Indications/Uses
Reduce elevated total-C, LDL-C, non-HDL, Apo B and triglycerides levels and to increase HDL-C in patients with homozygous familial hypercholesterolemia and mixed dyslipidemia as adjunct to diet and other non-pharmacological or lipid lowering treatments (eg, LDL apheresis) or if such treatments are unavailable or inadequate. As adjunct to diet for the treatment of patients with elevated serum triglyceride levels (hypertriglyceridemia/Fredrickson Type IV).
Dosage/Direction for Use
The patient should be placed on a standard cholesterol-lowering diet before receiving rosuvastatin and should continue on this diet during treatment with rosuvastatin. Rosuvastatin can be administered as a single dose at any time of the day, with or without food.
Homozygous Familial Hypercholesterolemia: Recommended Starting Dose: 20 mg once daily in patients with homozygous familial hypercholesterolemia. Maximum Recommended Dose: 40 mg daily. Rovista should be used in these patients as an adjunct to other lipid-lowering treatments.
The following guidelines may be used to establish treatments goals: See table.
Mixed Dyslipidemia (Fredrickson Type IIa and IIb): Dose Range: 5-40 mg once daily. Therapy with rosuvastatin should be individualized according to goal of therapy and response. Usual Recommended Dose: 10 mg once daily. Initiation of therapy with 5 mg once daily may be considered for patients requiring less aggressive LDL-C reductions or who have predisposing factors for myopathy.
Patients with Marked Hypercholesterolemia (LDL-C >190 mg/dL) and Aggressive Lipid Targets: Starting Dose: 20 mg. After initiation and/or upon titration of Rovista, lipid levels should be analyzed within 2-4 weeks and dosage adjusted accordingly. The 40-mg dose of Rovista is reserved only for those patients who have not achieved its LDL-C goal utilizing the 20-mg dose of Rovista once daily.
Elevated Serum Triglyceride Levels (Hypertriglyceridemia/Frederickson Type IV): Dose Range: 5-40 mg once daily. Usual Starting Dose: 10 mg/day with adjustments based on lipid levels, monitored once daily 2-4 weeks until desired level is achieved.
Administration
May be taken with or without food.
Contraindications
Patients with allergy to any components of Rovista. Active liver disease including unexplained persistent elevation of serum transaminases and any serum transaminases elevation exceeding 3 times the upper limit of normal (ULN); severe renal impairment (CrCl <30 mL/min); myopathy; receiving concomitant cyclosporine.
Use in Pregnancy and Lactation: Contraindicated during pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.
Special Precautions
Before instituting therapy with rosuvastatin, an attempt should be made to control hypercholesterolemia, with appropriate diet, exercise and weight reduction in obese patients and to treat other underlying medical problems. When initiating statin therapy or switching from another statin therapy, the appropriate rosuvastatin starting dose should be first be utilized and only then titrated according to the patient's individualized goal of therapy. HMG-CoA reductase inhibitors eg, some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. It is recommended that liver function tests be performed before and at 12 weeks following both the initiation of therapy and any elevation of dose and periodically thereafter.
Use in Children: Safety and efficacy have not been established in children.
Use In Pregnancy & Lactation
Contraindicated during pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.
Adverse Reactions
Rosuvastatin is generally well-tolerated. Adverse reactions have usually been mild and transient. Common: Headache, dizziness, constipation, nausea, abdominal pain, myalgia, asthenia.
Uncommon: Pruritus, rash and urticaria.
Rare: Hypersensitivity reactions including angioedema, myopathy, rhabdomyolysis, arthralgia, increased hepatic transaminases.
Very Rare: Jaundice, hepatitis, polyneuropathy.
Laboratory Abnormalities: Proteinuria has been observed in patients treated with rosuvastatin. This finding was more frequent in patients taking rosuvastatin 40 mg, when compared to lower doses of the drug. Other abnormal laboratory values reported were elevated creatinine phosphokinase, dose related increase in transaminases, hyperglycemia, glutamyl transpeptidase, alkaline phosphate, bilirubin and thyroid function abnormalities.
Drug Interactions
Warfarin: Co-administration of rosuvastatin to patients on stable warfarin therapy resulted in clinically significant rises in INR (>4, baseline 2-3).
Coumarin: 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.
Antacid: The antacid should be taken at least 2 hrs after rosuvastatin administration.
Storage
Store at temperatures not exceeding 30°C. Protect from sunlight and moisture.
Action
Pharmacology: Mechanism of Action: Rosuvastatin is a selective inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering in in vivo and in vitro studies, rosuvastatin produces its lipid-modifying effects in 2 ways. First, it increases the number of hepatic LDL receptors on the cell surface to enhance uptake and catabolism of low-density lipoprotein (LDL). Second, rosuvastatin inhibits hepatic synthesis of very low-density lipoprotein (VLDL), which reduces the total number of VLDL and LDL particles.
Pharmacokinetics: Absorption: Maximum plasma concentration is achieved approximately in 5 hrs after oral administration. The absolute bioavailability is approximately 20%. Both peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in approximately proportion to rosuvastatin dose.
Administration of rosuvastatin with food decreased the rate of drug absorption by 20% as assessed by Cmax but there was no effect on the extent of absorption as assessed by AUC.
Distribution: Rosuvastatin is taken up extensively by the liver which is the primary site of cholesterol synthesis and LDL-C clearance. Mean volume of distribution at steady state of rosuvastatin is approximately 134 L. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations.
Metabolism: Rosuvastatin is not extensively metabolized, (approximately 10%). The major metabolites is N-desmethyl (50% less active than parent), which is formed principally by cytochrome P-450 2C9, and lactone metabolite (clinically inactive). Rosuvastatin accounts for >90% of the circulating HMG-CoA reductase inhibitor activity.
Excretion: Following an oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%) and approximately 5% is excreted unchanged in the urine. The elimination t½ of rosuvastatin is approximately 19 hrs. The elimination t½ does not increase at higher doses.
Special Populations: Renal Insufficiency: Subjects with varying degrees of renal impairment, mild to moderate renal disease had little influence on plasma concentrations of rosuvastatin. However, subjects with severe impairment (CrCl <30 mL/min) had a 3-fold increase in plasma concentration compared to healthy volunteers. Steady-state plasma concentration of rosuvastatin in patients on chronic hemodialysis were approximately 50% greater compared to healthy volunteer subjects with normal renal function.
Hepatic Insufficiency: In patients with chronic alcohol liver disease, plasma concentrations of rosuvastatin were modesty increased. In patients with Child-Pugh A disease, Cmax and AUC were increased by 60% and 5% respectively, as compared with patients with normal liver function. In patients with Child-Pugh B disease, Cmax and AUC were increased 100% and 21%, respectively, compared with patients with normal liver function.
Drug-Drug Relationship: Cyclosporine: Co-administration of cyclosporine with rosuvastatin resulted 11- and 7-fold increase in Cmax and AUC of rosuvastatin respectively, compared with healthy subjects.
Gemfibrozil: Co-administration of a single rosuvastatin dose to healthy volunteers on gemfibrozil (600 mg twice daily) resulted in a 2.2- and 1.9-fold increase in mean Cmax and mean AUC of rosuvastatin, respectively.
Antacid: Co-administration of an antacid (aluminum and magnesium hydroxide combination) with rosuvastatin (40 mg) resulted in a decrease in plasma concentrations of rosuvastatin by approximately 50%.
Oral Contraceptives: Co-administration of oral contraceptives (ethinyl estradiol and norgestrel) with rosuvastatin resulted in an increase in plasma concentrations of ethinyl estradiol and norgestrel by 28% and 34%, respectively.
Erythromycin: Concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease in AUC and a 30% decreased in Cmax of rosuvastatin.
MedsGo Class
Dyslipidaemic Agents
Features
- Rosuvastatin