COMPOSITIONS :
Rosuvastatin Calcium Film coated tablet 10 mg, each film coated tablet contains : Rosuvastatin calcium equivalent to Rosuvastatin 10 mg.
DESCRIPTIONS :
Rosuvastatin Calcium with active ingredient Rosuvastatin calcium (equivalent with Rosuvastatin) is available in 10 mg and 20 mg film coated tablet.
INDICATIONS :
Rosuvastatin Calcium is indicated for :
- Patients with primary hypercholesterolaemia (type IIa, including heterozygous familial hypercholesterolaemia) or mixed dyslipidemia (type IIb) as an adjunct to diet when response to diet and exercise is inadequate.
- Reduces elevated LDL-cholesterol, total cholesterol, triglycerides and ApoB, and increases HDL-cholesterol.
- Patients with homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid lowering treatments (e.g., LDL apheresis).
DOSAGE AND ADMINISTRATIONS :
Before initiating treatment with Rosuvastatin calcium, the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment. The dose of Rosuvastatin calcium should be individualized according to the goal of therapy and patient response, using the current consensus guidelines.
The recommended starting dose is 5 or 10 mg once daily in both statin naive patients or patients switched from another HMG-CoA reductase inhibitor. 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. A dose adjustment to the next dose level can be made after 4 weeks, if necessary. In light of the increased reporting rate of adverse reactions with the 40 mg dose compared to lower doses, a final titration to the maximum dose of 40 mg should only be considered in patients with severe hypercholesterolaemia at high cardiovascular risk (in particular dose with familial hypercholesterolaemia), who do not achieve their treatment goal on 20 mg, and in whom routine follow-up will be performed. Specialist supervision is recommended when the 40 mg dose is initiated.
Rosuvastatin calcium may be given at any time of day, with or without food.
- Use in children
Safety and efficacy have not been established in children. Pediatric experience is limited to a small number of children (aged 8 years or above) with homozygous familial hypercholesterolaemia. Therefore, Rosuvastatin calcium is not recommended for pediatric use at this time.
- Use in the elderly
A starting dose of 5 mg is recommended in patients > 70 years. No other dose adjustment is necessary in relation to age.
- Patients with renal insufficiency
No dose adjustment is necessary in patients with mild to moderate renal impairment. For patients with severe renal impairment (CLcr < 30 ml/min/1.73 m2) not on haemodialysis, dosing of Rosuvastatin calcium should be started at 5 mg once daily and not to exceeded 10 mg once daily.
- Patients with hepatic impairment
There was no increase in systemic exposure to Rosuvastatin calcium 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 and the dose of Rosuvastatin calcium should not exceeded 20 mg once daily. There is no experience in subjects with Child-Pugh scores above 9.
- Race
Increase plasma concentration of Rosuvastatin calcium has been seen in Asian subjects. Initiation of therapy with 5 mg once daily should be considered for Asian patients. The increased systemic exposure should be taken into consideration when treating Asian patients particularly in those whose hypercholesterolaemia is not adequately controlled a doses up to 20 mg/daily.
- Patients with pre-disposing factors to myopathy
The recommended starting dose is 5 mg.
OVERDOSAGE :
There is no specific treatment in the event of overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Liver function and Creatinine Kinase (CK) levels should be monitored. Haemodialysis is unlikely to be of benefit.
CONTRAINDICATIONS :
- Hypersensitivity to any component of this product.
- Patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 times the upper limit of normal.
- Patients with myopathy.
- Receiving concomitant Cyclosporine.
- During pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.
WARNINGS AND PRECAUTIONS :
- As with other HMG-CoA reductase inhibitors, Rosuvastatin calcium should be used with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease.
- It is recommended that liver function tests be carried out prior to and 3 months following the initiation of treatment with Rosuvastatin calcium. Rosuvastatin calcium should be discontinued or the dose reduced if the level of serum transaminases is greater than 3 times the Upper Limit of Normal (ULN). In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephritic syndrome, the underlying disease should be treated prior to initiating therapy with Rosuvastatin calcium.
- As with other HMG-CoA reductase inhibitors, effects on skeletal muscle e.g., uncomplicated myalgia, myopathy and rarely, rhabdomyolysis, have been reported in Rosuvastatin calcium treated patients with all doses and in particular with doses > 20 mg.
- As with other HMG-CoA reductase inhibitors, the reporting rate for rhabdomyolysis in post-marketing use is higher at the highest marketed dose. Patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever. CK levels should be measured in these patients. Rosuvastatin calcium therapy should be discontinued if CK levels are markedly elevated (> 5 × ULN) or if muscular symptoms are severe and cause daily discomfort (even if CK levels are ≤ 5 × ULN). If symptoms resolve and CK levels return to normal, then consideration should be given to re-introducing Rosuvastatin calcium or an alternative HMG-CoA reductase inhibitor at the lowest dose with close monitoring. Routine monitoring of CK levels in asymptomatic patients is not warranted.
- Creatinine Kinase (CK) should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase which may confound interpretation of the result. If CK levels are significantly elevated at baseline > 5 × ULN, a confirmatory test should be carried out within 5 – 7 days. If the repeat test confirms a baseline CK > 5 × ULN, treatment should not be started.
- There was no evidence of increased skeletal muscle effects in the small number of patients dosed with Rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with fibric acid derivatives including Gemfibrozil, Cyclosporin, Nicotinic acid, Azole antifungals, protease inhibitors and Macrolide antibiotics. Gemfibrozil increases the risk of myopathy when given concomitantly with some HMG-CoA reductase inhibitors. The benefit of further alterations in lipid levels by the combined use of Rosuvastatin calcium with fibrates or Niacin should be carefully weighed against the potential risks of such combinations. The 40 mg dose is contraindicated with concomitant use of a fibrate.
- Rosuvastatin calcium should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include renal impairment, hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate, alcohol abuse, age > 70 years, situations where an increase in plasma levels may occur, and concomitant use of fibrates. In such patients the risks of treatments should be considered in relation of possible benefit and clinical monitoring is recommended. If CK levels are significantly elevated at baseline > 5 × ULN, treatment should not be started.
- Rosuvastatin calcium should not be used 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, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders or uncontrolled seizures).
- Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of Rosuvastatin calcium, in particular 40 mg. This is usually transient or intermittent, and not predictive of acute or progressive renal disease. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40 mg.
- Pregnancy and lactation : Rosuvastatin calcium is contraindicated during pregnancy or lactation as the safety of Rosuvastatin calcium during pregnancy and whilst breast-feeding has not been established. Women of child bearing potential should use appropriate contraceptive measures. Since cholesterol and other products of cholesterol biosynthesis are essential for development of the foetus, the potential risk from inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy. Animal studies provide limited evidence of reproductive toxicity. If a patient becomes pregnant during the use of this product, treatment should be discontinued immediately. Rosuvastatin calcium is excreted in the milk of rats. There are no data with respect to excretion in milk in humans.
- Effects on ability to drive and use machines : Studies to determine the effect of Rosuvastatin calcium on the ability to drive and use machines have not been conducted. However, based on its pharmacodynamic properties, Rosuvastatin calcium is unlikely to affect this ability. When driving vehicles or operating machines, it should be taken into account that dizziness may occur during treatment.
DRUG INTERACTIONS :
- Vitamin K antagonists : The initiation of treatment or dosage up-titration of Rosuvastatin calcium in patients treated concomitantly with Vitamin K antagonists (e.g., Warfarin) may result in an increase in INR. Discontinuation or down-titration of Rosuvastatin calcium may result in a decrease in INR. In such situations, appropriate monitoring of INR is desirable.
- Gemfibrozil and other lipid-lowering products : Concomitant use of Rosuvastatin calcium and Gemfibrozil resulted in a 2-fold increase in Rosuvastatin calcium Cmax and AUC. Based on data from specific interaction studies no pharmacokinetic relevant interaction with Fenofibrate is expected, however a pharmacodynamic interaction may occur. Gemfibrozil, Fenofibrate, other fibrates and lipid lowering doses > or equal to 1 g/day of Niacin (nicotinic acid) increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone. The 40 mg dose is contraindicated with concomitant use of fibrate. These patients should also start with the 5 mg dose.
- Cyclosporine : During concomitant treatment with Rosuvastatin calcium and Cyclosporine, Rosuvastatin calcium plasma levels were on average 7 times higher than those observed in healthly volunteers. Concomitant administration of Rosuvastatin calcium and Cyclosporine did not affect plasma concentrations of Cyclosporine.
- Antacids : The simultaneous dosing of Rosuvastatin calcium with an antacid suspension containing Aluminium and Magnesium hydroxide resulted in a decrease in Rosuvastatin calcium plasma concentration of approximately 50%. This effect was mitigated when the antacid was dosed 2 hours after Rosuvastatin calcium. The clinical relevance of this interaction has not been studied.
- Cytochrome P450 enzymes : No interactions have been observed between Rosuvastatin calcium and either Fluconazole (an inhibitor of CYP2C9 and CYP3A4) or Ketoconazole (an inhibitor of CYP2A6 and CYP3A4). Concomitant administration of Itraconazole (an inhibitor of CYP3A4) and Rosuvastatin calcium resulted in a 28% increase in AUC of Rosuvastatin calcium. This small increase is not considered clinically significant. Therefore, drug interaction resulting from Cytochrome P450-mediated metabolism are not expected.
- Erythromycin : Concomitant use of Rosuvastatin calcium and Erythromycin resulted in a 20% decrease in AUC(0-t) and a 30% decrease in Cmax of Rosuvastatin calcium. This interaction may be caused by the increase in gut motility caused by Erythromycin.
- Oral contraceptive/hormone replacement therapy (HRT) : Concomitant use of Rosuvastatin and an oral contraceptive resulted in an increase in Ethinyl estradiol and Norgestrel AUC of 26% and 34%, respectively. These increased plasma levels should be considered when selecting oral contraceptive doses. There are no pharmacokinetic data available in subjects taking concomitant Rosuvastatin calcium and HRT and therefore a similar effect cannot be excluded. However, the combination has been extensively used in women in clinical trials and was well tolerated.
ADVERSE REACTIONS :
- Immune system disorders : Rare : Hypersensitivity reactions including angioedema.
- Nervous system disorders : Common : Headache, dizziness.
- Gastrointestinal disorders : Common : Constipation, nausea, abdominal pain.
- Musculoskeletal, connective tissue and bone disorders : Common : Myalgia. Rare : Myopathy, including myositis and rhabdomyolysis.
- Skin disorders : Uncommon : Pruritus, rash, urticaria.
- General disorders : Common : Asthenia (the incidence of adverse drug reactions tends to increase with increasing dose).
- Skeletal muscle effects : Rare : Rhabdomyolysis which were occasionally associated with the impairment of renal function.
- Laboratory effects :
A dose-related increase in transaminases and creatinine kinase have been observed in a small number of patient taking Rosuvastatin calcium; the majority of cases were mild, asymptomatic and transient. If creatinine kinase levels are elevated (> 5 × ULN), treatment should be discontinued. Proteinuria, detected by dipstick testing and mostly tubular in origin has been observed in patients treated with Rosuvastatin calcium. Shifts in urine protein from none or trace to ++ or more at some time during treatment with 10 and 20 mg were < 1%, and approximately 3% with 40 mg. A minor increase in shift from none or trace to + was observed with the 20 mg dose. In most cases proteinuria decreases or disappears spontaneously on continued therapy and is not predictive of acute or progressive renal disease.
PRESENTATION :
| Rosuvastatin Calcium Film coated tablet 10 mg
Reg. No. GKL1902357017B1 |
Box, 10 blisters @ 10 film coated tablets |
STORAGE :
STORE BELOW 30ºC
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
