Rosuvastatin

Registered South African indications:

• To reduce the risk of cardiovascular events
• Hypercholesterolaemia, as an adjunct to diet when response to diet and exercise is inadequate

Contraindications

Registered contraindications in South Africa & other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 times the upper limit of normal (ULN)
• Severe renal impairment (creatinine clearance <30ml/min)
• Patients with myopathy
• Concomitant use with the combination sofosbuvir/velpatasvir/voxilaprevir (Applicable to other jurisdictions only)
• Concomitant use with ciclosporin
• Pregnancy
• Lactation
• Women of childbearing potential not using appropriate contraceptive measures
• The 40mg dose is contraindicated in patients with predisposing factors for myopathy/rhabdomyolysis. Such factors include
  • Moderate renal impairment (creatinine clearance <60ml/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

Cautions

Recommendations in South Africa & other jurisdictions

• Moderate renal impairment (5mg, 10mg, 20mg)
• Severe hepatic impairment
• Elderly (Recommendations in other jurisdictions)
• Asian population
• Children
• Interstitial lung disease
• Diabetes mellitus
• Galactose intolerance
• Lapp-lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: fct, tab

South African registered indications and dosages

To reduce the risk of cardiovascular events in 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
- To reduce the risk of non-fatal stroke, non-fatal MI, and the need for arterial revascularisation
Hypercholesterolemia, as an adjunct to diet when response to diet and exercise is inadequate 
- Primary hypercholesterolaemia including heterozygous familial hypercholesterolaemia 
- Mixed dyslipidaemia
- Isolated hypertriglyceridemia including Fredrickson Type IIa, IIb, and IV and heterozygous familial and non-familial hypercholesterolaemia 
- Primary dysbetalipoproteinaemia (Fredrickson Type III hyperlipoproteinaemia)

• Oral (fct, tab): Initial: 5mg, once daily for statin naïve or those switched from another HMG CoA reductase inhibitor; Titrate as necessary after 2-4 weeks; Most patients are controlled on 10mg, daily

A 5mg starting dose is recommended for patients of Asian ancestry and for patients requiring a smaller reduction in LDL-C to achieve treatment target

- Severe hypercholesterolaemia (including heterozygous familial hypercholesterolaemia)

• Oral (fct, tab): Initial: 20mg, once daily may be considered; Titrate as necessary after 2-4 weeks; Titration to 40mg should be done under specialist supervision for patients with severe hypercholesterolaemia at high cardiovascular risk

- Total cholesterol and LDL-C reduction in patients with homozygous familial hypercholesterolaemia either alone or as an adjunct to diet and other lipid-lowering treatments, e.g., LDL apheresis

• Oral (fct, tab): Initial: 20mg, once daily is recommended; Titrate as necessary after 2-4 weeks

Rosuvastatin 40mg should only be considered in patients with severe hypercholesterolaemia and high cardiovascular risk who do not achieve their treatment goal on 20mg of rosuvastatin or alternative therapy and in whom routine follow-up will be performed

Specialist supervision is recommended when the 40mg dose is initiated

The choice of start dose should take into account the individual patient's cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions

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

Before treatment initiation, the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment

See additional prescribing points on ethnic differences

Paed. forms avail. in SA and covered in this monograph: fct, tab

South African registered indications and dosages

Heterozygous familial hypercholesterolaemia
- To reduce total cholesterol, LDL-C and Apo B

Younger than 10 years

• No information available

Between 10 -17 years

• Oral (fct, tab): 5-20mg, once daily; Titrate appropriately to achieve treatment goal; Safety and efficacy of doses >20mg have not been studied in this population 

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

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

Note: Some available Professional Information (PI) recommendations state paediatric use should only be carried out by specialists

Before treatment initiation, the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment

See additional prescribing points on ethnic differences

Pregnancy

Recommendations below are applicable to South Africa and other jurisdictions

• Contraindicated
• The safety of rosuvastatin during pregnancy has not been established 
• Women of childbearing potential should use appropriate contraceptive measures
• 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 
• Animal studies provide limited evidence of reproductive toxicity. If a patient becomes pregnant during use of this product, treatment should be discontinued immediately 

Breastfeeding

South African recommendations

• Contraindicated
• The safety of rosuvastatin during breastfeeding has not been established 
• Rosuvastatin is excreted in the milk of rats. There is no data available with respect to excretion of rosuvastatin in milk in humans

Recommendations in other jurisdictions

• Contraindicated
• Rosuvastatin is excreted in the milk of rats. There are no data with respect to excretion in milk in humans

Recommendations below are applicable to South Africa and other jurisdictions

• Mild: No dose adjustment recommended
• Moderate: Caution; dose adjustment recommended (5mg, 10mg, 20mg tab)
  The recommended start dose is 5mg in patients with moderate renal impairment (CrCl<60ml/min)
• Moderate: Contraindicated (40mg)
• Severe: Contraindicated

South African recommendations

• Mild to moderate: No dose adjustment recommended
  There was no increase in systemic exposure to rosuvastatin in subjects with Child-Pugh scores of 7 or below. The usual starting dose applies in patients with mild to moderate hepatic impairment
• Severe: Caution; dose adjustment recommended
  Increased systemic exposure has been observed in subjects with Child-Pugh scores of 8 and 9
  In these patients an assessment of renal function should be considered. There is no experience in subjects with Child-Pugh scores above 9
  Patients with severe hepatic impairment should start therapy with rosuvastatin 5mg
  Increased systemic exposure to rosuvastatin has been observed in these patients, therefore the use of doses above rosuvastatin 10mg should be carefully considered 
• Active liver disease: Contraindicated

Recommendations in other jurisdictions

• Child-Pugh score ≤7: No dose adjustment recommended
  There was no increase in systemic exposure to rosuvastatin in subjects with Child-Pugh scores of 7 or below
• Child-Pugh scores of 8 and 9: Caution; no dose adjustment recommended
  Increased systemic exposure has been observed in subjects with Child-Pugh scores of 8 and 9
  In these patients an assessment of renal function should be considered
• Child-Pugh score >9: Caution; no information available
  There is no experience in subjects with Child-Pugh scores above 9
• Active liver disease: Contraindicated

South African recommendations

• No dose adjustment recommended
  The usual dose range applies

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  Start dose of 5mg is recommended in patients >70 years
  No other dose adjustment is necessary in relation to age

Central Nervous System Disorders

• Depression
• Headache
• Dizziness
• Polyneuropathy
• Memory loss
• Peripheral neuropathy
• Sleep disturbance
• Asthenia

Respiratory Disorders

• Cough
• Dyspnoea

Gastrointestinal Disorders

• Constipation
• Nausea
• Abdominal pain
• Pancreatitis
• Diarrhoea

Hepatobiliary Disorders

• Increased hepatic transaminases
• Jaundice
• Hepatitis

Genitourinary Disorders

• Haematuria
• Gynaecomastia

Endocrine and Metabolic Disorders

• Diabetes mellitus

Musculoskeletal Disorders

• Myalgia
• Myopathy
• Rhabdomyolysis
• Arthralgia
• Tendon disorders, sometimes complicated by rupture
• Immune-mediated necrotising myopathy

Skin and Subcutaneous Tissue Disorders

• Pruritis
• Rash
• Urticaria
• Stevens-Johnson syndrome
• Oedema

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Angioedema
• Thrombocytopenia

• OATP1B1 inhibitors
• Ciclosporin
• Fibrates
• Sofosbuvir/velpatasvir/voxilaprevir
• Protease inhibitors
• Other lipid-modifying agents
• Ezetimibe
• Antacids
• Erythromycin
• Warfarin
• Oral contraceptive
• Hormone replacement therapy
• Digoxin
• Fusidic acid

• Hepatic function

Specific cases may require

• Creatine phosphokinase (CK)
• Blood glucose

Ethnic differences

• A 5mg starting dose of rosuvastatin should be considered for Asian patients. Increased plasma concentration of rosuvastatin is seen in Asian subjects. The increased systemic exposure should be taken into consideration when treating Asian patients whose hypercholesterolaemia is not adequately controlled at doses up to 20mg daily

Rosuvstatin is a selective, competitive inhibitor of HMG CoA reductase, the enzyme which is responsible for converting HMG CoA to mevalonate, a precursor for sterols.  Decreased hepatic cholesterol levels stimulates upregulation of hepatic low-density lipoprotein-C (LDL-C) receptors which increases hepatic uptake of LDL-C and reduces serum LDL-C concentrations. 

Tablet 5mg 

• Cresagen fct (Trinity)
• Crestor (AstraZeneca) originator
• Rostor (Mylan)
• Rosuvastatin 5 Adco (Adcock Ingram)
• Rosuvastatin 5 PharmC (Pharmacorp)
• Rosuvastatin (Sandoz)
• Rosvator 5 (Ranbaxy Pharmaceuticals)
• Rubistor 5mg (Ruby Pharmaceuticals)
• Torolar 5 (Trinity Pharma)
• Trinchol 5 (Trinity Pharma)
• Vusor 5 (Teva Pharmaceuticals)
• Xartigen 5mg (Accord Healthcare)
• Zuvamor (Astrazeneca)

Tablet 10mg

• Cresagen fct (Trinity)
• Crestor (AstraZeneca) originator
• Rocrest (Austell)
• Rostor (Mylan)
• Rosuvastatin 10 Adco (Adcock Ingram)
• Rosuvastatin 10 PharmC (Pharmacorp)
• Rosuvastatin (Sandoz)
• Rosvator 10 (Ranbaxy Pharmaceuticals)
• Rubistor 10mg (Ruby Pharmaceuticals)
• Storwin (Zentiva)
• Torolar 10 (Trinity Pharma)
• Trinchol 10 (Trinity Pharma)
• Vusor 10 (Teva Pharmaceuticals)
• Xartigen 10mg (Accord Healthcare)
• Zuvamor (Astrazeneca)

Film-coated tablet 15mg

• Crevas 15mg (Pharma Dynamics)

Tablet 20mg 

• Cresagen fct (Trinity)
• Crestor (AstraZeneca) originator
• Rocrest (Austell)
• Rostor (Mylan)
• Rosuvastatin (Sandoz)
• Rosuvastatin 20 Adco (Adcock Ingram)
• Rosuvastatin 20 PharmC (Pharmacorp)
• Rosvator 20 (Ranbaxy Pharmaceuticals)
• Rubistor 20mg (Ruby Pharmaceuticals)
• Storwin (Zentiva)
• Torolar 20 (Trinity Pharma)
• Trinchol 20 (Trinity Pharma)
• Vusor 10 (Teva Pharmaceuticals)
• Xartigen 20mg (Accord Healthcare)
• Zuvamor (AstraZeneca)

Film-coated tablet 30mg

• Crevas 30mg (Pharma Dynamics)

Tablet 40mg

• Cresagen fct (Trinity)
• Crestor (AstraZeneca) originator
• Rocrest (Austell)
• Rostor (Mylan)
• Rosuvastatin (Sandoz)
• Rosuvastatin 40 Adco (Adcock Ingram)
• Rosuvastatin 40 PharmC (Pharmacorp)
• Rosvator 40 (Ranbaxy Pharmaceuticals)
• Rubistor 40mg (Ruby Pharmaceuticals)
• Storwin (Zentiva)
• Torolar 40 (Trinity Pharma)
• Trinchol 40 (Trinity Pharma)
• Vusor 40 (Teva Pharmaceuticals)
• Xartigen 40mg (Accord Healthcare)
• Zuvamor (AstraZeneca)