Zyrova Special Precautions

10 mg & 20 mg: HMG-CoA reductase inhibitors, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. It is recommended that liver function tests be performed prior to and 12 weeks following both the initiation of therapy and any elevation of dose, and periodically thereafter. Should an increase in ALT or AST >3 times the upper limit of normal persist, reduction of dose or withdrawal of rosuvastatin is recommended. Rosuvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease.
Rare case of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with rosuvastatin and with other drug in this class. Myopathy defined as muscle aches or weakness in conjunction with an increase in creatinine phosphokinase (CPK) values, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness. Rosuvastatin therapy should be discontinued if markedly elevated CPK levels >5 times the upper limit of normal occur or myopathy is diagnosed or suspected. The risk of myopathy during treatment with rosuvastatin is increased with concurrent administration of other lipid-lowering therapies or cyclosporine. The benefit of further alterations in lipid levels by the combined use of rosuvastatin with fibrates or niacin should be carefully weighed against the potential risks of this combination. Combination therapy with rosuvastatin and gemfibrozil should generally be avoided. Rosuvastatin therapy should be temporarily withheld 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). Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy eg, renal impairment, advanced age and hypothyroidism.
Before instituting therapy with rosuvastatin, an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, weight reduction in obese patients and treatment of underlying medical problems.
40 mg: Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy (e.g. age > 65 years, inadequately treated hypothyroidism, renal impairment).
The risk of myopathy during treatment with Rosuvastatin may be increased with concurrent administration of some other lipid-lowering therapies (fibrates or niacin), gemfibrozil, cyclosporine, lopinavir/ritonavir, or atazanavir/ritonavir. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, co-administered with colchicine, and caution should be exercised when prescribing Rosuvastatin with colchicine.
Rosuvastatin therapy should be discontinued if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected. Rosuvastatin therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures).
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with stain use. IMNM is characterized by : proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation, improvement with immunosuppressive agents.
All patients should be advised to promptly report to their physician unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing Rosuvastatin.
Liver Enzyme Abnormalities: It is recommended that liver enzyme tests be performed before the initiation of Rosuvastatin, and if signs or symptoms of liver injury occur.
Increases in serum transaminases [AST (SGOT) or ALT (SGPT)] have been reported with HMG-CoA reductase inhibitors, including Rosuvastatin. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy. There were two cases of jaundice, for which a relationship to Rosuvastatin therapy could not be determined, which resolved after discontinuation of therapy. There were no cases of liver failure or irreversible liver disease in these trials.
There have been postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including rosuvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with Rosuvastatin, promptly interrupt therapy. If an alternate etiology is not found, do not restart Rosuvastatin.
Rosuvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease. Active liver disease, which may include unexplained persistent transaminase elevations, is a contraindication to the use of Rosuvastatin.
Concomitant Coumarin Anticoagulants: Caution should be exercised when anticoagulants are given in conjunction with Rosuvastatin because of its potentiation of the effect of coumarin-type anticoagulants in prolonging the prothrombin time/INR. In patients taking coumarin anticoagulants and Rosuvastatin concomitantly, INR should be determined before starting Rosuvastatin and frequently enough during early therapy to ensure that no significant alteration of INR occurs.
Proteinuria and Hematuria: In the Rosuvastatin clinical trial program, dipstick-positive proteinuria and microscopic hematuria were observed among Rosuvastatin treated patients. These findings were more frequent in patients taking Rosuvastatin 40 mg, when compared to lower doses of Rosuvastatin or comparator HMG-CoA reductase inhibitors, though it was generally transient and was not associated with worsening renal function. Although the clinical significance of this finding is unknown, a dose reduction should be considered for patients on Rosuvastatin therapy with unexplained persistent proteinuria and/or hematuria during routine urinalysis testing.
Endocrine Effects: Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including Rosuvastatin. Based on clinical trial data with Rosuvastatin, in some instances these increases may exceed the threshold for the diagnosis of diabetes mellitus. Although clinical studies have shown that Rosuvastatin alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, caution should be exercised if Rosuvastatin is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine.
Asian Patients: Pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in Asian subjects when compared with Caucasian controls. Rosuvastatin dosage should be adjusted in Asian Patients.
Renal Impairment: Rosuvastatin exposure is not influenced by mild to moderate renal impairment (CLcr ≥30 mL/min/1.73 m²); however, exposure to rosuvastatin is increased to a clinically significant extent in patients with severe renal impairment who are not receiving hemodialysis. Rosuvastatin dosing should be adjusted in patients with severe renal impairment (CLcr ≥30mL/min/1.73 m²) not requiring hemodialysis.
Hepatic Impairment: Rosuvastatin is contraindicated in patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels. Chronic alcohol liver disease is known to increase rosuvastatin exposure; Rosuvastatin should be used with caution in these patients.
Use in Children: 5 mg: The safety and effectiveness of Rosuvastatin in pediatric patients have been established.
10 mg & 20 mg: The safety and efficacy of Zyrova has not been established in children.
40 mg: The safety and effectiveness of Rosuvastatin in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia were evaluated in a controlled clinical trial of 12 weeks duration followed by 40 weeks of open-label exposure. Patients treated with 5 mg, 10 mg, and 20 mg daily Rosuvastatin had an adverse experience profile generally similar to that of patients treated with placebo. Although not all adverse reactions identified in the adult population have been observed in clinical trials of children and adolescent patients, the same warnings and precautions for adults should be considered for children and adolescents. There was no detectable effect of Rosuvastatin on growth, weight, BMI (body mass index), or sexual maturation in pediatric patients (10 to 17 years of age). Adolescent females should be counseled on appropriate contraceptive methods while on Rosuvastatin therapy. Rosuvastatin has not been studied in controlled clinical trials involving pre-pubertal patients or patients younger than 10 years of age. Doses of Rosuvastatin greater than 20 mg have not been studied in the pediatric population.
Use in the Elderly: 5 mg: Elderly patients are higher risk of myopathy and Rosuvastatin should be prescribed with caution in the elderly.
40 mg: Of the 10,275 patients in clinical studies with Rosuvastatin, 3159 (31%) were 65 years and older, and 698 (.8%) were 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients are at higher risk of myopathy and Rosuvastatin should be prescribed with caution in the elderly.