Rosuva EZ Tablet

Rosuva EZ Tablet is used for: Hyperlipidemia, hypercholesterolemia

Oral Adult As an adjunct to diet in adults with primary non-familial hyperlipidemia to reduce low-density lipoprotein cholesterol (LDLC), Alone or as an adjunct to other LDL-C lowering therapies in adults with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C The recommended dosage range of Rosuvastatin + Ezetimibe is one tablet (containing 5 mg to 40 mg of rosuvastatin and 10 mg of ezetimibe) Orally once daily. Dosage range is 5 mg/10 mg to 40 mg/10 mg once daily. Initiate at 5 mg/10 mg once daily. Consider the risk/benefit when treating Asian patients not adequately controlled at doses up to 20 mg/10 mg once daily Assess LDL-C as early as 2 weeks after initiating Rosuvastatin + Ezetimibe, and adjust dosage as necessary.

Renal Impairment In patients with severe renal impairment (CLcr less than 30 mL/min/1.73 m2) not on hemodialysis, the recommended starting dosage is 5 mg/10 mg once daily and should not exceed 10 mg/10 mg once daily There are no dosage adjustment recommendations for patients with mild and moderate renal impairment.

Swallow tablets whole at any time of the day, with or without food. Do not crush, dissolve, or chew tablets.

Acute liver failure or decompensated cirrhosis. Hypersensitivity to rosuvastatin, ezetimibe, or any excipients in Rosuvastatin + Ezetimibe

Myopathy and Rhabdomyolysis: Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher Rosuvastatin + Ezetimibe dosage. Asian patients may be at higher risk for myopathy. Discontinue Rosuvastatin + Ezetimibe if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue Rosuvastatin + Ezetimibe in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing Rosuvastatin + Ezetimibe dosage. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported with statin use. Discontinue Rosuvastatin + Ezetimibe if IMNM is suspected. Hepatic Dysfunction: Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzyme before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue Rosuvastatin + Ezetimibe.

Pregnancy Risk Summary Discontinue Rosuvastatin + Ezetimibe when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Rosuvastatin + Ezetimibe decreases the synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, Rosuvastatin + Ezetimibe may cause fetal harm when administered to pregnant patients based on the mechanism of action. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with rosuvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage. In animal reproduction studies, oral administration of rosuvastatin to pregnant rats and rabbits during organogenesis at doses equivalent to the maximum recommended human dose (MRHD) of 40 mg/day resulted in no adverse developmental effects. There are insufficient data on ezetimibe use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of ezetimibe to pregnant rats and rabbits during organogenesis at doses 10 and 150 times, respectively, the MRHD resulted in no adverse developmental effects. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Human Data A Medicaid cohort linkage study of 1,152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Animal Data Rosuvastatin Rosuvastatin administration did not indicate a teratogenic effect in rats at <25 mg/kg/day or in rabbits <3 mg/kg/day (doses equivalent to the MRHD of 40 mg/day based on AUC and body surface area, respectively). In female rats given 5, 15 and 50 mg/kg/day before mating and continuing through to gestation day 7 resulted in decreased fetal body weight (female pups) and delayed ossification at 50 mg/kg/day (10 times the human exposure at the MRHD dose of 40 mg/day based on AUC). In pregnant rats given 2, 10 and 50 mg/kg/day of rosuvastatin from gestation day 7 through lactation day 21 (weaning), decreased pup survival occurred at 50 mg/kg/day (dose equivalent to 12 times the MRHD of 40 mg/day based body surface area). In pregnant rabbits given 0.3, 1, and 3 mg/kg/day of rosuvastatin from gestation day 6 to day 18, decreased fetal viability and maternal mortality was observed at 3 mg/kg/day (dose equivalent to the MRHD of 40 mg/day based on body surface area). Rosuvastatin crosses the placenta in rats and rabbits and is found in fetal tissue and amniotic fluid at 3% and 20%, respectively, of the maternal plasma concentration following a single 25 mg/kg oral gavage dose on gestation day 16 in rats. A higher fetal tissue distribution (25% maternal plasma concentration) was observed in rabbits after a single oral gavage dose of 1 mg/kg on gestation day 18. Ezetimibe In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats (gestation days 6-15) and rabbits (gestation days 7-19), there was no evidence of maternal toxicity or embryolethality at any dose tested (250, 500, 1,000 mg/kg/day) at exposures equivalent to 10 and 150 times the clinical exposure, based on AUC, in rats and rabbits. In rats, increased incidences of common fetal skeletal findings (extra pair of thoracic ribs, unossified cervical vertebral centra, shortened ribs) were observed at 1000 mg/kg/day (~10 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). In rabbits treated with ezetimibe, an increased incidence of extra thoracic ribs was observed at 1000 mg/kg/day (150 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). The animal-to-human exposure multiple for total ezetimibe at the no observed effect level was 6 times for rat and 134 times for rabbit. Fetal exposure to ezetimibe (conjugated and unconjugated) was confirmed in subsequent placental transfer studies conducted using a maternal dose of 1000 mg/kg/day. The fetal maternal plasma exposure ratio (total ezetimibe) was 1.5 for rats on gestation day 20 and 0.03 for rabbits on gestation day 22. The effect of ezetimibe on prenatal and postnatal development and maternal function was evaluated in pregnant rats at doses of 100, 300 or 1,000 mg/kg/day (gestation day 6 through lactation day 21). No maternal toxicity or adverse developmental outcomes were observed up to and including the highest dose tested (17 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). Multiple dose studies of ezetimibe given in combination with statins in rats and rabbits during organogenesis resulted in higher ezetimibe and statin exposures. Reproductive findings occurred at lower doses in combination therapy compared to monotherapy. Lactation Risk Summary Limited data from case reports in published literature indicate that rosuvastatin is present in human milk. There is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Statins, including Rosuvastatin + Ezetimibe, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. There is no information about the presence of ezetimibe in human milk. Ezetimibe is present in rat milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. There is no information about the effects of ezetimibe on the breastfed infant or the effects of ezetimibe on milk production. Because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with Rosuvastatin + Ezetimibe. Ezetimibe was present in the milk of lactating rats. The pup to maternal plasma ratio for total ezetimibe was 0.5 on lactation day 12.

Gemfibrozil or Cyclosporin: Avoid concomitant use with Rosuvastatin + Ezetimibe. Fenofibrates, Niacin, Colchine: Consider the risks and benefits of concomitant use with Rosuvastatin + Ezetimibe. Bile Acid Sequestrants: Cholestyramine combination decreases exposure of Rosuvastatin + Ezetimibe. Aluminum and Magnesium Hydroxide Combination Antacids: Administer Rosuvastatin + Ezetimibe at least 2 hours before the antacid. Warfarin: Obtain INR before Rosuvastatin + Ezetimibe initiation. Monitor INR frequently until stable upon initiation, dose titration, or discontinuation

Side effects of Rosuvastatin + Ezetimibe : Most common adverse reactions for: Rosuvastatin (incidence >2% and greater than placebo) are headache, nausea, myalgia, asthenia, and constipation. Ezetimibe (incidence >2% and greater than placebo) are upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremity, and fatigue. Ezetimibe co-administered with a statin (incidence >2% and greater than statin alone) are nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, diarrhea, back pain, influenza, and pain in the extremity.

Rosuvastatin Rosuvastatin is an inhibitor of HMG CoA-reductase, the rate-limiting enzyme that converts 3-hydroxy3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. Ezetimibe Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe is the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols. Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in the clearance of cholesterol from the blood.

Rosuva EZ 20 mg+10 mg Tablet manufactured by Square Pharmaceuticals PLC.. Its generic name is Rosuvastatin + Ezetimibe. Rosuva EZ is availble in Bangladesh. Farmaco BD drug index information on Rosuva EZ Tablet is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.