Rosuvastatin Mylan 5mg 10mg 20mg & 40mg Film-coated Tablets

  • Name:

    Rosuvastatin Mylan 5mg 10mg 20mg & 40mg Film-coated Tablets

  • Company:
    info
  • Active Ingredients:

    Rosuvastatin Calcium

  • Legal Category:

    Product subject to medical prescription which may be renewed (B)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 13/09/19

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Summary of Product Characteristics last updated on medicines.ie: 13/9/2019

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Gerard Laboratories

Gerard Laboratories

Company Products

Medicine NameActive Ingredients
Medicine Name Abacavir/Lamivudine Mylan 600 mg/300 mg film-coated tablets Active Ingredients Abacavir hydrochloride, Lamivudine
Medicine Name Agerdex 1mg Film Coated Tablets Active Ingredients Anastrozole
Medicine Name Agomelatine Mylan 25 mg film-coated tablets Active Ingredients Agomelatine
Medicine Name Amisulpride 50mg & 200mg Tablets Active Ingredients Amisulpride
Medicine Name Amlodipine Mylan 5mg & 10mg Tablets Active Ingredients Amlodipine besilate
Medicine Name Areloger 7.5mg & 15mg Tablets Active Ingredients Meloxicam
Medicine Name Aripil 5mg & 10mg Film-coated Tablets Active Ingredients Donepezil Hydrochloride
Medicine Name Atenetic 50/12.5mg & 100/25mg Film - coated Tablets Active Ingredients Atenolol, Chlortalidone
Medicine Name Atorvastatin Mylan 10 mg, 20 mg, 40 mg & 80 mg film-coated tablets Active Ingredients Atorvastatin calcium trihydrate
Medicine Name Atovaquone/Proguanil Hydrochloride 250 mg/100 mg film-coated tablets Active Ingredients Atovaquone, Proguanil Hydrochloride
Medicine Name Azromax 250mg Film-coated tablets Active Ingredients Azithromycin monohydrate
Medicine Name Baclopar Tablets 10 mg Active Ingredients Baclofen
Medicine Name Bisoprolol Mylan Active Ingredients Bisoprolol Fumarate
Medicine Name Brabio 20mg/ml solution for injection, pre-filled syringe Active Ingredients Glatiramer Acetate
Medicine Name Brabio 40mg/ml solution for injection, pre-filled syringe Active Ingredients Glatiramer Acetate
Medicine Name Cifloxager 250 mg Film-coated Tablets Active Ingredients Ciprofloxacin hydrochloride
Medicine Name Cifloxager 500 mg Film-coated Tablets Active Ingredients Ciprofloxacin hydrochloride
Medicine Name Ciprager 10mg & 20mg Film Coated Tablets Active Ingredients citalopram hydrobromide
Medicine Name Ciprager 40mg Film Coated Tablets Active Ingredients citalopram hydrobromide
Medicine Name Ciprofloxacin Mylan 2mg/1ml solution for infusion Active Ingredients Ciprofloxacin
Medicine Name Clopidogrel Mylan 75 mg film-coated tablets Active Ingredients clopidogrel hydrochloride
Medicine Name Darunavir Mylan 800 mg film-coated tablets Active Ingredients darunavir ethanolate
Medicine Name Depreger 50mg & 100mg Film-Coated Tablets Active Ingredients sertraline hydrochloride
Medicine Name Diaclide MR 30 mg Modified-release Tablets Active Ingredients Gliclazide
Medicine Name Diaclide MR 60mg modified-released tablets Active Ingredients Gliclazide
1 - 0 of 116 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 13 September 2019 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 13 September 2019 PIL

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 17 July 2019 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 4 - possible side effects
  • Change to section 6 - what the product looks like and pack contents
  • Change to section 6 - date of revision

Updated on 17 July 2019 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 15 February 2018 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 15 February 2018 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.5 - Nature and contents of container

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 5 mg rosuvastatin (as rosuvastatin calcium).
Excipients with known effect:
Lactose monohydrate: Each 5 mg film-coated tablet contains 13.1 12.4 mg lactose monohydrate.
Allura Red: Each 5 mg film-coated tablet contains 0.003 mg Allura Red.

Each film-coated tablet contains 10 mg rosuvastatin (as rosuvastatin calcium).
Excipients with known effect:
Lactose monohydrate: Each 10 mg film-coated tablet contains 26.2 24.9 mg lactose. monohydrate.
Sunset yellow: Each 10 mg film-coated tablet contains 0.009 mg Sunset Yellow.
Allura Red: Each 10 mg film-coated tablet contains 0.010 mg Allura Red.

Each film-coated tablet contains 20mg rosuvastatin (as rosuvastatin calcium).
Excipients with known effect:
Lactose monohydrate: Each 20 mg film-coated tablet contains 52.4 49.8 mg lactose monohydrate.
Sunset yellow: Each 20 mg film-coated tablet contains 0.018 mg Sunset Yellow.
Allura Red: Each 20 mg film-coated tablet contains 0.020 mg Allura Red.

Each film-coated tablet contains 40mg rosuvastatin (as rosuvastatin calcium).
Excipients with known effect:
Lactose monohydrate: Each 40 mg film-coated tablet contains 104.8 99.6 mg lactose monohydrate.
Sunset yellow: Each 40 mg film-coated tablet contains 0.036 mg Sunset Yellow.
Allura Red: Each 40 mg film-coated tablet contains 0.04 mg Allura Red.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet

5 mg: A yellow, film-coated, round, biconvex, film-coated tablet of 4.3 mm diameter, debossed with “‘M’” on one side and “‘RS’” on the other side.

10 mg: A pink, film-coated, round, biconvex, film-coated tablet of 5.55 mm diameter, debossed with “‘M’” on one side and ‘“RS1’” on the other side.

20 mg: A pink, film-coated, round, biconvex, film-coated tablet of 7.14 mm diameter, debossed with “‘M’” on one side and ‘“RS2’” on the other side.

40 mg: A pink, film-coated, oval, biconvex, film-coated tablet of 11.5 mm x 7 mm dimension, debossed with “‘M’” on one side and ‘“RS4’” on the other side.

4.1 Therapeutic indications

Treatment of hypercholesterolaemia
Adults, adolescents and children aged 6 years or older with primary hypercholesterolaemia (type IIa including heterozygous familial hypercholesterolaemia) 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 inadequate.

Adults, adolescents and children aged 6 years or older with Hhomozygous familial hypercholesterolaemia as an adjunct to diet and other lipid lowering treatments (e.g. LDL apheresis) or if such treatments are not appropriate.

4.2 Posology and method of administration

Before treatment initiation the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment. The dose should be individualised according to the goal of therapy and patient response, using current consensus guidelines.

Rosuvastatin Mylan may be given at any time of day, with or without food.

Children and adolescents 6 to 17 years of age (Tanner Stage <II-V)

Heterozygous familial hypercholesterolaemia

In children and adolescents with heterozygous familial hypercholesterolaemia the usual start dose is 5 mg daily.

• In children 6 to 9 years of age with heterozygous familial hypercholesterolaemia, the usual dose range is 5-10 mg orally once daily. Safety and efficacy of doses greater than 10 mg have not been studied in this population.
• In children 10 to 17 years of age with heterozygous familial hypercholesterolaemia, the usual dose range is 5-20 mg orally once daily. Safety and efficacy of doses greater than 20 mg have not been studied in this population.

Titration should be conducted according to the individual response and tolerability in paediatric patients, as recommended by the paediatric treatment recommendations (see section 4.4). Children and adolescents should be placed on standard cholesterol-lowering diet before rosuvastatin treatment initiation; this diet should be continued during rosuvastatin treatment.

Homozygous familial hypercholesterolaemia
Experience iIn children 6 to 17 years of age with homozygous familial hypercholesterolaemia, is limited to a small number of children aged between 8 and 17 years the recommended maximum dose is 20 mg once daily.

A starting dose of 5 to 10 mg once daily depending on age, weight and prior statin use is advised. Titration to the maximum dose of 20 mg once daily should be conducted according to the individual response and tolerability in paediatric patients, as recommended by the paediatric treatment recommendations (see section 4.4). Children and adolescents should be placed on standard cholesterol-lowering diet before rosuvastatin treatment initiation; this diet should be continued during rosuvastatin treatment.

There is limited experience with doses other than 20 mg in this population.

The 40 mg tablet is not suitable for use in paediatric patients.

Children younger than 6 years
The safety and efficacy of use in children younger than 6 years has not been studied. Therefore, Rosuvastatin Mylan is not recommended for use in children younger than 6 years.

4.3 Contraindications

Rosuvastatin Mylan is contraindicated:
-  in patients with hypersensitivity to rosuvastatin or to any of the excipients listed in section 6.1.
-  in patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x times the upper limit of normal (ULN).
-  in patients with severe renal impairment (creatinine clearance <30 ml/min).
-  in patients with myopathy.
-  in patients receiving concomitant ciclosporin.
-  during pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.

4.4 Special warnings and precautions for use

Renal Effects
Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of Rosuvastatinrosuvastatin, in particular 40 mg, where it was transient or intermittent in most cases. Proteinuria has not been shown to be predictive of acute or progressive renal disease (see section 4.8). The reporting rate for serious renal events in post-marketing use is higher at the 40 mg dose. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40 mg.

Skeletal Muscle Effects
Effects on skeletal muscle e.g. myalgia, myopathy and, rarely, rhabdomyolysis have been reported in Rosuvastatin rosuvastatin-treated patients with all doses and in particular with doses > 20 mg. Very rare cases of rhabdomyolysis have been reported with the use of ezetimibe in combination with HMG-CoA reductase inhibitors. A pharmacodynamic interaction cannot be excluded (see section 4.5) and caution should be exercised with their combined use.

As with other HMG-CoA reductase inhibitors, the reporting rate for rhabdomyolysis associated with Rosuvastatin rosuvastatin in post-marketing use is higher at the 40 mg dose.

Rosuvastatin must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination (see section 4.5). The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness.

Statin therapy may be re-introduced seven days after the last dose of fusidic acid.

In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment of severe infections, the need for co-administration of rosuvastatin and fusidic acid should only be considered on a case by case basis and under close medical supervision.

Whilst on Treatment

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. 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 ?5x ULN). If symptoms resolve and CK levels return to normal, then consideration should be given to re-introducing Rosuvastatin Mylan 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.

There have been very rare reports of an immune-mediated necrotising myopathy (IMNM) during or after treatment with statins, including rosuvastatin. IMNM is clinically characterized characterised by proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment.

In clinical trials there was no evidence of increased skeletal muscle effects in the small number of patients dosed with Rosuvastatin 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, ciclosporin, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when given concomitantly with some HMG-CoA reductase inhibitors. Therefore, the combination of Rosuvastatin Mylan and gemfibrozil is not recommended. The benefit of further alterations in lipid levels by the combined use of Rosuvastatin Mylan 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 (see sections 4.5 and 4.8).

Combination of rosuvastatin and fusidic acid is not recommended. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination (see section 4.5).
Rosuvastatin Mylan must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination (see section 4.5). The patientPatients should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness.

Statin therapy may be re-introduced seven days after the last dose of fusidic acid.

In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment of severe infections, the need for co-administration of rRosuvastatin Mylan and fusidic acid should only be considered on a case by case basis and under close medical supervision.

Rosuvastatin Mylan 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).
Protease inhibitors
Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. Consideration should be given both to the benefit of lipid lowering by use of rosuvastatin in HIV patients receiving protease inhibitors and the potential for increased rosuvastatin plasma concentrations when initiating and up titrating rosuvastatin doses in patients treated with protease inhibitors. The concomitant use with certain protease inhibitors is not recommended unless the dose of rosuvastatin is adjusted (see sections 4.2 and 4.5).

4.5 Interaction with other medicinal products and other forms of interaction

Effect of co-administered medicinal products on rosuvastatin
Transporter protein inhibitors: Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter OATP1B1 and efflux transporter BCRP. Concomitant administration of rosuvastatin with medicinal products that are inhibitors of these transporter proteins may result in increased rosuvastatin plasma concentrations and an increased risk of myopathy (see sections 4.2, 4.4, and 4.5 Table 1).

Ciclosporin: During concomitant treatment with Rosuvastatin rosuvastatin and ciclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers (see Table 1). Rosuvastatin Mylan is contraindicated in patients receiving concomitant ciclosporin (see section 4.3). Concomitant administration did not affect plasma concentrations of ciclosporin.

Protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant protease inhibitor use may strongly increase rosuvastatin exposure (see Table 1). For instance, in a pharmacokinetic study, co-administration of 10 mg rosuvastatin and a combination product of two protease inhibitors (300 mg atazanavir / 100 mg ritonavir) in healthy volunteers was associated with an approximately three-fold and seven-fold increase in rosuvastatin steady-state AUC and Cmax respectively. The concomitant use of rosuvastatin and some protease inhibitor combinations may be considered after careful consideration of rosuvastatin dose adjustments based on the expected increase in rosuvastatin exposure (see sections 4.2, 4.4, and 4.5 Table 1).

Gemfibrozil and other lipid-lowering products: Concomitant use of rosuvastatin and gemfibrozil resulted in a 2-fold increase in rosuvastatin Cmax and AUC (see section 4.4).

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 1g/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 (see sections 4.3 and 4.4). These patients should also start with the 5 mg dose.

Ezetimibe: Concomitant use of 10 mg of Rosuvastatin rosuvastatin and 10 mg ezetimibe resulted in a 1.2 fold increase in AUC of rosuvastatin in hypercholesterolaemic subjects (Table 1). A pharmacodynamic interaction, in terms of adverse effects, between Rosuvastatin rosuvastatin and ezetimibe cannot be ruled out (see section 4.4).

Antacid: The simultaneous dosing of Rosuvastatin rosuvastatin with an antacid suspension containing aluminium 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 Rosuvastatinrosuvastatin. The clinical relevance of this interaction has not been studied.

Erythromycin: Concomitant use of Rosuvastatin rosuvastatin and erythromycin resulted in a 20% decrease in AUC(0-t) and a 30% decrease in Cmax of rosuvastatin. This interaction may be caused by the increase in gut motility caused by erythromycin.

Cytochrome P450 enzymes: Results from in vitro and in vivo studies show that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a poor substrate for these isoenzymes. Therefore, drug interactions resulting from cytochrome P450-mediated metabolism are not expected. No clinically relevant interactions have been observed between rosuvastatin and either fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4).

Interactions requiring rosuvastatin dose adjustments (see also Table 1):
When it is necessary to co-administer Rosuvastatin Mylan with other medicinal products known to increase exposure to rosuvastatin, doses of Rosuvastatin Mylan should be adjusted. Start with a 5 mg once daily dose of Rosuvastatin Mylan if the expected increase in exposure (AUC) is approximately 2-fold or higher. The maximum daily dose of Rosuvastatin Mylan should be adjusted so that the expected rosuvastatin exposure would not likely exceed that of a 40 mg daily dose of Rosuvastatin Mylan taken without interacting medicinal products, for example a 20 mg dose of Rosuvastatin Mylan with gemfibrozil (1.9-fold increase), and a 10 mg dose of Rosuvastatin Mylan with combination ritonavir/atazanavir/ritonavir (3.1-fold increase).

Fusidic acid:   Interaction studies with rosuvastatin and fusidic acid have not been conducted. The risk of myopathy including rhabdomyolysis may be increased by the concomitant administration of systemic fusidic acid with statins. The mechanism of this interaction (whether it is pharmacodynamic or pharmacokinetic, or both) is yet unknown. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination.

If treatment with systemic fusidic acid is necessary, rosuvastatin treatment should be discontinued throughout the duration of the fusidic acid treatment (see section 4.4).

4.8 Undesirable effects

The adverse events seen with rosuvastatin are generally mild and transient. In controlled clinical trials, less than 4% of rosuvastatin-treated patients were withdrawn due to adverse reactions.

Tabulated list of adverse reactions
Based on data from clinical studies and extensive post-marketing experience, the following table presents the adverse reaction profile for rosuvastatin. Adverse reactions listed below are classified according to frequency and system organ class (SOC).

The frequencies of adverse reactions are ranked according to the following convention: Common (=1/100 to <1/10); Uncommon (=1/1,000 to <1/100); Rare (=1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).

Renal effects:
Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with Rosuvastatinrosuvastatin. Shifts in urine protein from none or trace to ++ or
more were seen in <1% of patients at some time during treatment with 10 and 20 mg, and in approximately 3% of patients treated 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. Review of data from clinical trials and post-marketing experience to date has not identified a causal association between proteinuria and acute or progressive renal disease.

Haematuria has been observed in patients treated with Rosuvastatin rosuvastatin and clinical trial data show that the occurrence is low.

Skeletal muscle effects:
Effects on skeletal muscle e.g. myalgia, myopathy (including myositis) and, rarely, rhabdomyolysis with and without acute renal failure have been reported in Rosuvastatin rosuvastatin-treated patients with all doses and in particular with doses > 20 mg.

5.1  Pharmacodynamic properties

Clinical efficacy and safety
Rosuvastatin is effective in adults with hypercholesterolaemia, with and without hypertriglyceridaemia, regardless of race, sex, or age and in special populations such as diabetics, or patients with familial hypercholesterolaemia.

From pooled phase III data, rosuvastatin has been shown to be effective at treating the majority of patients with type IIa and IIb hypercholesterolaemia (mean baseline LDL-C about 4.8 mmol/l) to recognised European Atherosclerosis Society (EAS; 1998) guideline targets; about 80% of patients treated with 10 mg reached the EAS targets for LDL-C levels (<3 mmol/l).

In a large study, 435 patients with heterozygous familial hypercholesterolaemia were given rosuvastatin from 20 mg to 80 mg in a force-titration design. All doses showed a beneficial effect on lipid parameters and treatment to target goals. Following titration to a daily dose of 40 mg (12 weeks of treatment), LDL-C was reduced by 53%. Thirty-three percent (33%) of patients reached EAS guidelines for LDL-C levels (<3 mmol/l).

In a force-titration, open label trial, 42 patients (including 8 paediatric patients) with homozygous familial hypercholesterolaemia were evaluated for their response to rosuvastatin 20 - 40 mg. In the overall population, the mean LDL-C reduction was 22%.

Rosuvastatin was studied in a randomised, double-blind, placebo-controlled, multicenter, cross-over study with 20 mg once daily versus placebo in 14 children and adolescents (aged from 6 to 17 years) with homozygous familial hypercholesterolaemia. The study included an active 4-week dietary lead-in phase during which patients were treated with rosuvastatin 10 mg, a cross-over phase that consisted of a 6-week treatment period with rosuvastatin 20 mg preceded or followed by a 6-week placebo treatment period and a 12-week maintenance phase during which all patients were treated with rosuvastatin 20 mg. Patients who entered the study on ezetimibe or apheresis therapy continued the treatment throughout the entire study.

A statistically significant (p=0.005) reduction in LDL-C (22.3%, 85.4 mg/dL or 2.2 mmol/L) was observed following 6 weeks of treatment with rosuvastatin 20 mg versus placebo. Statistically significant reductions in Total-C (20.1%, p=0.003), nonHDL-C (22.9%, p=0.003) and ApoB (17.1%, p=0.024) were observed. Reductions were also seen in TG, LDL-C/HDL-C, Total-C/HDL-C, nonHDL-C/HDL-C and ApoB/ApoA-1 following 6 weeks of treatment with rosuvastatin 20 mg versus placebo. The reduction in LDL-C after 6 weeks of treatment with rosuvastatin 20 mg following 6 weeks of treatment with placebo was maintained over 12 weeks of continuous therapy.

In the 7 evaluable children and adolescent patients (aged from 8 to 17 years) from the force-titration open label study with homozygous familial hypercholesterolaemia (see above), the percent reduction in LDL-C (21.0%), Total-C (19.2%), and non-HDL-C (21.0%) from baseline following 6 weeks of treatment with rosuvastatin 20 mg was consistent with that observed in the aforementioned study in children and adolescents with homozygous familial hypercholesterolaemia.

Special populations:

Age and sex: There was no clinically relevant effect of age or sex on the pharmacokinetics of rosuvastatin in adults. The exposure pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolaemia appears to be was similar to or lower than that in of adult patients with dyslipidaemia volunteers (see “‘Paediatric population’” below).

 

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core
Cellulose, mMicrocrystalline cellulose
Lactose monohydrate
Silica, colloidal anhydrous
Crospovidone
Magnesium oxide
Magnesium stearate
Iron oxide red (E172)

Film-coating
5 mg tablet:
Lactose monohydrate
Hypromellose
Titanium dioxide (E171)
Triacetin
Sunset Yellow FCF (E110) – 10mg, 20mg & 40mg only
Quinoline yellow (E104) – 5mg only
Allura red (E129)
Indigo carmine (E132)

10 mg, 20 mg or 40 mg tablet:
Lactose monohydrate
Hypromellose
Titanium dioxide (E171)
Triacetin

Sunset Yyellow FCF (E110) – 10mg, 20mg & 40mg only
Allura red (E129)
Indigo carmine (E132)

6.5 Nature and contents of container

Polyamide / aluminium / LDPE desiccant – HDPE and aluminium foil blister
OPA / aluminium / PVC - aluminium blisters
PVC / Aclar - aluminium blisters
Pack sizes: 14, 15, 28, 30, 60, 56, 60, 84, 90 and 98 film-coated tablets.

HDPE bottle with a desiccant.
Pack sizes: 28, 30, 56, 60, 84 and 90 film-coated tablets.

Not all pack sizes may be marketed.

 

 

Updated on 13 February 2018 PIL

Reasons for updating

  • New PIL for new product

Updated on 13 February 2018 PIL

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - excipient warnings
  • Change to section 3 - use in children/adolescents
  • Change to section 4 - possible side effects
  • Change to section 6 - what the product looks like and pack contents

Updated on 7 December 2016 SmPC

Reasons for updating

  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

6.5 Nature and contents of container

Polyamide / aluminium / LDPE desiccant – HDPE and hard tempered aluminium foil blister
OPA / aluminium / PVC - aluminium blisters
PVC / Aclar - aluminium blisters
in pPack sizes: of 14, 15, 28, 30, 60, 56, 84, 90 and 98 film-coated tablets.

HDPE bottle with a desiccant
polypropylene screw closure and silica gel and activated carbon in desiccant bag in pPack sizes: of 28, 30, 56, 60, 84 and 90 film-coated tablets.

Not all pack sizes may be marketed.

Updated on 27 September 2016 PIL

Reasons for updating

  • Change to further information section
  • Change to date of revision

Updated on 11 December 2015 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

4.4 Special warnings and precautions for use

 

Skeletal Muscle Effects

 

 

Effects on skeletal muscle e.g. myalgia, myopathy and, rarely, rhabdomyolysis have been reported in Rosuvastatin -treated patients with all doses and in particular with doses > 20 mg. Very rare cases of rhabdomyolysis have been reported with the use of ezetimibe in combination with HMG-CoA reductase inhibitors. A pharmacodynamic interaction cannot be excluded (see section 4.5) and caution should be exercised with their combined use.

 

As with other HMG-CoA reductase inhibitors, the reporting rate for rhabdomyolysis associated with Rosuvastatin in post-marketing use is higher at the 40 mg dose.

 

 

Rosuvastatin must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination (see section 4.5). The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness.

 

Statin therapy may be re-introduced seven days after the last dose of fusidic acid.

In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment of severe infections, the need for co-administration of rosuvastatin and fusidic acid should only be considered on a case by case basis and under close medical supervision.

 

 

 

 

4.5 Interaction with other medicinal products and other forms of interaction

 

Eltrombopag 75 mg OD,

105 days

10 mg, single dose

 

1.6-fold


 

Fusidic acid

:

 

 

 

 

 

Interaction studies with rosuvastatin and fusidic acid have not been conducted. As with other statins, muscle-related events, including rhabdomyolysis, have been reported in post-marketing experience with rosuvastatin and fusidic acid given concurrently.

Therefore, the combination of rosuvastatin and fusidic acid is not recommended. If possible, temporary suspension of rosuvastatin treatment is recommended. If unavoidable, patients should be closely monitored. Rosuvastatin must not be co-administered with fusidic acid. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment. The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness.

Statin therapy may be re-introduced seven days after the last dose of fusidic acid. In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment of severe infections, the need for co-administration of rosuvastatin and fusidic acid should only be considered on a case by case basis and under close medical supervision

 

 

The risk of myopathy including rhabdomyolysis may be increased by the concomitant administration of systemic fusidic acid with statins. The mechanism of this interaction (whether it is pharmacodynamic or pharmacokinetic, or both) is yet unknown. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination.

 

If treatment with systemic fusidic acid is necessary, rosuvastatin treatment should be discontinued throughout the duration of the fusidic acid treatment (see section 4.4).

 



 

10. DATE OF REVISION OF THE TEXT

 

 

July 2015

 

 

December 2015

 

 

 

 









Updated on 10 December 2015 PIL

Reasons for updating

  • Change of trade or active ingredient name
  • Change to warnings or special precautions for use
  • Change to drug interactions
  • Change to date of revision

Updated on 8 October 2015 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.1 - List of excipients

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4.4 Special warnings and precautions for use

 


Whilst on Treatment
Combination of rosuvastatin and fusidic acid is not recommended. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination (see section 4.5).

Excipients
Rosuvastatin Film-coated Tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficient of glucose-galactose malabsorption should not take this medicine.
This medical product also contains Allura red and Sunset yellow AC Aluminium Lake, which may cause allergic reactions.


4.5 Interaction with other medicinal products and other forms of interaction

Table 1. Effect of co-administered medicinal products on rosuvastatin exposure (AUC; in order of decreasing magnitude) from published clinical trials

Interacting drug dose regimen:    Simeprevir 150 mg OD, 7 days
Rosuvastatin dose regimen:         1 mg, single dose
Change in rosuvastatin AUC:     2.8-fold

Interacting drug dose regimen
:    Clopidogrel 300 mg loading, followed by 75 mg at 24 hours
Rosuvastatin dose regimen:         
20 mg, single dose
Change in rosuvastatin AUC:     2-fold

Interacting drug dose regimen:    Eltrombopag 75 mg OD, 10 5 days

Other medicinal products

Digoxin:
Based on data from specific interaction studies no clinically relevant interaction with digoxin is expected.

Fusidic acid
Interaction studies with rosuvastatin and fusidic acid have not been conducted. As with other statins, musclerelated events, including rhabdomyolysis, have been reported in post-marketing experience with rosuvastatin and fusidic acid given concurrently.
Therefore, the combination of rosuvastatin and fusidic acid is not recommended. If possible, temporary suspension of rosuvastatin treatment is recommended. If unavoidable, patients should be closely monitored.


4.8 Undesirable effects

Liver effects
:
The following adverse events have been reported with some statins:
Depression.
sexual dysfunction.


6.1 List of excipients

Tablet core
Cellulose, microcrystalline
Lactose monohydrate
Silica, colloidal anhydrous
Crospovidone
(Type A)
Magnesium oxide, light
Magnesium stearate
Iron oxide red (E172)

Film-coating
Lactose monohydrate
Hypromellose
Titanium dioxide (E171)
Triacetin
Sunset
yellow FCF Aluminium Lake (E110) – 10 mg, 20 mg & 40 mg only
Quinoline yellow
Aluminium Lake (E104) – 5 mg only
Allura
red AC Aluminium Lake (E129)
Indigo
carmine Aluminium Lake (E132)


(internal ref: SK/H/0133/IB/013 PR523541)

 

Updated on 8 October 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
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Updated on 10 September 2015 PIL

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  • Change to further information section
  • Change to date of revision

Updated on 29 August 2014 SmPC

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  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

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Changes from two variationns, too extensive to list as changes. Please see attached clean SPC

Updated on 15 August 2014 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions
  • Change to information about pregnancy or lactation
  • Change to date of revision
  • Change to dosage and administration
  • Change to product name
  • Addition of information on reporting a side effect.

Updated on 21 August 2012 SmPC

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  • New SPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

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None provided

Updated on 21 August 2012 PIL

Reasons for updating

  • New PIL for new product