Zahron: composition and dosage form
One film-coated tablet contains 5 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg of rosuvastatin as the calcium salt. Six strengths is more than most statins have, and two of them, 15 and 30 mg, are rarely seen.
The medicine may be taken at any time of day, with or without food. There is one further condition, and it does not concern the tablet: both before treatment starts and during it, the patient should follow a diet aimed at lowering cholesterol.
How Zahron works
Rosuvastatin is a selective competitive inhibitor of HMG-CoA reductase, the enzyme that sets the rate at which 3-hydroxy-3-methylglutaryl coenzyme A is converted into mevalonate, the precursor of cholesterol. It acts above all in the liver — the target organ for cholesterol-lowering medicines.
After that two mechanisms work at once, and that is where it differs from a simple "blocked the enzyme, cholesterol fell". Rosuvastatin increases the number of LDL receptors on the surface of liver cells, which makes the uptake and catabolism of LDL easier. At the same time it inhibits the production of very low density lipoproteins in the liver. The result is made of two parts: the total amount of both LDL and VLDL falls.
Indications
Here begins the feature this medicine has and most statins do not: the indications are worded separately for the different strengths, and they differ not in nuance but in the age from which the medicine may be used. The 5, 10, 20 and 40 mg strengths are addressed to adults and cover primary hypercholesterolaemia of type IIa and mixed dyslipidaemia of type IIb, as an addition to diet, when diet itself and other non-pharmacological measures — physical exercise, weight reduction — prove insufficient. The 15 and 30 mg strengths carry the same indication, but the group of patients is wider: adults, adolescents and children from the age of six, and primary hypercholesterolaemia here expressly includes the heterozygous familial form.
The two remaining indications are common to all strengths. The first is homozygous familial hypercholesterolaemia, where the medicine comes as an addition to diet and to other lipid-lowering methods such as LDL apheresis, or is used when those methods are unsuitable. The second is the prevention of major cardiovascular events in people whose risk of a first such event is assessed as high; it works not on its own but together with correcting the other risk factors. The practical conclusion from that division is simple: the 15 and 30 mg strengths exist not to provide intermediate values but for children and adolescents — for adults the step between 10 and 20 mg is quite enough.
Method of administration and dosage
The recommended starting dose in hypercholesterolaemia is 5 or 10 mg by mouth once a day, the same for patients who have never taken statins and for those who were on other HMG-CoA reductase inhibitors. In choosing it, the particular patient's cholesterol, their future risk of cardiovascular disease and the risk of adverse reactions are all taken into account. If necessary, the dose may be raised after 4 weeks of treatment. In the studies on reducing cardiovascular risk, 20 mg a day was used.
The 40 mg dose deserves a conversation of its own. Adverse reactions occur more often on it than on smaller doses, so raising to the maximum of 40 mg is considered only in patients with severe hypercholesterolaemia in the high cardiovascular risk group — above all with the familial form — in whom the treatment target was not reached on 20 mg. Such patients stay under routine monitoring, and treatment with 40 mg is recommended to be supervised by a specialist. The other groups change not so much the dose as its starting value: patients over 70 are advised to begin with 5 mg, and with moderate renal impairment at a creatinine clearance below 60 ml/min also with 5 mg, while in mild to moderate impairment no dose change is needed at all. In severe renal impairment the medicine is contraindicated. For the liver the reference is the Child-Pugh scale: at 7 points or fewer systemic exposure did not increase, at 8–9 points it did, and in those patients kidney function is worth assessing, while for patients above 9 points there are no data at all. In children treatment is directed by a specialist, and below the age of 10 the medicine is not recommended: experience is limited to a small number of children aged 8 to 10 with the homozygous familial form.
Contraindications
The general list of prohibitions runs as follows: hypersensitivity to rosuvastatin or to the excipients; active liver disease, including an unexplained persistent rise in serum aminotransferase activity more than three times the upper limit of normal in at least one of them; severe renal impairment with a creatinine clearance below 30 ml/min; myopathy; concurrent treatment with ciclosporin. Pregnancy, breastfeeding and any woman of childbearing age not using effective contraception belong here too.
And then comes what makes this medicine unlike other statins: the 40 mg dose has a contraindication list of its own. It is forbidden in patients with factors predisposing to myopathy or rhabdomyolysis, and there are eight such factors: moderate renal impairment with a creatinine clearance below 60 ml/min, hypothyroidism, genetically determined muscle disease in the patient or in family members, muscle damage after another HMG-CoA reductase inhibitor or after a fibrate, alcohol abuse, situations in which the blood concentration of the medicine may rise, Asian origin, and concurrent use of fibrates. Asian origin is on that list for a reason: pharmacokinetic studies showed higher exposure in such patients than in Caucasians.
Special warnings and precautions
Muscles are the central theme of the warnings, and the set of risk factors here is the same as in the list for the 40 mg dose, plus age above 70. Rosuvastatin, like other HMG-CoA reductase inhibitors, is capable of causing muscle pain, myopathy and rarely rhabdomyolysis, and the frequency of its adverse reactions shows dose dependence. Hence the caution in those who abuse alcohol and in those with liver disease in their history.
- kidneys: in patients on large doses, particularly on 40 mg, transient or occasional proteinuria was seen, mainly of tubular origin, detected by dipstick; the data did not show that it precedes acute or progressive kidney disease;
- lungs: in rare cases interstitial lung disease has been reported with statins, especially during long-term therapy;
- blood sugar: some data indicate that statins raise glucose and that in some patients at high risk of developing diabetes they may cause hyperglycaemia requiring appropriate treatment;
- Asian origin: the higher exposure to the medicine compared with Caucasians is the reason the 40 mg dose is contraindicated in such patients.
The proteinuria figures are worth quoting, because they show the dose dependence clearly. On doses of 10–20 mg a shift in the urine protein result from "none" or "trace" to "++" or more was recorded in fewer than 1% of patients, and on the 40 mg dose in 3%. After 20 mg the changes were smaller: from "none" or "trace" to "+". In most cases the proteinuria diminishes or passes during treatment.
Interaction with other medicines
The strictest interaction has been moved into the contraindications: ciclosporin is not combined with rosuvastatin at all. The other combinations are dangerous not in themselves but because they raise the blood concentration of the medicine — and that, as the previous sections show, is the main risk factor for muscle damage.
| With what | What happens | What to do |
| Ciclosporin | a considerable rise in exposure to rosuvastatin | the combination is contraindicated |
| Fibrates, gemfibrozil included | an increased risk of myopathy and rhabdomyolysis | the 40 mg dose is contraindicated when fibrates are taken at the same time |
| Situations that raise the blood concentration of the medicine | the risk of muscle damage grows along with the concentration | treat as a factor predisposing to myopathy and do not give 40 mg |
| Other HMG-CoA reductase inhibitors in the history | if muscle damage already occurred on them, the risk persists here too | the 40 mg dose is contraindicated |
Hypothyroidism stands apart — not a medicine but a state from that same list of risk factors, and it is worth detecting before treatment begins rather than after muscle pain appears. The general logic is this: before prescribing, the doctor goes through the list of eight points, and if even one of them matches, the dose ceiling for that patient is 20 mg.
Pregnancy and breastfeeding
Use of the preparation during pregnancy and breastfeeding is contraindicated, and patients of childbearing age should use effective contraception. The reasoning here is not statistical but biological: cholesterol and the other products of its metabolism are necessary for the normal development of the fetus, so the expected risk of using HMG-CoA reductase inhibitors outweighs the benefit of treating a pregnant woman.
Animal studies showed a harmful effect on reproduction and, as a precaution, avoiding the medicine during pregnancy is recommended. About breastfeeding little is known: rosuvastatin passes into the milk of lactating rats, and there are no data on its passage into the milk of breastfeeding women.
Adverse effects
The overall assessment is a calm one: the unwanted effects of rosuvastatin are most often mild and transient, and fewer than 4% of patients dropped out of controlled clinical trials because of them. The frequency does, however, show dose dependence — as with other HMG-CoA reductase inhibitors.
- common: headache and dizziness, constipation, nausea, abdominal pain, muscle pain, weakness, and also diabetes;
- uncommon: itching, rash, urticaria;
- rare: thrombocytopenia, hypersensitivity reactions up to angioedema, a rise in hepatic aminotransferase activity, pancreatitis, myopathy including inflammation of the eye muscle, and rhabdomyolysis;
- very rare: on the nervous side, polyneuropathy and memory disturbances; on the liver side, jaundice and its inflammation; besides these, joint pain, blood in the urine and breast enlargement in men;
- unknown frequency: depression, peripheral neuropathy, sleep disturbances with insomnia and nightmares, cough and breathlessness, diarrhoea, Stevens-Johnson syndrome, immune-mediated necrotising myopathy and tendon injuries.
Diabetes stands apart on that list because it landed in the common category. It is the same hyperglycaemia the precautions section warns about: statins raise glucose levels, and in patients at high risk of developing diabetes that may call for treatment of its own. The conclusion is not "give up the statin" but "check the blood sugar before starting and keep an eye on it afterwards".
Overdose
The product information admits it plainly: how to act in a rosuvastatin overdose has not been established. What remains is symptomatic treatment and, if necessary, supportive treatment.
Two parameters are monitored without exception — liver function and creatine kinase activity, that is, exactly the two target organs around which all the warnings are built. And one limitation: haemodialysis has no place in treating an overdose.
How to get a prescription for Zahron online
Rosuvastatin has a list of eight factors, each of which closes the door on the 40 mg dose: the kidneys, the thyroid, muscle disease in the family, past muscle trouble on statins or fibrates, alcohol, fibrates being taken now, Asian origin, and anything that raises the blood concentration of the medicine. The doctor goes through that list before prescribing, not after the first complaints about muscles. On e-zdrowie.com you fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
Begin the questionnaire with muscles and kidneys: whether you have had muscle pain or weakness on statins or fibrates before, whether hereditary muscle disease runs in you or your relatives, and what your latest creatinine or creatinine clearance is. Give your thyroid function separately, and how much alcohol you drink — both points come from that same list. Provide your lipid profile with total cholesterol and LDL, the date of the test, and ALT with AST: with a persistent threefold rise the medicine is contraindicated. Be sure to report whether you take ciclosporin — a direct contraindication — and fibrates. Say how long you have been on a low-cholesterol diet: the medicine supplements it, it does not replace it. Women of childbearing age must state their contraceptive method: without one rosuvastatin is not prescribed.
