (high first-pass extraction by liver).
Asian patients have been noted to have increased bioavailability.
Half-life elimination: 19 hours.
Time to peak, plasma: 3-5 hours.
Excretion: Feces (90%), primarily as unchanged drug.
Indications/Uses
Children and adolescents 10 - 17 years: Heterozygous familial hypercholesterolemia (HeFH).
Adults: Used with dietary therapy for hyperlipidemia to reduce elevations in total cholesterol (TC), LDL-cholesterol, apolipoprotein B (apo B) in patients with primary hypercholesterolemia (type IIa including heterozygous familial hypercholesterolemia), mixed dyslipidemia (type IIb), or homozygous familial hypercholesterolemia who have not responded adequately to diet and other appropriate measures. It may be used to reduce the progression of atherosclerosis in patients with elevated total- or LDL-cholesterol concentrations, and also for the primary prevention of cardiovascular disease in those at high risk.
Dosage/Direction for Use
Recommended Dose: Doses should be individualized according to the baseline LDL-cholesterol levels, the recommended goal of therapy, and patient response; adjustments should be made at intervals of 2-4 weeks.
Children: 10-17 years (female >1 year postmenarche): HeFH: 5-20 mg once daily; maximum: 20 mg/day.
Adults: Initial dose: General dosing: 10 mg once daily; 20 mg once daily may be used in patients with severe hyperlipidemia (LDL >190 mg/dL) and aggressive lipid targets.
Conservative dosing: Patients requiring less aggressive treatment or predisposed to myopathy (including patients of Asian descent): 5 mg once daily.
Titration: After 2 weeks, may be increased by 5-10 mg once daily; dosing range: 5-40 mg/day (maximum dose: 40 mg once daily).
Note: The 40 mg dose should be reserved for patients who have not achieved goal cholesterol levels on a dose of 20 mg/day, including patients switched from another HMG-CoA reductase inhibitor.
Homozygous familial hypercholesterolemia (FH): Initial: 20 mg once daily (maximum dose: 40 mg/day).
Dosage adjustment with concomitant medications: Cyclosporine: Rosuvastatin dose should not exceed 5 mg/day.
Gemfibrozil: Avoid concurrent use; if unable to avoid concurrent use, rosuvastatin dose should not exceed 10 mg/day.
Atazanavir/ritonavir or lopinavir/ritonavir: Rosuvastatin dose should not exceed 10 mg/day.
Dosage adjustment in renal impairment: Mild to moderate impairment: No dosage adjustment required.
Clcr <30 ml/minute/1.73 m2: Initial: 5 mg/day; do not exceed 10 mg once daily.
Dosage adjustment in hepatic impairment: Active hepatic disease, including unexplained persistent transaminase elevations: Use is contraindicated.
Mode of Administration: May be administered with or without food. May be taken at any time of the day.
Overdosage
Significant toxicity has not been reported after acute overdose. Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with vomiting or diarrhea.
Hemodialysis is not expected to significantly enhance the clearance of the drug due to extensive protein binding and large volumes of distribution.
Contraindications
Hypersensitivity to rosuvastatin or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases (>3 times ULN); pregnancy; breast-feeding.
Special Precautions
Hepatic Effects: Therapy with rosuvastatin and other statins has been associated with increases in serum aminotransferase (transaminase) concentrations (e.g., AST (SGOT), ALT (SGPT)). Therefore, the manufacturer recommends that liver function tests be performed before and at 12 weeks after initiation of rosuvastatin therapy or any increase in dosage and periodically (e.g., semiannually) thereafter. Patients who develop increased serum transaminase concentrations or manifestations of liver disease should have frequent liver function tests performed thereafter until the abnormalities return to normal. If increases in AST or ALT concentrations of 3 times the upper limit of normal or higher persist, the dosage of rosuvastatin should be reduced or the drug discontinued. Jaundice has been reported rarely with rosuvastatin therapy.
Musculoskeletal Effects: Myopathy (manifested as muscle pain, tenderness, or weakness and increases in serum creatine kinase (CK) concentration exceeding 10 times the upper limit of normal) has been reported occasionally (up to 0.1%) with rosuvastatin therapy. Rhabdomyolysis (characterized by muscle pain or weakness with marked increases (exceeding 10 times the upper limit of normal) in serum CK concentrations and increases in serum creatinine concentrations (usually accompanied by brown urine and urinary myoglobinuria)) with or without acute renal failure secondary to myoglobinuria has been reported rarely with statin therapy, including with rosuvastatin. Rhabdomyolysis occurs more frequently in patients receiving rosuvastatin 40 mg daily compared with lower dosages. However, it does not appear that the risk of rhabdomyolysis is greater with rosuvastatin than with other statins. In clinical studies, the incidence of myopathy and rhabdomyolysis increased in patients receiving rosuvastatin dosages exceeding the recommended dosage range of 5-40 mg daily.
Risk of myopathy may be increased in patients with predisposing factors for myopathy (e.g., advanced age (65 years or older, particularly women), hypothyroidism), patients receiving rosuvastatin dosages exceeding the recommended dosage range of 5-40 mg daily, and patients at risk of increased exposure to rosuvastatin (e.g., Asian patients, patients with renal impairment). Risk also may be increased by concomitant use of certain drugs, including cyclosporine, niacin, fibric-acid derivatives, macrolide antibiotics (e.g. erythromycin), certain azole antifungals, and alcohol. Use of rosuvastatin with fibric-acid derivatives or niacin should be carefully weighed against the potential risks of this combination; combination therapy with gemfibrozil generally should be avoided.
Discontinue rosuvastatin if serum CK concentrations become markedly elevated (more than 5 times upper limit of normal) or if myopathy is diagnosed or suspected. Temporarily withhold therapy in any patient experiencing an acute, serious condition suggestive of myopathy or predisposing to the development of acute renal failure secondary to rhabdomyolysis (e.g., sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).
General Precautions: Prior to institution of antilipemic therapy, vigorously attempt to control serum cholesterol by appropriate dietary regimens, weight reduction, exercise, and treatment of any underlying disorder that might be the cause of lipid abnormality.
Asian Populations: Pharmacokinetic studies, including a large study conducted in the US, show an approximate twofold elevation in median exposure to rosuvastatin (peak plasma concentration and AUC) in Asian patients (of Filipino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian ancestry) compared with Caucasian patients. This increase should be considered when deciding upon rosuvastatin dosage in Asian patients.
Renal Effects: Transient dipstick-positive proteinuria and microscopic hematuria (not associated with worsening renal function) have been reported in patients receiving rosuvastatin. These findings occurred predominantly in patients receiving higher than recommended dosages (e.g., 80 mg), but were more frequent in patients receiving rosuvastatin 40 mg compared with lower doses of rosuvastatin or comparator statins in clinical trials. Although the clinical importance of this finding is not known, dosage reduction should be considered for patients receiving 40 mg of rosuvastatin daily who have unexplained persistent proteinuria during routine urinalysis testing.
Endocrine Effects: Although clinical studies have shown that rosuvastatin alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, statins interfere with cholesterol synthesis and theoretically may blunt adrenal or gonadal steroid hormone production. Caution should be exercised if any statin, including rosuvastatin, or other agent used to lower cholesterol levels is used concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones (e.g., ketoconazole, spironolactone, cimetidine).
Use in Pregnancy: Fetal/Neonatal Morbidity and Mortality: Suppression of cholesterol biosynthesis could cause fetal harm. Administer to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the patient becomes pregnant while taking the drug, discontinue therapy and apprise the patient of the potential hazard to the fetus.
Use In Pregnancy & Lactation
Pregnancy: Category X.
Cholesterol biosynthesis may be important in fetal development. Contraindicated in pregnancy. Administer to women of childbearing potential only when conception is highly unlikely and patients have been informed of potential hazards.
If the patient becomes pregnant while taking the drug, discontinue therapy and apprise the patient of the potential hazard to the fetus.
Lactation: Excretion in breast milk is unknown/contraindicated.
Adverse Reactions
The statins have been associated with myalgia, myopathy, myositis, and rhabdomyolysis (see Musculoskeletal Effects under Precautions). Statins can alter liver function tests, and rarely cause hepatitis and jaundice; pancreatitis and hepatic failure have been reported very rarely. Other side­-effects include gastro-intestinal disturbances, sleep disturbance, headache, dizziness, depression, paraesthesia, asthenia, peripheral neuropathy, amnesia, fatigue, sexual dysfunction, thrombocytopenia, arthralgia, visual disturbance, alopecia, and hypersensitivity reactions (including rash, pruritus, urticaria, and very rarely lupus erythematosus-like reactions). In very rare cases, statins can cause interstitial lung disease; if patients develop symptoms such as dyspnea, cough, and weight loss, they should seek medical attention. Statins can cause hyperglycemia and may be associated with the development of diabetes mellitus, particularly in those already at risk of the condition. Proteinuria and very rarely hematuria have been reported.
Drug Interactions
Antacids: Potential pharmacokinetic interaction (decreased plasma rosuvasta­tin concentrations with concomitant aluminum-magnesium hydroxide antacid). Administer antacids 2 hours after rosuvastatin.
Bile Acid Sequestrants: Potential pharmacodynamic interaction (enhanced effect on total and LDL-cholesterol) with concomitant bile acid sequestrant.
Cyclosporine: Potential pharmacokinetic interaction (clinically important increases in peak plasma rosuvastatin concentration and AUC with concomitant cyclosporine); limit dosage of rosuvastatin to 5 mg daily with such concomitant therapy.
Digoxin: Pharmacokinetic interaction unlikely (no change in plasma digoxin concentrations with concomitant rosuvastatin).
Drugs Affecting Hepatic Microsomal Enzymes:Pharmacokinetic interaction unlikely (rosuvastatin clearance not dependent on metabolism by cytochrome P-450 isoenzyme 3A4). Interactions (e.g., increases or decreases in AUC of rosuvastatin) between rosuvastatin and ketoconazole, erythromycin, itraconazole, or fluconazole not deemed clinically important.
Fenofibrate: Pharmacokinetic interaction unlikely (no changes in rosuvastatin or fenofibrate plasma concentrations with concomitant administration). (See Musculoskeletal Effects under Precautions).
Gemfibrozil: Increased risk of adverse musculoskeletal effects (e.g., increased CK, myoglobinuria, rhabdomyolysis) with concomitant use. Avoid concomitant use unless potential benefit outweighs risk.
Oral Contraceptives: Potential pharmacokinetic interaction (increased plasma concentrations of ethinyl estradiol and norgestrel) with concomitant rosuvastatin.
Warfarin
: Potential pharmacodynamic interaction (clinically important increase in international normalized ratio (INR)) when rosuvastatin (40 mg) given concomitantly with warfarin (25 mg); plasma warfarin concentrations unchanged. Determine INR prior to initiating rosuvastatin and following any change in dosage and then frequently enough thereafter until stable INR is documented, then at usually recommended intervals.
Antivirals: Possible increased risk of myopathy when rosuvastatin given with atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, ritonavir and saquinavir.
Storage
Store below 30°C.
ATC Classification
C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.
Presentation/Packing
FC tab 10 mg (pink, round shape with inscription 10 on one side, ATC in triangle on other side) x 2 x 14's. 20 mg (pink, round shape with inscription 20 on one side, ATC in triangle on other side) x 2 x 14's.
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