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Patients should be placed on a standard cholesterol-lowering diet (at least equivalent to the Adult Treatment Panel III (ATP III TLC diet) before receiving Otagil (Rosuvastatin calcium), and should continue on this diet during treatment with Otagil. If appropriate, a program of weight control and physical exercise should be implemented.
Prior to initiating therapy with Otagil, secondary causes for elevations in plasma lipid levels should be excluded. A lipid profile should also be performed. After initiation or upon titration of Otagil, lipid levels should be analyzed within 2-4 weeks and the dosage adjusted accordingly.
The usual recommended starting dose of Otagil is 10 mg once daily. However, initiation of therapy with 5 mg once daily should be considered for special patient populations or patients requiring less aggressive LDL-C reductions. The choice of starting dose should take into account the individual patients' cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions. Otagil may be taken in the morning or evening, with or without food. The majority of patients are controlled at the 10 mg dose. However, if necessary, dose adjustments to the next dose level can be made after 4 week intervals. The maximum response is usually achieved within 2-4 weeks and is maintained during chronic therapy. Increasing the dose to 40 mg should be reserved for patients with severe hypercholesterolemia at high cardiovascular risk (in particular those with familial hypercholesterolemia), who do not achieve their treatment goal on 20 mg and should only be initiated under specialist supervision (see Precautions). The physician who elects to use Otagil at a dose higher than 20 mg should periodically re-evaluate the long term risk/benefit of Otagil for the individual patient. Otagil should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis (see Precautions).
The dosage of Otagil should be individualized according to baseline LDL-C, total-C/HDL-C ratio and/or TG levels, the recommended target lipid values (see Recommendations for the Management and Treatment of Dyslipidemia [Canada] summarized as follows in Table 1) and/or the Third Report of the U.S. National Cholesterol Education Program [NCEP Adult Treatment Panel III]) and the patient response.
The majority (80%) of patients treated with Rosuvastatin 10 mg achieved their NCEP ATP III treatment target for LDL-C levels; fewer subjects (68%) achieved target on the 5 mg dose. The difference between Rosuvastatin 5 mg and 10 mg was greatest for high risk subjects (40% versus 61%, respectively), i.e. for subjects who have a lower LDL-C target.
Lipid levels should be monitored periodically and, if necessary, the dose of Otagil adjusted based on target lipid levels recommended by guidelines. (See Table 1.)
Click on icon to see table/diagram/imageThe following reductions in total cholesterol, LDL-C, TG, Total-C/HDL and increases in HDL-C have been observed in a dose-response study, and may serve as a guide to treatment of patients with mild to moderate hypercholesterolemia: (See Table 2.)
Click on icon to see table/diagram/imageDosage in patients with renal insufficiency: The usual dose range applies in patients with mild to moderate renal impairment.
For patients with severe renal impairment (CLcr <30 mL/min/1.73 m2) not on hemodialysis, dosing of Otagil should be started at 5 mg once daily and not exceed 10 mg once daily (see Pharmacology: Pharmacokinetics under Actions).
Dosage in patients with hepatic insufficiency: There was no increase in systemic exposure to Rosuvastatin in subjects with Child-Pugh scores of 7 or below. However, increased systemic exposure has been observed in subjects with Child-Pugh scores of 8 and 9. In these patients an assessment of renal function should be considered. There is no experience in subjects with Child-Pugh scores above 9. Otagil is contraindicated in patients with active liver disease.
Use in the elderly: Of the 10,275 patients in clinical studies with Rosuvastatin, 3,159 (31%) were 65 years and older, and 698 (6.8%) were 75 years and older. The overall frequency of adverse events and types of adverse events were similar in patients above and below 65 years of age. The efficacy of Rosuvastatin in the geriatric population (≥65 years of age) was comparable to the efficacy observed in the non-elderly.
Pediatric patients (10 to 17 years of age): In pediatric patients (10 to 17 years of age) with heterozygous familial hypercholesterolemia the usual dose range of Otagil is 5-20 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy (see Indications/Uses). Adjustments should be made at intervals of 4 weeks or more.
Use in children below 10 years: The safety and effectiveness in children have not been established. In children and adolescents with homozygous familial hypercholesterolemia experience is limited to eight patients (aged 8 years and above).
Dosage on Asian patients: Initiation of Otagil therapy with 5 mg once daily should be considered for Asian patients. The potential for increased systemic exposures relative to Caucasians is relevant when considering escalation of dose in cases where hypercholesterolemia is not adequately controlled at doses of 5, 10 or 20 mg once daily (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Genetic polymorphisms: Specific types of genetic polymorphisms are known that can lead to increased Rosuvastatin exposure (see Pharmacology: Pharmacokinetics under Actions). For patients who are known to have such specific types of polymorphisms, a lower daily dose of Otagil is recommended.
Dosage in patients with pre-disposing factors to myopathy: The recommended start dose is 5 mg in patients with predisposing factors to myopathy (see Precautions).
Concomitant therapy: Rosuvastatin is a substrate of various transporter proteins (e.g. OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when Otagil is administered concomitantly with certain medicinal products that may increase the plasma concentration of Rosuvastatin due to interactions with these transporter proteins (e.g. Ciclosporin and certain protease inhibitors including combinations of Ritonavir with Atazanavir, Lopinavir, and/or Tipranavir; (see Precautions and Interactions). Whenever possible, alternative medications should be considered, and, if necessary, consider temporarily discontinuing Otagil therapy.
In situations where co-administration of these medicinal products with Otagil is unavoidable, the benefit and the risk of concurrent treatment and Otagil dosing adjustments should be carefully considered (see Interactions). If concomitant use of Otagil with Ciclosporin cannot be avoided, the dose of Otagil should not exceed 5 mg once daily (see Precautions and Interactions).
