Suvardio: composition and presentation
One film-coated tablet contains 5 mg, 10 mg, 20 mg or 40 mg of rosuvastatin as the calcium salt. The four strengths exist not for convenience but because the starting dose here depends on the person more than with most medicines.
The tablet may be taken at any time of day and with or without food. The composition includes lactose, so the medicine is unsuitable for people with rare inherited metabolic disorders involving galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
How Suvardio works
Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase. That enzyme limits the rate at which 3-hydroxy-3-methylglutaryl coenzyme A is converted to mevalonate, the precursor of cholesterol, and the action of the whole statin group rests on it. Rosuvastatin works above all in the liver, which is the target organ for cholesterol-lowering medicines.
What follows is this: rosuvastatin increases the number of LDL receptors on the surface of liver cells, which makes low-density lipoproteins easier to take up and break down. At the same time it inhibits the production of VLDL in the liver, so the total number of both very-low- and low-density particles falls.
Indications
The first indication is primary hypercholesterolaemia of type IIa, including heterozygous familial, and mixed dyslipidaemia of type IIb. The medicine is prescribed to adults, adolescents and children from the age of 10 as an addition to diet, when the response to diet and other non-pharmacological measures — physical exercise, weight reduction — has proved insufficient.
The second indication is homozygous familial hypercholesterolaemia, where the medicine supplements diet and the other ways of lowering lipids, including LDL apheresis, or is used when those ways are unsuitable. The third is prevention of major cardiovascular events in people at high risk of a first such event, as an addition to correcting the other risk factors. In every case the treatment adds to the diet rather than replacing it: the standard cholesterol-lowering diet is followed before the tablets are started and kept up during treatment, and in children and adolescents the treatment is led by a specialist.
Method of use and dosage
The dose is set individually — according to current recommendations, the aim of therapy and the patient's response. The usual starting dose in hypercholesterolaemia is 5 or 10 mg once a day, both for those who have not taken statins before and for those switching from another HMG-CoA reductase inhibitor. If necessary the dose can be raised after 4 weeks.
| Who the patient is | What dose treatment starts at |
| An adult with no special circumstances | 5 or 10 mg a day; the choice takes into account the baseline cholesterol, the future cardiovascular risk and the likelihood of adverse reactions |
| Prevention of cardiovascular events | the trial that demonstrated the reduction in risk used 20 mg a day |
| Severe hypercholesterolaemia with high risk | 40 mg is considered only in the familial form and when the target is not reached on 20 mg, with routine monitoring; starting straight at 40 mg is allowed only under a specialist's supervision |
| Children and adolescents aged 10–17 | usually 5 mg a day, within a range of 5–20 mg; treatment is led by a specialist; the safety of doses above 20 mg has not been studied, the 40 mg strength is not appropriate, and for children under 10 the medicine is not recommended |
| Age over 70 | 5 mg; no other age-related adjustment is needed |
| Moderate renal impairment, creatinine clearance below 60 ml/min | 5 mg, and 40 mg is contraindicated; in severe impairment any dose is contraindicated |
| Asian ancestry | 5 mg, with 40 mg contraindicated: systemic exposure is higher in these patients |
| Predisposition to myopathy or a known genetic polymorphism | 5 mg or another reduced daily dose; in some such patients 40 mg is contraindicated |
The liver calls for separate attention. At 7 or fewer points on the Child-Pugh scale systemic exposure does not rise; at 8 or 9 points it is increased, and in such patients renal function is worth assessing too; above 9 points there is no experience at all. In active liver disease the medicine is contraindicated.
Contraindications
The general contraindications are these: hypersensitivity to rosuvastatin or to any excipient; active liver disease, including an unexplained persistent rise in aminotransferases if one of them exceeds the upper limit of normal more than threefold; severe renal impairment with creatinine clearance below 30 ml/min; myopathy; concurrent treatment with ciclosporin; pregnancy, breastfeeding, and childbearing age without effective contraception.
For the 40 mg strength the list is wider: it is contraindicated where there are factors predisposing to myopathy and rhabdomyolysis.
- moderate renal impairment with creatinine clearance below 60 ml/min;
- reduced thyroid function;
- genetically determined muscle diseases in the patient or in the family history;
- signs of muscle damage that appeared earlier on another statin or on a drug from the fibrate group;
- alcohol abuse and situations in which the plasma concentration of the medicine may rise;
- Asian ancestry and concurrent use of fibrates.
Special warnings and precautions
The main theme of the warnings is muscle. An effect on skeletal muscle has been described at every dose and especially above 20 mg: muscle pain, myopathy and rarely rhabdomyolysis, whose frequency was higher precisely at 40 mg. The patient is told to report muscle pain, loss of muscle strength or cramps at once, particularly if malaise or fever comes with them — creatine kinase activity is then measured. Treatment is stopped if it exceeds the upper limit of normal more than fivefold, or if the muscle symptoms are so pronounced that they interfere with everyday life, even at normal figures. There is no basis for routinely checking creatine kinase in people without muscle symptoms, and measuring it after intense exercise is pointless — the result will be hard to interpret.
- if the baseline creatine kinase activity exceeds normal more than fivefold, the measurement is repeated in 5–7 days and, if confirmed, treatment is not started;
- very rarely, immune-mediated necrotising myopathy has been described: proximal muscle weakness and raised creatine kinase persist even after the statin is withdrawn;
- the medicine is not used in an acute severe condition that points to myopathy or favours renal failure through rhabdomyolysis — for example sepsis, low blood pressure, major surgery, trauma, severe metabolic, hormonal and electrolyte disturbances, or uncontrolled convulsions;
- gemfibrozil is not recommended alongside it, fibrates combined with the 40 mg dose are contraindicated, and fusidic acid is not recommended at all: cases of rhabdomyolysis, some fatal, have been described.
The remaining warnings concern other organs. Liver function tests are done before treatment starts and 3 months later, and if aminotransferase activity is above three times normal the medicine is withdrawn or the dose reduced; severe hepatic events were recorded more often at the 40 mg dose, as were serious renal ones, so at that dose renal function is assessed at routine check-ups. Proteinuria, usually of tubular origin and most often transient, occurred at high doses, but it did not predict the development of kidney disease. Statins raise glucose and in people at high risk of diabetes can cause hyperglycaemia calling for diabetes care: in the JUPITER trial diabetes was recorded in 2.8% of those taking rosuvastatin against 2.3% on placebo, mostly in those whose fasting glucose was 5.6–6.9 mmol/l. Finally, with long-term statin use exceptional cases of interstitial lung tissue disease have been described — breathlessness, an unproductive cough, tiredness, weight loss and fever require treatment to be stopped.
Interactions with other medicines
Rosuvastatin is a substrate of several transport proteins, above all OATP1B1 and BCRP. Hence the main mechanism of interaction: substances that act on those proteins raise the plasma concentration of rosuvastatin and with it the likelihood of myopathy up to rhabdomyolysis.
- ciclosporin is outright a contraindication to taking the two together;
- protease inhibitors, including combinations of ritonavir with atazanavir, lopinavir or tipranavir: concurrent use is not recommended unless the rosuvastatin dose is adjusted;
- if joint prescribing is nevertheless necessary, benefit and risk are weighed, other medicines are considered, or the statin is temporarily stopped;
- with statins in general, muscle inflammation and myopathy became more frequent when they were taken together with fibric acid derivatives, nicotinic acid, antifungal azoles or macrolides;
- with ezetimibe very rare cases of rhabdomyolysis have been described, and a pharmacodynamic interaction cannot be ruled out, so the combination calls for caution.
There is also a circumstance unrelated to medicines: in patients of Asian ancestry pharmacokinetic studies show higher exposure than in Caucasians — hence both the reduced starting dose and the ban on 40 mg. In secondary hypercholesterolaemia caused by reduced thyroid function or by nephrotic syndrome, the underlying disease is treated first and only then is the statin started.
Pregnancy and breastfeeding
Use during pregnancy and breastfeeding is contraindicated, and women of childbearing age should use reliable contraception. The reasoning is direct: cholesterol and the other products of its biosynthesis are of fundamental importance for the development of the fetus, so the possible harm of inhibiting HMG-CoA reductase outweighs the benefit of treatment during pregnancy.
If pregnancy occurs while the medicine is being taken, treatment is stopped at once. Animal studies provide limited data on reproductive toxicity. Rosuvastatin is known to pass into the milk of lactating rats; there is no data on its passage into human milk.
Adverse reactions
On the whole the adverse reactions to rosuvastatin are mild and transient: fewer than 4% of participants withdrew from controlled clinical trials because of them. Headache and dizziness are counted among the common ones, and along with them diabetes, whose frequency depends on whether the person has risk factors: fasting glucose around 5.6 mmol/l and above, a body mass index over 30, raised triglycerides, hypertension in the history.
The rest occurs less often. A fall in the platelet count and hypersensitivity reactions up to angioneurotic oedema are called rare; polyneuropathy and memory loss, very rare; and with unknown frequency depression, peripheral neuropathy and sleep disorders including insomnia and nightmares have been reported. Children and adolescents aged 10–17 are noted separately: in them a tenfold excess over the upper limit of normal for creatine kinase and muscle complaints after exercise occurred more often than in adults, and observation of growth, weight and sexual maturation is limited to one year — over 52 weeks no effect on those parameters was found, but what happens with longer use is unknown.
Overdose
No specific way of treating overdose has been established.
The patient is treated symptomatically and, if needed, with supportive measures, while liver function and creatine kinase activity are monitored. Haemodialysis, on the available data, is not effective in overdose.
How to get a Suvardio prescription online
The medicine is available on prescription, and choosing the dose here is no formality: the starting dose of rosuvastatin depends on age, kidney function, ancestry and any predisposition to muscle damage. The doctor therefore needs recent lipid, creatinine and liver test results, along with information on whether you have taken statins before and how you tolerated them.
For the online consultation prepare details of liver and kidney disease, of reduced thyroid function, of inherited muscle diseases in yourself and in your family, of muscle pain on earlier statins or fibrates, of alcohol intake and of any plans for pregnancy. List the medicines you take, especially ciclosporin, anti-HIV drugs, fibrates, nicotinic acid, ezetimibe, antifungals and macrolide antibiotics. The doctor will assess these circumstances and, if there are no contraindications, will issue an electronic prescription.
