Instructions for Rosuvastatin-Teva film-coated tablets 10 mg blister No. 30
Composition
active ingredient: rosuvastatin (as rosuvastatin calcium);
1 film-coated tablet contains 5 mg or 10 mg or 20 mg of rosuvastatin as rosuvastatin calcium 5.21 mg or 10.42 mg or 20.83 mg, respectively.
excipients:
core: microcrystalline cellulose (Type 102), lactose monohydrate, crospovidone (Type B), hydroxypropylcellulose, sodium bicarbonate, magnesium stearate;
film shell:
5 mg tablets: lactose monohydrate, hypromellose 2910/6cP, titanium dioxide (E 171), triacetin, iron oxide yellow (E 172);
10 mg, 20 mg tablets: lactose monohydrate, hypromellose 2910/6cP, titanium dioxide (E 171), triacetin, red iron oxide (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties:
5 mg tablets: round, biconvex, yellow, film-coated tablets, embossed with "5" on one side and plain on the other side;
10 mg tablets: round, biconvex, pink film-coated tablets with a breakline on one side and embossed "10" on the other side;
20 mg tablets: round, biconvex, pink film-coated tablets with a breakline on one side and embossed "20" on the other side.
Pharmacotherapeutic group
Lipid-lowering agents. HMG-CoA reductase inhibitors.
ATX code C10A A07.
Pharmacological properties
Pharmacodynamics.
Mechanism of action: 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 of cholesterol (C). The primary site of action of rosuvastatin is the liver, the target organ for lowering C levels.
Rosuvastatin increases the number of LDL receptors on the surface of liver cells, enhancing the uptake and catabolism of LDL, and inhibits hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.
Pharmacodynamic effects. Rosuvastatin reduces elevated LDL-C, total cholesterol, and triglycerides (TG) and increases HDL-C. It also reduces apoB, non-LDL-C, VLDL-C, TG-VLDL-C, and increases apoA-I (Table 1). Rosuvastatin also reduces the LDL-C/HDL-C, total cholesterol/HDL-C, non-LDL-C/HDL-C, and apoB/apoA-I ratios.
Table 1
Dose response in patients with primary hypercholesterolemia types IIa and IIb
(adjusted mean percentage change from baseline)
| Dose | N | LDL-C | Total cholesterol | HDL-C | TG | Non-HDL-C | apoV | apoA-I |
| Placebo | 13 | 7 | –5 | 3 | 3 | –7 | 3 | 0 |
| 5 | 17 | 45 | 33 | 13 | 35 | 44 | 38 | 4 |
| 10 | 17 | 52 | 36 | 14 | 10 | 48 | 42 | 4 |
| 20 | 17 | 55 | 40 | 8 | 23 | 51 | 46 | 5 |
| 40 | 18 | 63 | 46 | 10 | 28 | 60 | 54 | 0 |
The therapeutic effect is achieved within 1 week after the start of the drug, 90% of the maximum effect is achieved after 2 weeks. The maximum effect is usually achieved after 4 weeks and continues thereafter.
Pharmacokinetics.
Absorption: Peak plasma concentrations of rosuvastatin are reached approximately 5 hours after oral administration. Absolute bioavailability is approximately 20%.
Distribution: Rosuvastatin is extensively taken up by the liver, which is the main site of cholesterol synthesis and LDL-C clearance. The volume of distribution of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is bound to plasma proteins, primarily albumin.
Metabolism. Rosuvastatin undergoes minor metabolism (approximately 10%). In vitro metabolism studies using human hepatocytes indicate that rosuvastatin is a poor substrate for metabolism by cytochrome P450 enzymes. The main isoenzyme involved is CYP2C9, with 2C19, 3A4 and 2D6 playing a somewhat smaller role. The main identified metabolites are the N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximately 50% less active than rosuvastatin, the lactone metabolite is considered clinically inactive. Rosuvastatin accounts for more than 90% of the circulating HMG-CoA reductase inhibitory activity.
Excretion. Approximately 90% of the rosuvastatin dose is excreted unchanged in the feces (absorbed and unabsorbed active substance together), the rest in the urine. Approximately 5% is excreted unchanged in the urine. The plasma half-life is approximately 19 hours and does not increase with increasing dose. The geometric mean plasma clearance of the drug is approximately 50 l/h (coefficient of variation - 21.7%). Hepatic uptake of rosuvastatin, as well as other HMG-CoA reductase inhibitors, occurs with the participation of the membrane transporter OATP-C, which plays an important role in the hepatic elimination of rosuvastatin.
Age and gender: There was no clinically significant effect of age or gender on the pharmacokinetics of rosuvastatin in adults. The pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolemia were similar to those in adult volunteers.
Race: Pharmacokinetic studies have shown that in patients of Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) the median AUC and Cmax values are approximately twice as high as in Caucasians; in Indians the median AUC and Cmax values are increased by approximately 1.3 times. Population pharmacokinetic analysis has not revealed any clinically significant differences between Caucasian and Negroid patients.
Renal impairment. In a study in patients with varying degrees of renal impairment, no changes in plasma concentrations of rosuvastatin or the N-desmethyl metabolite were observed in subjects with mild to moderate renal impairment. In patients with severe renal impairment (creatinine clearance < 30 ml/min), plasma concentrations of rosuvastatin were 3-fold and those of the N-desmethyl metabolite were 9-fold higher than in healthy volunteers. Steady-state plasma concentrations of rosuvastatin in patients on hemodialysis were approximately 50% higher than in healthy volunteers.
Hepatic impairment. In a study of patients with varying degrees of hepatic impairment, there was no evidence of increased exposure to rosuvastatin in patients with Child-Pugh scores of 7 or less. However, in two patients with Child-Pugh scores of 8 and 9, systemic exposure was at least twice as high as in patients with lower scores. There is no experience with rosuvastatin in patients with Child-Pugh scores greater than 9.
Genetic polymorphism. The distribution of HMG-CoA reductase inhibitors, including rosuvastatin, occurs with the participation of transport proteins OATP1B1 and BCRP. Patients with genetic polymorphisms of SLCO1B1 (OATP1B1) and/or ABCG2 (BCRP) are at risk of increased exposure to rosuvastatin. With certain forms of the SLCO1B1 p.521CC and ABCG2 p.421AA polymorphisms, rosuvastatin exposure (AUC) is increased compared to the SLCO1B1 p.521TT or ABCG2 p.421CC genotypes. Specific genotyping is not provided in clinical practice, but patients with such polymorphisms are recommended to use a lower daily dose of the drug.
Children: Two pharmacokinetic studies of rosuvastatin (tablets) in children with heterozygous familial hypercholesterolemia aged 10 to 17 years or 6 to 17 years (total of 214 patients) showed that drug exposure in children was lower than or similar to that in adult patients. Rosuvastatin exposure was predictable with respect to dose and duration of administration over 2 years of observation.
Indication
Treatment of hypercholesterolemia
Adults, adolescents and children aged 6 years and over with primary hypercholesterolemia (type IIa, including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (type IIb) as an adjunct to diet when diet and other non-pharmacological measures (e.g. exercise, weight loss) are inadequate.
Adults, adolescents and children aged 6 years and over with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering treatments (e.g. LDL apheresis) or when such treatments are inappropriate.
Prevention of cardiovascular disorders
Prevention of major cardiovascular events in patients estimated to be at high risk of a first cardiovascular event (see section 5.1), as an adjunct to correction of other risk factors.
Contraindication
The drug Rosuvastatin-Teva is contraindicated:
patients with hypersensitivity to rosuvastatin or any of the excipients of the drug;
patients with active liver disease, including those of unknown etiology, persistent elevations of serum transaminases, and any elevation of serum transaminases greater than three times the upper limit of normal (ULN);
patients with severe renal impairment (creatinine clearance < 30 ml/min);
patients with myopathy;
patients who are concurrently receiving the combination of sofosbuvir/velpatasvir/voxilaprevir;
patients who are simultaneously receiving cyclosporine;
during pregnancy or breastfeeding, as well as women of reproductive age who do not use adequate contraception.
The 40 mg dose is contraindicated in patients with a predisposition to myopathy/rhabdomyolysis. Risk factors for this include: moderate renal impairment (creatinine clearance < 60 ml/min), hypothyroidism, personal or family history of hereditary muscle diseases, history of myotoxicity with other HMG-CoA reductase inhibitors or fibrates, alcohol abuse, situations that may lead to increased plasma concentrations of the drug, belonging to the Mongoloid race, concomitant use of fibrates.
Interaction with other medicinal products and other types of interactions
Transporter protein inhibitors: Rosuvastatin is a substrate for several transporter proteins, including the hepatic uptake transporter OATP1B1 and the efflux transporter BCRP. Concomitant use of rosuvastatin with medicinal products that inhibit these transporters may result in increased plasma concentrations of rosuvastatin and an increased risk of myopathy.
During concomitant use of rosuvastatin and cyclosporine, rosuvastatin AUC values were on average approximately 7 times higher than in healthy volunteers. Rosuvastatin is contraindicated in patients receiving concomitant cyclosporine. Concomitant use did not affect cyclosporine plasma concentrations.
Although the exact mechanism of interaction is unknown, concomitant use of protease inhibitors may significantly increase rosuvastatin exposure. For example, in a pharmacokinetic study, co-administration of 10 mg of rosuvastatin and a combination product containing two protease inhibitors (300 mg atazanavir/100 mg ritonavir) in healthy volunteers was accompanied by an increase in rosuvastatin AUC and Cmax by approximately 3- and 7-fold, respectively. Concomitant use of rosuvastatin and certain combinations of protease inhibitors is possible after careful consideration of rosuvastatin dose adjustment, taking into account the expected increase in its exposure.
Gemfibrozil and other lipid-lowering agents. Concomitant use of rosuvastatin and gemfibrozil resulted in a 2-fold increase in rosuvastatin AUC and Cmax. Based on data from specific studies, a pharmacokinetically significant interaction with fenofibrate is not expected, but a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses (≥ 1 g/day) of niacin (nicotinic acid) increase the risk of myopathy when used concomitantly with HMG-CoA inhibitors, presumably because they can cause myopathy when used alone.
The 40 mg dose is contraindicated in patients receiving concomitant fibrates. These patients should also be started on the 5 mg dose.
Concomitant administration of 10 mg of rosuvastatin and 10 mg of ezetimibe to patients with hypercholesterolemia resulted in a 1.2-fold increase in rosuvastatin AUC. A pharmacodynamic interaction between rosuvastatin and ezetimibe, which could lead to adverse events, cannot be ruled out.
Concomitant administration of rosuvastatin with antacid suspensions containing aluminum or magnesium hydroxide reduced rosuvastatin plasma concentrations by approximately 50%. This effect was less pronounced when the antacid was taken 2 hours after rosuvastatin. The clinical significance of this interaction has not been studied.
Concomitant use of rosuvastatin and erythromycin decreased rosuvastatin AUC by 20% and Cmax by 30%. This interaction may be due to increased intestinal motility due to erythromycin.
In vitro and in vivo studies have shown that rosuvastatin does not inhibit or induce cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, drug interactions resulting from P450-mediated metabolism are not expected. No clinically significant interactions were observed between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4).
Ticagrelor may affect the renal excretion of rosuvastatin, increasing the risk of its accumulation. Although the exact mechanism is unknown, in some cases, the combined use of ticagrelor and rosuvastatin has led to decreased renal function, increased creatine kinase levels, and rhabdomyolysis.
Interactions requiring dose adjustment of rosuvastatin
If it is necessary to use rosuvastatin with other drugs that can increase the exposure of rosuvastatin, its dose should be adjusted. If it is expected that the exposure of the drug (AUC) will increase by approximately 2 or more times, the use of rosuvastatin should be started at a dose of 5 mg 1 time per day. The maximum daily dose of rosuvastatin should be adjusted so that the expected exposure of rosuvastatin does not exceed the exposure observed when taking a dose of 40 mg / day without the use of drugs that interact with the drug; for example, when used with gemfibrozil, the dose of rosuvastatin will be 20 mg (an increase in exposure of 1.9 times), when used with the combination of ritonavir / atazanavir - 10 mg (an increase of 3.1 times).
If the drug increases the AUC of rosuvastatin by less than 2 times, the initial dose does not need to be reduced, but caution should be exercised when increasing the dose of rosuvastatin to more than 20 mg.
Table 2
Effect of concomitant medications on rosuvastatin exposure
(AUC; in descending order of magnitude) from published clinical trial data
| Increase in rosuvastatin AUC by 2-fold or more than 2-fold |
| Dosing regimen of the interacting drug | Rosuvastatin dosage regimen | Changes in rosuvastatin AUC* |
Sofosbuvir/velpatasvir/voxilaprevir (400 mg-100 mg-100 mg) + voxilaprevir (100 mg) once a day for 15 days | 10 mg, single dose | ↑ 7.4 times |
| Cyclosporine 75 mg twice daily to 200 mg twice daily, 6 months | 10 mg once daily, 10 days | ↑ 7.1 times |
Darolutamide 600 mg twice daily, 5 days | 5 mg, single dose | ↑ 5.2 times |
Regorafenib 160 mg once daily, 14 days | 5 mg, single dose | ↑ 3.8 times | | Atazanavir 300 mg/ritonavir 100 mg once daily, 8 days | 10 mg, single dose | ↑ 3.1 times |
| Velpatasvir 100 mg once daily | 10 mg, single dose | ↑ 2.7 times |
| Ombitasvir 25 mg/paritaprevir 150 mg/ritonavir 100 mg once daily/dasabuvir 400 mg twice daily, 14 days | 5 mg, single dose | ↑ 2.6 times |
| Grazoprevir 200 mg/elbasvir 50 mg once daily, 11 days | 10 mg, single dose | ↑ 2.3 times |
| Glecaprevir 400 mg/pibrentasvir 120 mg once daily, 7 days | 5 mg once daily, 7 days | ↑ 2.2 times |
| Lopinavir 400 mg/ritonavir 100 mg twice daily, 17 days | 20 mg once daily, 7 days | ↑ 2.1 times |
| Clopidogrel 300 mg, then 75 mg 24 hours later | 20 mg, single dose | ↑ 2 times |
| Gemfibrozil 600 mg twice daily, 7 days | 80 mg, single dose | ↑ 1.9 times |
| Increase in rosuvastatin AUC less than 2-fold |
| Dosing regimen of the interacting drug | Rosuvastatin dosage regimen | Changes in rosuvastatin AUC* |
| Eltrombopag 75 mg once daily, 5 days | 10 mg, single dose | ↑ 1.6 times |
| Darunavir 600 mg/ritonavir 100 mg twice daily, 7 days | 10 mg once daily, 7 days | ↑ 1.5 times |
| Tipranavir 500 mg/ritonavir 200 mg twice daily, 11 days | 10 mg, single dose | ↑ 1.4 times |
| Dronedarone 400 mg twice daily | Unknown | ↑ 1.4 times |
| Itraconazole 200 mg once daily, 5 days | 10 mg, single dose | ↑ 1.4 times ** |
| Ezetimibe 10 mg once daily, 14 days | 10 mg once daily, 14 days | ↑ 1.2 times ** |
| Decrease in rosuvastatin AUC |
| Dosing regimen of the interacting drug | Rosuvastatin dosage regimen | Changes in rosuvastatin AUC* |
| Erythromycin 500 mg four times a day, 7 days | 80 mg, single dose | ↓ 20% |
| Baicalin 50 mg three times a day, 14 days | 20 mg, single dose | ↓ 47% |
* Data presented as x-fold change represents the ratio between rosuvastatin in combination and alone. Data presented as % change represents the % difference relative to rosuvastatin alone.
Increase is indicated by the ↑ icon, decrease by the ↓ icon.
** Several interaction studies have been conducted at different doses of rosuvastatin, the most significant relationship is shown in the table.
Drugs/combinations that did not have a clinically significant effect on the AUC ratio of rosuvastatin when used simultaneously: aleglitazar 0.3 mg for 7 days; fenofibrate 67 mg for 7 days 3 times a day; fluconazole 200 mg for 11 days 1 time a day; fosamprenavir 700 mg/ritonavir 100 mg for 8 days 2 times a day; ketoconazole 200 mg for 7 days 2 times a day; rifampin 450 mg for 7 days 1 time a day; silymarin 140 mg for 5 days 3 times a day.
Effect of rosuvastatin on concomitant medications
As with other HMG-CoA reductase inhibitors, when starting or increasing the dose of rosuvastatin in patients receiving concomitant vitamin K antagonists (e.g. warfarin or other coumarin anticoagulants), an increase in the international normalized ratio (INR) may occur. Discontinuation of rosuvastatin or dose reduction may lead to a decrease in INR. In such cases, appropriate monitoring of INR is advisable.
Oral contraceptives/hormone replacement therapy (HRT). Concomitant use of rosuvastatin and oral contraceptives resulted in an increase in the AUC of ethinylestradiol and norgestrel by 26% and 34%, respectively. This increase in plasma levels should be considered when selecting the dose of oral contraceptives. There are no data on the pharmacokinetics of drugs in patients taking rosuvastatin and HRT simultaneously, so a similar effect cannot be excluded. However, the combination has been widely used in women in clinical trials and was well tolerated.
Other medicines
Based on specific interaction studies, no clinically significant interaction with digoxin is expected.
Interaction studies of rosuvastatin with fusidic acid have not been conducted. The risk of myopathy, including rhabdomyolysis, may be increased when fusidic acid is administered concomitantly with statins. The mechanism of this interaction (pharmacodynamic or pharmacokinetic, or both) is not yet known. Cases of rhabdomyolysis (including fatal cases) have been reported in patients receiving this combination. If systemic treatment with fusidic acid is necessary, rosuvastatin should be discontinued for the duration of fusidic acid treatment.
Children: Interaction studies have only been conducted in adults. The extent of interaction in children is unknown.
Application features
Renal Effects: Proteinuria (detected by dipstick analysis), predominantly of tubular origin and in most cases transient or intermittent, has been observed in patients receiving high doses of rosuvastatin, particularly 40 mg. Proteinuria was not a marker of acute or progressive renal disease. The frequency of reports of serious renal events in post-marketing studies is higher with the 40 mg dose. Patients receiving the 40 mg dose should have their renal function monitored regularly.
Skeletal muscle disorders (e.g. myalgia, myopathy and rarely rhabdomyolysis) have been reported in patients taking rosuvastatin at all doses, particularly above 20 mg. Very rare cases of rhabdomyolysis have been reported when ezetimibe was used in combination with HMG-CoA reductase inhibitors. The possibility of a pharmacodynamic interaction cannot be excluded, and such a combination should be used with caution.
As with other HMG-CoA reductase inhibitors, the incidence of rhabdomyolysis associated with rosuvastatin in the post-marketing period was higher at the 40 mg dose.
Creatine kinase (CK) levels should not be measured after significant exercise or in the presence of possible alternative causes of elevated CK that may complicate interpretation of results.
If baseline CK levels are significantly elevated (> 5 × ULN), a repeat test should be performed within 5–7 days to confirm the results. If the repeat test results confirm a baseline CK value > 5 × ULN, rosuvastatin should not be initiated.
Before starting treatment. Rosuvastatin, like other HMG-CoA reductase inhibitors, should be prescribed with caution to patients with a predisposition to myopathy/rhabdomyolysis. Risk factors for this include: impaired renal function, hypothyroidism, personal or family history of hereditary muscle diseases, history of myotoxicity with other HMG-CoA reductase inhibitors or fibrates, age > 70 years, alcohol abuse, situations that may lead to increased plasma levels of the drug, concomitant use of fibrates. In such patients, the risk associated with treatment should be assessed in comparison with the expected benefit; clinical monitoring is also recommended. If baseline CK levels are significantly elevated (> 5 × ULN), treatment should not be started.
During treatment. Patients should be asked to report unexplained muscle pain, weakness or cramps immediately, especially if accompanied by malaise or fever. In such patients, CK levels should be measured. The drug should be discontinued if CK levels are significantly elevated (> 5 × ULN) or if muscle symptoms are severe and cause daily discomfort (even if CK levels are ≤ 5 × ULN). If symptoms resolve and CK levels return to normal, rosuvastatin or an alternative HMG-CoA reductase inhibitor can be restarted at the lowest dose and under close supervision. There is no need to regularly monitor CK levels in asymptomatic patients. Very rare cases of immune-mediated necrotizing myopathy (IMNM) have been reported during or after treatment with statins, including rosuvastatin. Clinical manifestations of IONM include proximal muscle weakness and elevated serum CK levels, which persist even after discontinuation of statins.
In clinical studies, there was no evidence of increased effects on skeletal muscle in a small number of patients taking rosuvastatin and concomitant medications. However, an increased incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when used concomitantly with some HMG-CoA inhibitors. Therefore, the use of rosuvastatin in combination with gemfibrozil is not recommended. The benefits of further lipid-lowering effects when rosuvastatin is used in combination with fibrates or niacin should be carefully weighed against the potential risks associated with the use of such combinations. The 40 mg dose is contraindicated with concomitant use of fibrates.
Rosuvastatin should not be used in patients with acute, serious conditions that suggest myopathy or the possibility of developing renal failure secondary to rhabdomyolysis (such as sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders or uncontrolled seizures).
Myasthenia gravis, ocular myasthenia. Statins have been reported to cause de novo or exacerbate pre-existing myasthenia gravis or ocular myasthenia in a few cases. If symptoms worsen, the drug should be discontinued. Relapses have been reported with re-administration of the same or a different statin.
Hepatic effects. As with other HMG-CoA reductase inhibitors, rosuvastatin should be used with caution in patients who abuse alcohol and/or have a history of liver disease. It is recommended to check biochemical parameters of liver function before starting treatment and 3 months later. Rosuvastatin should be discontinued or the dose reduced if serum transaminase levels exceed three times the upper limit of normal. The frequency of reports of serious hepatic events (predominantly increased hepatic transaminases) in the post-marketing period was higher with the 40 mg dose.
In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the underlying disease should be treated first before initiating therapy with rosuvastatin.
Race: Pharmacokinetic studies indicate an increase in exposure in patients of Mongoloid race of approximately two times compared to Caucasians.
Protease inhibitors: Increased systemic exposure to rosuvastatin has been observed in patients receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. The lipid-lowering benefits of rosuvastatin in HIV-infected patients receiving protease inhibitors should be weighed against the potential for increased plasma levels of rosuvastatin at the start of therapy and during dose titration of rosuvastatin. Co-administration of the medicinal product with protease inhibitors is not recommended unless the dose of rosuvastatin is adjusted.
Interstitial lung disease: Exceptional cases of interstitial lung disease have been reported with some statins, particularly with long-term treatment. Symptoms may include shortness of breath, non-productive cough, and general malaise (fatigue, weight loss, and fever). If interstitial lung disease is suspected, statins should be discontinued.
Diabetes mellitus. There is some evidence that statins, as a class, increase blood glucose levels and in some patients at high risk of future diabetes, may cause hyperglycaemia to a level requiring appropriate diabetes management. However, this risk is outweighed by the reduced risk of vascular events with statins and should not be a reason to discontinue statin therapy. Patients at risk (fasting glucose 5.6–6.0 mmol/l, BMI > 30 kg/m2, elevated triglycerides, hypertension) should be monitored clinically and biochemically according to national guidelines.
In the JUPITER study, the overall incidence of diabetes mellitus was 2.8% in the rosuvastatin group and 2.3% in the placebo group, predominantly in patients with fasting glucose levels in the range of 5.6–6.9 mmol/L.
Severe cutaneous adverse reactions. Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported with rosuvastatin. When prescribing rosuvastatin, patients should be informed of the signs and symptoms of severe cutaneous reactions and monitored closely. If signs and symptoms suggestive of these reactions appear, rosuvastatin should be discontinued immediately and alternative treatment should be considered.
If a patient develops a serious reaction such as SJS or DRESS while taking rosuvastatin, treatment with rosuvastatin should not be resumed in that patient at any time.
Children: Assessment of linear growth (height), body weight, BMI, and secondary Tanner puberty characteristics in children aged 6 to 17 years who received rosuvastatin was limited to a 2-year period. After 2 years of study treatment, no effect on height, body weight, BMI, or puberty was observed.
In a clinical study in children and adolescents taking rosuvastatin for 52 weeks, an increase in CK levels more than 10 times the upper limit of normal and muscle symptoms after physical exertion or increased physical activity were observed more often compared to those in adults.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, i.e. essentially ‘sodium-free’.
Use during pregnancy or breastfeeding
Women of reproductive age should use adequate contraception.
Since cholesterol and other cholesterol biosynthesis products play an essential role in fetal development, the potential risk of inhibition of HMG-CoA reductase outweighs the benefits of using the drug during pregnancy. Animal data on reproductive toxicity are limited. If the patient becomes pregnant while taking this drug, treatment should be discontinued immediately.
Rosuvastatin is excreted in the milk of rats. There is no data on the penetration of the drug into human breast milk.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effect of rosuvastatin on the ability to drive and use machines have not been conducted. Given its pharmacodynamic properties, it is unlikely that rosuvastatin will affect this ability. When driving or operating machinery, the possibility of dizziness should be taken into account during treatment.
Method of administration and doses
Before starting treatment, the patient should be placed on a standard cholesterol-lowering diet and should continue to follow it throughout treatment. The dose should be individualised according to the patient's goals and response to treatment, in accordance with current guidelines.
The drug Rosuvastatin-Teva can be taken at any time of the day, regardless of meals.
Treatment of hypercholesterolemia
The recommended starting dose is 5 or 10 mg orally once daily for both statin-naive patients and those switching from another HMG-CoA reductase inhibitor. The starting dose should take into account the individual patient's cholesterol levels and the risk of future cardiovascular events, as well as the likelihood of adverse reactions. If necessary, the dose can be increased to the next level after 4 weeks. Given that adverse reactions occur more frequently with the 40 mg dose than with lower doses, final titration to 40 mg should only be considered in patients with severe hypercholesterolemia and high risk of cardiovascular events (particularly in patients with familial hypercholesterolemia) who have not achieved their treatment goal with the 20 mg dose and who will be monitored regularly. Specialist supervision is recommended when initiating the 40 mg dose.
Prevention of cardiovascular disorders
In the study to reduce the risk of cardiovascular disorders, the drug was used at a dose of 20 mg per day.
Elderly patients: The recommended starting dose for patients > 70 years of age is 5 mg. No other dose adjustment is necessary based on age.
No dose adjustment is required for patients with mild or moderate renal impairment. The recommended starting dose for patients with moderate renal impairment (creatinine clearance < 60 ml/min) is 5 mg. The 40 mg dose is contraindicated in patients with moderate renal impairment. Rosuvastatin is contraindicated in patients with severe renal impairment at any dose.
In patients with impaired liver function, estimated at 7 or less points on the Child-Pugh scale, an increase in systemic exposure to rosuvastatin was not observed. However, in individuals with impairments of 8 and 9 points on the Child-Pugh scale, systemic exposure increased. In such patients, it is advisable to assess renal function. There is no experience of using the drug in patients with impaired liver function above 9 points on the Child-Pugh scale.
