Rosuvastatin Unicorn 5/10/20/40 5mg/10mg/20mg/40mg FC tablets

To reduce the risk of cardiovascular events: In adult patients with an increased risk of atherosclerotic cardiovascular disease based on the presence of cardiovascular disease risk markers such as an elevated high-sensitivity C-reactive protein (hsCRP) level, age, hypertension, low HDL-C, smoking or a family history of premature coronary heart disease, ROSUVASTATIN UNICORN is indicated to reduce the risk of non-fatal stroke, non-fatal MI and the need for arterial revascularisation.

In adult patients with hypercholesterolaemia:

• ROSUVASTATIN UNICORN is indicated for patients with primary hypercholesterolaemia, mixed dyslipidaemia and isolated hypertriglyceridaemia (including Fredrickson Type IIa, IIb and IV; and heterozygous familial and non-familial hypercholesterolaemia) as an adjunct to diet when response to diet and exercise is inadequate.
• ROSUVASTATIN UNICORN is indicated to treat patients with primary dysbetalipoproteinaemia (Fredrickson Type III hyperlipoproteinaemia).
• ROSUVASTATIN UNICORN is also indicated to reduce Total Cholesterol and LDL-C in patients with homozygous familial hypercholesterolaemia, either alone or as an adjunct to diet and other lipid lowering treatments (e.g. LDL apheresis).

ROSUVASTATIN UNICORN 40 mg should only be considered in patients with severe hypercholesterolaemia and high cardiovascular risk who do not achieve their treatment goal on 20 mg of ROSUVASTATIN UNICORN or alternative therapy. Specialist supervision is recommended when the 40 mg dose is initiated (see section 4.4).

Children and adolescents 10 to 17 years of age: ROSUVASTATIN UNICORN is indicated to reduce the Total Cholesterol, LDL-C and Apo B in patients with heterozygous familial hypercholesterolaemia (HeFH).

Before treatment initiation, the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment. The dose range for ROSUVASTATIN UNICORN is 5 to 40 mg orally once a day. The recommended start dose is 5 mg once a day. The dosage of ROSUVASTATIN UNICORN should be individualised according to the goal of therapy and patient response. The majority of patients are controlled at the 10 mg dose. However, if necessary, dose adjustment can be made at 2 to 4 week intervals (see section 5.1). ROSUVASTATIN UNICORN may be given at any time of the day, with or without food.

Adults: Primary hypercholesterolaemia (including heterozygous familial hypercholesterolaemia), mixed dyslipidaemia, dysbetalipoproteinaemia (Fredrickson Type III hyperlipoproteinaemia) and isolated hypertriglyceridaemia:

The recommended start dose is 5 mg once a day. A 5 mg starting dose is recommended for patients of Asian ancestry, and for patients requiring a smaller reduction in LDL-C to achieve treatment target. For patients with severe hypercholesterolaemia (including heterozygous familial hypercholesterolaemia), a start dose of 20 mg may be considered.

Homozygous familial hypercholesterolaemia: For patients with homozygous familial hypercholesterolaemia a start dose of 20 mg once a day is recommended.

Children and adolescents 10 to 17 years of age: In children and adolescents with heterozygous familial hypercholesterolaemia the usual dose range is 5 to 20 mg orally once daily. The dose should be appropriately titrated to achieve treatment goal. Safety and efficacy of doses greater than 20 mg have not been studied in this population.

In children and adolescents with homozygous familial hypercholesterolaemia experience is limited to a small number of patients (aged 8 years and above).

Special populations: Use in the elderly: The usual dose range applies. Dosage in patients with renal insufficiency: The starting dose applies in patients with mild to moderate renal impairment. For patients with severe renal impairment the dose of ROSUVASTATIN UNICORN should not exceed 10 mg once daily. Dosage in patients with hepatic insufficiency: The usual starting dose applies in patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment should start therapy with ROSUVASTATIN UNICORN 5 mg. Increased systemic exposure to rosuvastatin has been observed in these patients, therefore the use of doses above ROSUVASTATIN UNICORN 10 mg should be carefully considered (see section 5.2).

Race: A 5 mg starting dose of ROSUVASTATIN UNICORN should be considered for Asian patients. Increased plasma concentration of rosuvastatin has been seen in Asian subjects (see sections 4.4 and 5.2). The increased systemic exposure should be taken into consideration when treating Asian patients whose hypercholesterolaemia is not adequately controlled at doses up to 20 mg daily.

Concomitant therapy: ROSUVASTATIN UNICORN has been shown to have additive efficacy in lowering triglycerides when used in combination with fenofibrate and in increasing HDL-C levels when used in combination with niacin. ROSUVASTATIN UNICORN can also be used in combination with ezetimibe or bile acid sequestrants (see section 4.4).

Interactions requiring dose adjustments: Ciclosporin: Increased systemic exposure to rosuvastatin has been observed in patients taking concomitant ROSUVASTATIN UNICORN and Ciclosporin. For the ROSUVASTATIN UNICORN dose range (10 to 40 mg) this combination is not recommended (see section 4.3). Gemfibrozil: Increased systemic exposure to rosuvastatin has been observed in subjects taking concomitant ROSUVASTATIN UNICORN and gemfibrozil. Patients taking this combination should start therapy with ROSUVASTATIN UNICORN 5 mg once daily and should not exceed a dose of ROSUVASTATIN UNICORN 20 mg once daily (see section 4.5).

ROSUVASTATIN UNICORN is contraindicated in:

• Patients with hypersensitivity to rosuvastatin or to any of the excipients of ROSUVASTATIN UNICORN
• Patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x the upper limit of normal (ULN)
• Patients with severe renal impairment (creatinine clearance <30 ml/min)
• Patients with myopathy
• Patients receiving concomitant ciclosporin
• Patients receiving concomitant combination of sofosbuvir / velpatasvir / voxilaprevir (see section 4.5)
• Pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures

The 40 mg dose is contraindicated in patients with predisposing factors for myopathy / rhabdomyolysis. Such factors include:

• Moderate renal impairment (creatinine clearance < 60 ml/min)
• Hypothyroidism
• Personal or family history of hereditary muscular disorders
• Previous history of muscular toxicity with another HMG - CoA reductase inhibitor or fibrate
• Alcohol abuse
• Situations where an increase in plasma levels may occur
• Asian patients
• Concomitant use of fibrates (See sections 4.4, 4.5 and 5.2)

Safety in pregnancy and lactation has not been established.

Renal Effects: Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of ROSUVASTATIN UNICORN 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 patients treated with rosuvastatin at 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.

Patients who develop any signs or symptoms suggestive of myopathy should have their creatine kinase (CK) levels measured. ROSUVASTATIN UNICORN therapy should be discontinued if myopathy is diagnosed or suspected.

Creatine Kinase Measurement: Creatine kinase (CK) should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase, which may confound interpretation of the result. If CK levels are significantly elevated at baseline (> 5xULN) a confirmatory test should be carried out within 5 to 7 days. If the repeat test confirms a baseline CK > 5xULN, treatment should not be started.

Before Treatment: ROSUVASTATIN UNICORN should be prescribed with caution in patients with predisposing factors for myopathy/rhabdomyolysis. Such factors include:

• renal impairment
• hypothyroidism
• personal or family history of hereditary muscular disorders
• previous history of muscular toxicity with another HMG - CoA reductase inhibitor or fibrate
• alcohol abuse
• age > 70 years
• situations where an increase in plasma levels may occur (see sections 4.2, 4.5 and 5.2)
• concomitant use of fibrates.

In such patients the risk of treatment should be considered in relation to possible benefit and clinical monitoring is recommended. If CK levels are significantly elevated at baseline (> 5xULN) treatment should not be started.

Whilst on Treatment: Patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever. 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 u2264 5xULN). If symptoms resolve and CK levels return to normal, then consideration should be given to re-introducing ROSUVASTATIN UNICORN 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 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 UNICORN and concomitant therapy. However, an increase in the incidence of myositis and myopathy has been seen in patients receiving HMG - CoA reductase inhibitors such as ROSUVASTATIN UNICORN together with ciclosporin, fibric acid derivatives, including gemfibrozil, 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 UNICORN and gemfibrozil is not recommended. The benefit of further alterations in lipid levels by the combined use of ROSUVASTATIN UNICORN 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 4.3, 4.5 and 4.8).

ROSUVASTATIN UNICORN 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 this combination (see section 4.5). Patients 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 UNICORN and fusidic acid should only be considered on a case by case basis and under close medical supervision.

ROSUVASTATIN UNICORN 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).

Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which could be life-threatening or fatal, have been reported with rosuvastatin (see section 4.8). At the time of prescription, patients should be advised of the signs and symptoms of severe skin reactions and be closely monitored. If signs and symptoms suggestive of this reaction appear, ROSUVASTATIN UNICORN should be discontinued immediately, and an alternative treatment should be considered. If the patient has developed a serious reaction such as SJS or DRESS with the use of ROSUVASTATIN UNICORN, treatment with ROSUVASTATIN UNICORN must not be restarted in this patient at any time.

Liver Effects: ROSUVASTATIN UNICORN should be used with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease. It is recommended that liver function tests be carried out prior to, and 3 months following the initiation of treatment. ROSUVASTATIN UNICORN should be discontinued, or the dose reduced if the level of serum transaminases is greater than 3 times the upper limit of normal. The reporting rate for serious hepatic events (consisting mainly of increased hepatic transaminases) in post-marketing use is higher at the 40 mg dose. In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to initiating therapy with ROSUVASTATIN UNICORN.

Race: Pharmacokinetic studies show an increase in exposure in Asian subjects compared with Caucasians (see sections 4.2, 4.3 and 5.2).

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 UNICORN in HIV patients receiving protease inhibitors and the potential for increased rosuvastatin plasma concentrations when initiating and up titrating ROSUVASTATIN UNICORN doses in patients treated with protease inhibitors. The concomitant use with certain protease inhibitors is not recommended unless the dose of ROSUVASTATIN UNICORN is adjusted (see sections 4.2 and 4.5).

Interstitial lung disease: Exceptional cases of interstitial lung disease have been reported with some statins, especially with long-term therapy (see section 4.8). Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.

Diabetes Mellitus: Some evidence suggests that statins as a class raise blood glucose and in some patients, at high risk of future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5,6 to 6,9 mmol/l, BMI > 30 kg/m2, raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.

In the JUPITER study, the reported overall frequency of diabetes mellitus was 2,8 % in rosuvastatin and 2,3 % in placebo, mostly in patients with fasting glucose 5,6 to 6,9 mmol/l.

Children and adolescents 10 to 17 years of age: The evaluation of linear growth (height), weight, BMI (body mass index), and secondary characteristics of sexual maturation by Tanner staging in paediatric patients 10 to 17 years taking rosuvastatin is limited to a 1 year period. After 52 weeks of study treatment, no effect on growth, weight, BMI or sexual maturation was detected (see section 5.2). In a clinical trial of children and adolescents receiving rosuvastatin for 52 weeks, CK elevations >10xULN and muscle symptoms following exercise or increased physical activity were observed more frequently compared to observations in clinical trials in adults (see section 4.8).

Lactose intolerance: ROSUVASTATIN UNICORN contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take ROSUVASTATIN UNICORN.

Effect of co-administered medicines 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 UNICORN with medicines 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: Co-administration of rosuvastatin with ciclosporin resulted in no significant changes in ciclosporin plasma concentration. However during concomitant treatment with ROSUVASTATIN UNICORN and ciclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers (see Table 1). ROSUVASTATIN UNICORN is contraindicated in patients receiving concomitant ciclosporin (see sections 4.2 and 4.3).

Protease inhibitors: Increased systemic exposure to rosuvastatin has been observed in subjects in pharmacokinetic studies receiving rosuvastatin with various protease inhibitors in combination with ritonavir (see Table 1). For instance, in a pharmacokinetic study, co-administration of 10mg 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 AUC and C max respectively. Adverse events attributed to rosuvastatin in these studies were consistent with the known safety profile of rosuvastatin. The concomitant use of ROSUVASTATIN UNICORN and some protease inhibitor combinations may be considered after careful consideration of ROSUVASTATIN UNICORN dose adjustments based on the expected increase in rosuvastatin exposure. The lowest dose of ROSUVASTATIN UNICORN that provides therapeutic benefit to the patient should be used, and close monitoring of adverse events is indicated. In HIV-infected patients receiving protease inhibitors the potential risks of this increased rosuvastatin plasma concentrations when initiating and up-titrating ROSUVASTATIN UNICORN doses in patients treated with protease inhibitors, as the combination, may lead to an increased incidence of adverse events (see sections 4.2, 4.4 and 4.5 Table 1).

Gemfibrozil and other lipid-lowering products: Concomitant use of rosuvastatin calcium and gemfibrozil resulted in a 2-fold increase in rosuvastatin C max and AUC (0-t) (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 1 g/day) of niacin (nicotinic acid) increase the risk of myopathy when given concomitantly with HMG - CoA reductase inhibitors, probably because they can produce myopathy when given alone. The 40 mg dose is contraindicated with concomitant use of a fibrate (see sections 4.3 and 4.4). These patients should also start with the 5mg dose.

Ezetimibe: Concomitant use of rosuvastatin 10 mg and ezetimibe 10 mg 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 UNICORN and ezetimibe cannot be ruled out (see section 4.4).

Antacids: The simultaneous dosing of 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 rosuvastatin. The clinical relevance of this interaction has not been studied.

Erythromycin: Concomitant use of ROSUVASTATIN UNICORN and erythromycin resulted in a 20 % decrease in AUC and a 30 % decrease in C max of rosuvastatin. This interaction may be caused by the increase in gut motility caused by erythromycin.

Cytochrome P450 enzymes: In vitro and in vivo data indicate that rosuvastatin has no clinically significant cytochrome P450 interactions (as a substrate, inhibitor or inducer). 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).

Ticagrelor: Ticagrelor can cause renal insufficiency and may affect renal excretion of rosuvastatin, increasing the risk for rosuvastatin accumulation. In some cases, co-administered ticagrelor and rosuvastatin led to renal function decrease, increased CPK level and rhabdomyolysis. Renal function and CPK control is recommended while using ticagrelor and rosuvastatin concomitantly.

Interactions requiring rosuvastatin dose adjustments (see also Table 1): When it is necessary to co-administer ROSUVASTATIN UNICORN with other medicines known to increase exposure to rosuvastatin, doses of ROSUVASTATIN UNICORN should be adjusted. Start with a 5 mg once daily dose of ROSUVASTATIN UNICORN if the expected increase in exposure (AUC) is approximately 2-fold or higher. The maximum daily dose of ROSUVASTATIN UNICORN should be adjusted so that the expected rosuvastatin exposure would not likely exceed that of a 40 mg daily dose of ROSUVASTATIN UNICORN taken without interacting medicines, for example a 20 mg dose of ROSUVASTATIN UNICORN with gemfibrozil (1,9-fold increase), and a 10 mg dose of ROSUVASTATIN UNICORN with combination ritonavir/atazanavir (3,1-fold increase).

If the medicine is observed to increase rosuvastatin AUC less than 2-fold, the starting dose need not be decreased but caution should be taken if increasing the ROSUVASTATIN UNICORN dose above 20 mg.

Table 1 Effect of co-administered medicines on rosuvastatin exposure (AUC; in order of decreasing magnitude) 2-fold or greater than 2-fold increase in AUC of rosuvastatin Interacting drug dose regimen Rosuvastatin dose regimen Change in rosuvastatin AUC* Sofosbuvir/velpatasvir/voxilaprevir (400 mg - 100 mg - 100 mg) + Voxilaprevir (100 mg) once daily for 15 days 10mg single dose 7,4-fold u2191 Ciclosporin 75 mg BID to 200 mg BID, 6 months 10 mg OD, 10 days 7,1-fold u2191 Darolutamide 600 mg BID, 5 days 5mg, single dose 5,2-fold u2191 Regorafenib 160 mg, OD, 14 days 5 mg, single dose 3,8-fold u2191 Atazanavir 300 mg/ritonavir 100 mg OD, 8 days 10 mg, single dose 3,1-fold u2191 Velpatasvir 100 mg OD 10 mg, single dose 2,7-fold u2191 Ombitasvir 25 mg/paritaprevir 150 mg/ Ritonavir 100 mg OD/ dasabuvir 400 mg BID, 14 days 5 mg, single dose 2,6-fold u2191 Grazoprevir 200 mg/elbasvir 50 mg OD, 11 days 10 mg, single dose 2,3-fold u2191 Glecaprevir 400 mg/pibrentasvir 120 mg OD, 7 days 5 mg OD, 7 days 2,2-fold u2191 Lopinavir 400 mg/ritonavir 100 mg BID, 17 days 20 mg OD, 7 days 2,1-fold u2191 Clopidogrel 300 mg loading, followed by 75 mg at 24 hours 20 mg, single dose 2-fold u2191 Gemfibrozil 600 mg BID, 7 days 80 mg, single dose 1,9-fold u2191 Less than 2-fold increase in AUC of rosuvastatin Interacting drug dose regimen Rosuvastatin dose regimen Change in rosuvastatin AUC * Eltrombopag 75 mg OD, 5 days 10 mg, single dose 1,6-fold u2191 Darunavir 600 mg/ritonavir 100 mg BID, 7 days 10 mg OD, 7 days 1,5-fold u2191 Tipranavir 500 mg/ritonavir 200 mg BID, 11 days 10 mg, single dose 1,4-fold u2191 Dronedarone 400 mg BID Not available 1,4-fold u2191 Itraconazole 200 mg OD, 5 days 10 mg, single dose **1,4-fold u2191 Ezetimibe 10 mg OD, 14 days 10 mg, OD, 14 days **1,2-fold u2191 Decrease in AUC of rosuvastatin Interacting drug dose regimen Rosuvastatin dose regimen Change in rosuvastatin AUC * Erythromycin 500 mg QID, 7 days 80 mg, single dose 20 % u2193 Baicalin 50 mg TID, 14 days 20 mg, single dose 47 % u2193 * Data given as x-fold change represent a simple ratio between co-administration and rosuvastatin alone. Data given as % change represent % difference relative to rosuvastatin alone. Increase is indicated as u201cu2191u201d, decrease as u201cu2193u201d. ** Several interaction studies have been performed at different rosuvastatin dosages, the table shows the most significant ratio AUC = area under curve; OD = once daily; BID = twice daily; TID = three times daily; QID = four times daily. The following medical product/combinations did not have a clinically significant effect on the AUC ratio of rosuvastatin at co-administration: Aleglitazar 0.3 mg 7 days dosing; Fenofibrate 67 mg 7 days TID dosing; Fluconazole 200mg 11 days OD dosing; Fosamprenavir 700 mg/ritonavir 100 mg 8 days BID dosing; Ketoconazole 200 mg 7 days BID dosing; Rifampin 450 mg 7 days OD dosing; Silymarin 140 mg 5 days TID dosing.

ROSUVASTATIN UNICORN is contraindicated in pregnancy and lactation (see section 4.3). Since cholesterol and other products of cholesterol biosynthesis are essential for the development of the foetus, the potential risk from inhibition of HMG - CoA reductase outweighs the advantage of treatment during pregnancy. If a patient becomes pregnant during use of this product, treatment should be discontinued immediately. The safety of ROSUVASTATIN UNICORN during pregnancy and whilst breastfeeding has not been established. Women of child-bearing potential should use appropriate contraceptive measures.

Pharmacology testing revealed no evidence of a sedative effect of ROSUVASTATIN UNICORN. From the safety profile, ROSUVASTATIN UNICORN is not expected to adversely affect the ability to drive or use machines. When driving vehicles or operating machines, it should be taken into account that dizziness may occur during treatment.

The adverse reactions seen with ROSUVASTATIN UNICORN 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.

System organ class Frequent Less frequent Frequency unknown Blood and the lymphatic system disorders Thrombocytopenia Immune system disorders Hypersensitivity reactions including angioedema Endocrine disorders Diabetes mellitus 1 Psychiatric disorders Depression Nervous system disorders Headache, dizziness Polyneuropathy, memory loss Peripheral neuropathy, Sleep disturbances (including insomnia and nightmares). Cardiac disorders Angina pectoris, chest pain, hypertension Vascular disorders Peripheral oedema Respiratory, thoracic and mediastinal disorders Dyspnoea, rhinitis, sinusitis, cough. Gastrointestinal disorders Diarrhoea, abdominal pain, constipation, vomiting, nausea Pancreatitis, gastritis, dyspepsia Hepato-biliary disorders Jaundice, hepatitis, increased hepatic transaminases Skin and subcutaneous tissue disorders Pruritus, rash, urticaria Stevens-Johnson syndrome, Drug reaction with eosinophilia and systemic symptoms (DRESS) Musculoskeletal, connective tissue and bone disorders Myalgia Myopathy (including myositis), rhabdomyolysis, which may occasionally be associated with impairment of renal function, has been reported with rosuvastatin lupus-like syndrome, muscle rupture, arthralgia Renal and urinary disorders Haematuria Proteinuria (see u201cInvestigationsu201d) Reproductive system and breast disorders Gynaecomastia General disorders and administration site conditions Asthenia Flu syndrome Oedema Investigations A dose-related increase in liver transaminases and creatine kinase (CK). Abnormal urinalysis testing (dipstick-positive proteinuria with haematuria). The protein detected was mostly tubular in origin.

1 Frequency will depend on the presence or absence of risk factors (fasting blood glucose u2265 5,6 mmol/l, BMI >30 kg/m2, raised triglycerides, history of hypertension).

As with other HMG - CoA reductase inhibitors, the incidence of adverse drug reactions tends to be dose dependent. Renal effects: Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with ROSUVASTATIN UNICORN. Shifts in urine protein from none or trace to ++ or more were seen in 20 mg. A dose-related increase in CK levels has been observed in patients taking rosuvastatin; the majority of cases were mild, asymptomatic and transient. If CK levels are elevated (>5xULN), treatment should be discontinued (see section 4.4). Liver effects: As with other HMG - CoA reductase inhibitors, a dose-related increase in transaminases has been observed in a small number of patients taking rosuvastatin; the majority of cases were mild, asymptomatic and transient. The following adverse events have been reported with some statins: Sexual dysfunction. Exceptional cases of interstitial lung disease, especially with long term therapy (see section 4.4). The reporting rates for rhabdomyolysis, serious renal events and serious hepatic events (consisting mainly of increased hepatic transaminases) is higher at the 40 mg dose. Children and adolescents 10 to 17 years of age: The safety profile of ROSUVASTATIN UNICORN is similar in children or adolescent patients and adults although CK elevations > 10xULN and muscle symptoms following exercise or increased physical activity were observed more frequently in a 52-week clinical trial of children and adolescents. However, the same special warnings and special precautions for use in adults also apply to children and adolescents (see section 4.4).

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8. Suspected adverse reactions can also be reported directly to the Holder of the Certificate of Registration (HCR) via [email protected].

Symptoms of overdosage: See section 4.8.

Treatment of overdosage: There is no specific treatment in the event of overdose. In the event of overdose, the patient should be treated symptomatically, and supportive measures instituted as required. Liver function and CK levels should be monitored. Haemodialysis is unlikely to be of benefit.