Stravas

Round, peach to orange film-coated tablets. Upon removal of coating, shows white to off-white tablet.
Each Film-Coated Tablet contains: Rosuvastatin Calcium (equivalent to Rosuvastatin 10 mg).
Excipients q.s.

Pharmacology: Pharmacodynamics: Rosuvastatin is a selective and competitive reductase inhibitor of HMG-CoA. HMG-CoA reductase is the rate-limiting enzyme in the conversion of 3-hydroxy-3-methylglutaryl-CoA to methylvalerate, a precursor of cholesterol. The results of animal and cell culture experiments showed that rosuvastatin was selectively taken up by the liver, which is a target organ for lowering cholesterol. In vivo and in vitro studies have shown that rosuvastatin increases the number of LDL receptors on the cell surface, thereby enhancing LDL uptake and catabolism, and inhibits liver VLDL synthesis, thereby reducing the total number of VLDL and LDL particles. In patients with homozygous and heterozygous familial hypercholesterolemia, non-familial hypercholesterolemia, and mixed dyslipidemia, rosuvastatin can reduce total cholesterol, LDL-C, ApoB, and non-HDL-C levels. Rosuvastatin also decreased TG and increased HDL-C levels. For patients with simple hypertriglyceridemia, rosuvastatin can reduce the levels of total cholesterol, LDL-C, VLDLC, ApoB, non-HDL-C, TG, and increase the level of HDL-C. The effect of rosuvastatin on cardiovascular incidence and mortality has not been determined.
Pharmacokinetics: Absorption: Peak plasma concentrations of Rosuvastatin were reached 5 hours following oral dosing. The absolute bioavailability of Rosuvastatin is approximately 20%.
Distribution: Rosuvastatin is ingested in large amounts by liver, which is a major organ for cholesterol synthesis and LDL-C clearance. Mean volume of distribution at steady-state of Rosuvastatin is approximately 134 liters. Rosuvastatin is approximately 90% bound to plasma proteins.
Metabolism: Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite. In vitro studies on the metabolism of human hepatocytes showed that rosuvastatin is a weak substrate for cytochrome P450 metabolism. The main isoenzyme involved in metabolism was CYP 2C9, and 2C19, 3A4 and 2D6 were less involved in metabolism. The known metabolites are N-demethylated and lactone metabolites. The N-demethylated metabolite was 50% less active than rosuvastatin, while the lactone metabolite was considered clinically inactive. Overall, greater than 90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by the parent compound.
Elimination: Following oral administration, about 90% of Rosuvastatin and its metabolites are primarily excreted in the feces (including absorbed and unabsorbed active substance), the rest is excreted in the urine. About 5% in the urine is protoforma. The elimination half-life of Rosuvastatin is approximately 19 hours. The clearance period was not prolonged with the increase of dose. The geometric mean of plasma clearance was 50L/h (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, hepatic uptake of rosuvastatin involves the membrane transporter OATP-C. This transporter is important in liver clearance of rosuvastatin.

Rosuvastatin is suitable for primary hyperlipidemia (IIa, including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (IIb) that cannot be properly controlled by diet and non-pharmacological interventions (such as exercise therapy and weight reduction). Rosuvastatin is also indicated in patients with homozygous familial hypercholesterolemia, as an adjuvant to dietary control and other lipid-lowering measures (such as LDL removal therapy), or when these methods are not applicable.

Patients should be given a standard cholesterol-lowering diet prior to the start of treatment and maintained throughout the course of treatment.
Oral administration. The usual starting dose is 5 mg (one tablet), once a day. The choice of the starting dose should take into account the individual's cholesterol level, expected cardiovascular risk, and potential risk of adverse reactions. For patients who require a more aggressive reduction of low-density lipoprotein cholesterol (LDL-C), a starting dose of 10 mg once a day should be considered, which controls lipid levels in most patients. If necessary, the dose can be adjusted to the higher dose level after 4 weeks of treatment. The maximum daily dose is 20 mg. Rosuvastatin can be administered as a single dose at any time of day, with or without food.

There is no specific treatment for overdose of Rosuvastatin. In the event of overdose, symptomatic treatment should be given, with supportive measures as needed. Liver function and CK level should be monitored. Hemodialysis may not be effective.

Rosuvastatin is contraindicated for people who are allergic to Rosuvastatin or any of its component; patients with active liver disease, including patients with unexplained persistent elevation of serum transaminase and any elevation of serum transaminase that exceeds 3 times the upper limit of normal (ULN); patients with severe renal impairment (creatinine clearance <30 ml/min); patients with myopathy; patients who are also using cyclosporine; and women who are pregnant, breastfeeding, or at risk of becoming pregnant without using appropriate contraception.

Renal Effects: Proteinuria (dipstick) was observed in patients treated at high doses, especially 40mg. Proteinuria was mostly derived from renal tubules and in most cases was transient or intermittent. Proteinuria is not considered as a precursor of acute or progressive nephropathy.
Skeletal Muscle Effects: Effects on skeletal muscle have been reported in patients receiving a variety of doses of Rosuvastatin, such as myalgia, myopathy, and rare rhabdomyolysis, especially at doses greater than 20 mg.
Creatine kinase testing: Creatine kinase testing should not be done after strenuous exercise or when there is a plausible cause of an increase in creatine kinase (CK), which could confuse interpretation of the results. If the basal value of creatine kinase was significantly increased (<5×ULN), should be tested within 5-7 days for confirmation. If repeated tests confirm the patient's basal creatine kinase value >5×ULN, treatment should not be initiated.
Liver effects: As with other HMG-CoA reductase inhibitors, Rosuvastatin should be used with caution in heavy alcohol consumption and/or with a history of liver disease. Liver function testing is recommended before and 3 months after initiation of treatment. If the increase of serum transaminase is more than 3 times the upper limit of normal value, Rosuvastatin should be discontinued or the dose should be reduced. In cases of hypercholesterolemia secondary to hypothyroidism or nephrotic syndrome, the primary disease should be treated before starting to treat with Rosuvastatin.
Lactose intolerance: Patients with rare hereditary galactose intolerance, lactase deficiency, or malabsorption of glucose-galactose should not take Rosuvastatin.
Interstitial pulmonary disease: Rare cases of interstitial pulmonary disease have been reported in some statin therapy, especially in those on long-term treatment. Symptoms include difficulty breathing, dry cough without phlegm, and general decline in health (fatigue, weight loss, and fever). Statin therapy should be discontinued in patients with suspected interstitial pulmonary disease.
Diabetes: According to some reports, use of HMG-CoA reductase inhibitors (including Rosuvastatin) and Glycated haemoglobin A1C, HbA1c) was associated with elevated fasting serum glucose levels. Patients at risk (FBG: 5.6 ~ 6.9 mmol/L, BMI >30 kg/m², elevated triglycerides, hypertension) should be monitored clinically and biochemically in accordance with relevant guidelines.

Rosuvastatin is prohibited for pregnant women and lactating women. Women who are at risk of being pregnant should use appropriate contraception. Because cholesterol and other cholesterol biosynthesis products are important for embryonic development, the risk from HMG-CoA reductase inhibition outweighs the benefit of treatment for pregnant women. Animal studies provide limited evidence of reproductive toxicity. If the patient is pregnant during the use of Rosuvastatin, treatment should be discontinued immediately. Rosuvastatin can be secreted into rat breast milk. There is no data on Rosuvastatin secretion into human breast.

Adverse reactions observed with Rosuvastatin are usually mild and temporary. As with other HMG-CoA reductase inhibitors, the incidence of adverse reactions tended to increase with increasing dose.
Renal effects: Proteinuria, hematuria.
Effects on skeletal muscle: Myalgia, myopathy, and rare rhabdomyolysis.
Liver effects: Dose-dependent elevation of transaminase.
The following adverse events have been reported with some statin therapy: Sexual dysfunction, special cases of interstitial pulmonary disease, especially those receiving long-term treatment.
Statins: 1. In the post-marketing monitoring of statins, there were reports of hyperglycemia reaction, abnormal glucose tolerance, elevated glycosylated hemoglobin level, new-onset diabetes, and deterioration of blood glucose control. Some statins also had reports of hypoglycemia reaction.
2. Post-marketing experience: In the post-marketing monitoring of statins abroad, there have been rare reports of cognitive impairment, manifested as memory loss, memory decline, thinking confusion, etc., which are mostly non-serious and reversible reactions, which can be recovered after withdrawal.

Transporter inhibitors: When use together, may result in elevated plasma concentrations of rosuvastatin and an increased risk of myopathy, including rhabdomyolysis.
Cyclosporine: When Rosuvastatin is used in combination with cyclosporine, the AUC of rosuvastatin is 7 times higher than that observed in healthy volunteers. Rosuvastatin is contraindicated in patients receiving concurrent cyclosporine therapy.
Protease inhibitors: Although the mechanism of drug interaction is unclear, concurrent use of protease inhibitors may significantly increase rosuvastatin exposure.
Gemfibrozil and other lipid-lowering products: When used in combination with gemfibrozil, 2-fold increase in Cmax and AUC of rosuvastatin. The combination of fenofibrate and other lipid-lowering doses (≥1 g/day) with HMG-CoA reductase inhibitors increases the risk of myopathy, possibly because they can cause myopathy when given alone.
Ezetimibe: The combination of rosuvastatin and ezetimibe 10 mg resulted in a 1.2-fold increase in rosuvastatin AUC in subjects with hypercholesterolemia.
Antacid drugs: When administered together with an antacid suspension containing magnesium hydroxide, the plasma concentration of rosuvastatin is reduced by approximately 50%. This effect can be alleviated if the antacid is administered 2 hours after administration.
Erythromycin: When combined with erythromycin, the AUC and Cmax of rosuvastatin decreased by 20% and 30%, respectively. This interaction may be due to the increased gastrointestinal motility induced by erythromycin.
Colchicine: Myopathy including rhabdomyolysis has been reported when HMG-CoA reductase inhibitors, including rosuvastatin, are combined with colchicine. Therefore, caution should be taken when rosuvastatin is combined with colchicine.

Store at temperatures not exceeding 30°C.

Dyslipidaemic Agents

C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.

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