Rosuvastatin is a selective and competitive 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.
- Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface,
enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of
VLDL, thereby reducing the total number of VLDL and LDL particles.
- Maximum rosuvastatin plasma concentrations are achieved approximately 5 hours
after oral administration. The absolute bioavailability is approximately 20%.
- Rosuvastatin undergoes limited metabolism (approximately 10%). In vitro metabol-
ism studies using human hepatocytes indicate that rosuvastatin is a poor substrate
for cytochrome P450-based metabolism. The main metabolites identified are the
N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximat-
ely 50% less active than rosuvastatin whereas the lactone form is considered clini-
cally inactive. Rosuvastatin accounts for greater than 90% of the circulating
HMG-CoA reductase inhibitor activity.
- Approximately 90% of the rosuvastatin dose is excreted unchanged in the faeces
(consisting of absorbed and non-absorbed active substance) and the remaining part
is excreted in urine. The plasma elimination half-life is approximately 19 hours.
Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the
Primary hypercholesterolaemia (type IIa including heterozygous familial hypercho
lesterolaemia) or mixed dyslipidaemia (type IIb) as an adjunct to diet when response
to diet and other non-pharmacological treatments (e.g. exercise, weight reduction) is
- Homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid
lowering treatments (e.g. LDL apheresis) or if such treatments are not appropriate.
Dosage & Administration
Before treatment initiation the patient should be placed on a standard cholesterol-
lowering diet that should continue during treatment. The dose should be individual-
ised according to the goal of therapy and patient response, using current consensus
- The recommended start dose is 5 mg or 10 mg orally once daily in both statin naïve
or patients switched from another HMG CoA reductase inhibitor.
- The choice of start dose should take into account the individual patient’s cholesterol
level and future cardiovascular risk as well as the potential risk for adverse reactio-
ns. 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 cardiovas-
cular risk (in particular those 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.
- ROVISTAT® may be given at any time of day, with or without food.
- Safety and efficacy have not been established in children, therefore ROVISTAT®
is not recommended for pediatric use at this time.
- No dose adjustment is necessary.
Dosage in patients with renal insufficiency:
- No dose adjustment is necessary in patients with mild to moderate renal impairment.
The 40 mg dose is contraindicated in patients with moderate renal impairment
(creatinine clearance <60 ml/min).
- The use of ROVISTAT® in patients with severe renal impairment is contraindi
Dosage in patients with hepatic impairment:
- For patients with hepatic impairment, ROVISTAT® should be taken with caution
under specialist supervision and an assessment of liver function should be considered.
- ROVISTAT® is contraindicated in patients with active liver disease.
- 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 CK levels should be monitored. Haemodialysis is unlikely
to be of benefit.
Each film coated tablet of ROVISTAT® 10 mg contains:
Rosuvastatin 10 mg (as rosuvastatin calcium)
ROVISTAT® is contraindicated:
- In patients with hypersensitivity to rosuvastatin or to any of the excipients.
- In patients with active liver disease including unexplained, persistent elevations of
serum transaminases and any serum transaminase elevation exceeding 3 x the upper
limit of normal (ULN).
- In patients with severe renal impairment (Cr CL < 30 mL/mini).
- In patients with myopathy.
- In patients receiving concomitant cyclosporin.
- During pregnancy and lactation and in women of childbearing potential not using
appropriate contraceptive measures.
- The 40 mg dose is contraindicated in patients with pre-disposing factors for myopathy/
rhabdomyolysis. Such factors include: moderate renal impairment (creatinine clear-
ance <60 ml/min), hypothyroidism, personal or family history of hereditary muscular
disorders, previous history of muscular toxicity with another HMG-CoA reductase
inhibitor or fibrate, alcohol abuse, situations where an increase in plasma levels may
occur, Asian patients, or concomitant use of fibrates.
- Cyclosporin: During concomitant treatment with ROVISTAT® and cyclosporin,
rosuvasta-in AUC values were on average 7 times higher than those observed in healthy
- Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, the initiation
of treatment or dosage up-titration of ROVISTAT® in patients treated concomitantly
with vitamin K antagonists (e.g. warfarin) may result in an increase in International
Norma- lised Ratio (INR). Discontinuation or down-titration of rosuvastatin 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 ROVISTAT®
and gemfibrozil resulted in a 2-fold increase in rosuvastatin C-max and AUC. Gemfibro
zil, 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 a fibrate.
- Antacid: The simultaneous dosing of ROVISTAT® with an antacid suspension
containing aluminum and magnesium hydroxide resulted in a decrease in rosuvastatin
plasma concentration of approximately 50%. This effect was mitigated when the antacid
was dosed 2 hours after ROVISTAT® .
- Erythromycin: Concomitant use of ROVISTAT® and erythromycin resulted in a 20%
decrease in AUC and a 30% decrease in C-max of rosuvastatin. This interaction may be
caused by the increase in gut motility caused by erythromycin.
- Oral contraceptive/hormone replacement therapy (HRT): Concomitant use of
ROVISTAT® 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.
- Other medicinal products: Based on data from specific interaction studies no
clinically relevant interactions with digoxin is expected.
- Cytochrome P450 enzymes: Results from in vitro and in vivo studies show that
ROVISTAT® is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In
addition, ROVISTAT® is a poor substrate for these isoenzymes. No clinically relevant
interactions have been observed between rosuvastatin and either fluconazole or
ketoconazole. Concomitant administration of itraconazole and rosuvastatin resulted in
a 28% increase in AUC of rosuvastatin. This small increase is not considered clinically
significant. Therefore, drug interactions resulting from cytochrome P450-mediated
metabolism are not expected.
ROVISTAT® is contraindicated in pregnancy and lactation.
As with other HMG-CoA reductase inhibitors, the incidence of adverse drug reactions
tends to be dose dependent. The adverse events seen with ROVISTAT® are generally
mild and transient. In controlled clinical trials, less than 4% of ROVISTAT®-treated
patients were withdrawn due to adverse events
- Common: headache, dizziness, constipation, nausea, abdominal pain, myalgia,
- Uncommon: pruritus, rash and urticaria.
- Rare: hypersensitivity reactions including angioedema, myopathy and rhabdomyoly
- Renal effects: Proteinuria has been observed in patients treated with ROVISTAT®.
In most cases, proteinuria decreases or disappears spontaneously on continued
therapy, and has not been shown to be predictive of acute or progressive renal disease.
- Liver effects: As with other HMG-CoA reductase inhibitors, a dose-related increase in
transaminases has been observed in a small number of patients taking rosuvastatin; the
majority of cases were mild, asymptomatic and transient.
An assessment of renal function should be considered during routine follow-up of
patients treated with a dose of 40 mg.
- ROVISTAT®, as with other HMG-CoA reductase inhibitors, should be prescribed
with caution in patients with pre-disposing factors for myopathy / rhabdomyolysis. In
such patients the risk of treatment should be considered in relation to possible benefit
and clinical monitoring is recommended. If Creatine Kinase (CK) levels are
significantly elevated at baseline (>5xULN) treatment should not be started.
- Whilst on treatment, patients should be asked to report inexplicable muscle pain,
weakness or cramps immediately, particularly if associated with malaise or fever.
Therapy should be discontinued if CK levels are markedly elevated (>5xULN) or if
muscular symptoms are severe and cause daily discomfort (even if CK levels are
≤5xULN). If symptoms resolve and CK levels return to normal, then consideration
should be given to reintroducing ROVISTAT® or an alternative HMG-CoA reductase
inhi- bitor at the lowest dose with close monitoring. Routine monitoring of CK levels
in asymptomatic patients is not warranted.
- ROVISTAT® 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).
- As with other HMG-CoA reductase inhibitors, ROVISTAT® 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. ROVISTAT® should be discontinued
or the dose reduced if the level of serum transaminases is greater than 3 times the upper
limit of normal. In patients with secondary hypercholesterolaemia caused by
hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to
initiating therapy with ROVISTAT®.
- Pharmacokinetic studies show an increase in exposure in Asian subjects compared with
Effects on ability to drive and use machines:-
- When driving vehicles or operating machines, it should be taken into account that
dizziness may occur during treatment.
- Blister of 10 tablets, pack of 2 blisters.
- Store below 25ºC, and protect from light.