Adult: Dosage is individualised based on treatment goals, patient response and clinical practice guidelines. Initially, 5 or 10 mg once daily; may increase after 4 weeks if necessary. Usual Max: 20 mg once daily; a Max of 40 mg once daily may be used only in patients with severe hypercholesterolaemia at high CV risk who do not achieve the target cholesterol concentration at lower doses and who do not have risk factors for adverse effects. Patients with homozygous familial hypercholesterolaemia may be started on 20 mg once daily. Dosage may be increased at intervals of 2-4 weeks. Child: Heterozygous familial hypercholesterolaemia: Initially, 5 mg once daily. Usual dose range: 6-9 years 5-10 mg once daily; 10-17 years 5-20 mg once daily. Familial homozygous hypercholesterolaemia: 6-17 years Initially, 5 or 10 mg once daily, depending on age, weight and prior statin use, may titrate dose up to Max of 20 mg once daily according to individual response and tolerability, and depending on treatment recommendations. Elderly: >70 years Initially, 5 mg once daily.
Oral Prophylaxis of cardiovascular events in high-risk patients
Adult: 20 mg once daily. Elderly: >70 years Initially, 5 mg once daily.
Special Patient Group
Patients of Asian ancestry; those with predisposing factors to myopathy (e.g. hypothyroidism, personal or familial history of hereditary muscular disorders; alcohol abuse): Initially, 5 mg once daily. 40 mg dose is contraindicated.
Patients receiving concomitant therapy:
Ciclosporin: Avoid use. If use cannot be avoided, Max rosuvastatin dose is 5 mg once daily.
Gemfibrozil: Avoid use. If use cannot be avoided, initiate rosuvastatin at 5 mg once daily. Max: 10 mg once daily.
Atazanavir/ritonavir, lopinavir/ritonavir, or simeprevir: Initiate rosuvastatin at 5 mg once daily. Max: 10 mg once daily.
Pharmacogenomics:
The SLCO1B1 gene, which encodes the transporter protein OATP1B1, and the efflux transporter ABCG2, both play a role in the disposition of rosuvastatin and mediate the hepatic uptake of statins. Genetic polymorphism in SLCO1B1 or ABCG2 may affect the plasma concentrations of rosuvastatin.
rs4149056 (SLCO1B1)
Genotype
Considerations/Implications
CC, CT
Patients may have higher plasma concentrations of rosuvastatin but no change in LDL-cholesterol (LDL-C) levels has been noted. Other genetic and clinical factors may also influence the metabolism and response of the patient to rosuvastatin.
TT
Patients may have lower plasma concentrations of rosuvastatin but no change in LDL-C levels has been noted. Other genetic and clinical factors may also influence the metabolism and response of the patient to rosuvastatin.
rs2231142 (ABCG2)
Genotype
Considerations/Implications
GG
Patients who are treated with rosuvastatin 1) may have lower plasma concentrations of rosuvastatin 2) may have a reduced response to treatment as determined by a lower reduction in LDL-C. Other genetic and clinical factors may also influence a patient's response to rosuvastatin treatment and pharmacokinetics.
GT
Patients who are treated with rosuvastatin
1) may have lower
plasma concentrations of rosuvastatin 2) may have a reduced response to treatment as determined by a lower reduction in LDL-C, or
1) may have higher plasma concentrations of rosuvastatin 2) may have a better response to treatment as determined by a higher reduction in LDL-C.
Other genetic and clinical factors may also influence a patient's response to rosuvastatin treatment and pharmacokinetics.
TT
Patients who are treated with rosuvastatin 1) may have higher plasma concentrations of rosuvastatin 2) may have a better response to treatment as determined by a higher reduction in LDL-C. Other genetic and clinical factors may also influence a patient's response to rosuvastatin treatment and pharmacokinetics.
Renal Impairment
CrCl (mL/min)
Dosage
<30
Contraindicated.
30-60
Initially, 5 mg once daily (Max: 20 mg once daily).
Hepatic Impairment
Active liver disease: Contraindicated.
Administration
May be taken with or without food.
Contraindications
Active liver disease, including unexplained, persistent elevations of serum transaminases; myopathy. Severe renal impairment (CrCl <30 mL/min). Pregnancy and lactation.
Special Precautions
Patient with hypothyroidism; history of hereditary muscular disorders or muscular toxicity with another HMG-CoA reductase inhibitor or fibrates; excessive alcohol consumption, history of liver disease, severe respiratory failure. Patients of Asian ancestry, those with predisposing factors to myopathy or those taking concomitant ciclosporin, gemfibrozil, atazanavir/ritonavir, lopinavir/ritonavir, or simeprevir. Patient with SLCO1B1 and ABCG2 polymorphism. Moderate renal impairment (CrCl 30-60 mL/min). Children and elderly.
Adverse Reactions
Significant: Myopathy, myalgia, diabetes mellitus, haematuria, proteinuria, interstitial lung disease, liver enzyme abnormalities, increased creatine phosphokinase levels. Blood and lymphatic system disorders: Rarely, thrombocytopenia. Gastrointestinal disorders: Abdominal pain, constipation, nausea. General disorders and administration site conditions: Asthenia. Hepatobiliary disorders: Rarely, pancreatitis, hepatitis, jaundice. Immune system disorders: Hypersensitivity (e.g. angioedema). Musculoskeletal and connective tissue disorders: Rarely, arthralgia, muscle rupture, Lupus-like syndrome. Nervous system disorders: Dizziness, headache, peripheral neuropathy. Psychiatric disorders: Depression, sleep disorders (e.g. insomnia, nightmares). Reproductive system and breast disorders: Rarely, gynaecomastia. Skin and subcutaneous tissue disorders: Pruritus, rash, urticaria. Potentially Fatal: Rarely, rhabdomyolysis with acute renal failure secondary to myoglobinuria, hepatic failure.
Obtain lipid panel (HDL, LDL, total cholesterol, triglycerides) prior to therapy, then every 4-12 weeks after initial therapy and every 3-12 months thereafter; LFT prior to therapy and as needed thereafter; creatine phosphokinase when myopathy is considered or in high-risk patients.
Drug Interactions
Increased exposure with certain protease inhibitors (e.g. ritonavir-boosted regimens, simeprevir), gemfibrozil, ezetimibe, ciclosporin, colchicine. Decreased plasma concentration with Al- and Mg-containing antacids, erythromycin. May increase INR when given with vit K antagonists (e.g. warfarin). May increase the plasma concentration of oral contraceptives. May increase risk of myopathy with concurrent use of strong CYP3A4 inhibitors (e.g. clarithromycin, itraconazole), fenofibrate, nicotinic acid.
Action
Description: Rosuvastatin selectively and competitively inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. It increases the number of hepatic LDL receptors on the cell surface, thereby enhancing the uptake and catabolism of LDL. It also decreases apolipoprotein B, triglyceride and increases HDL concentrations. Onset: Within 1 week. Pharmacokinetics: Absorption: Incompletely absorbed from the gastrointestinal tract. Time to peak plasma concentration: 3-5 hours. Bioavailability: Approx 20%. Distribution: Enters breast milk. Volume of distribution: 134 L. Plasma protein binding: Approx 90%, mainly to albumin. Metabolism: Limited metabolism in the liver via CYP2C9 isoenzyme into N-desmethyl (approx 50% less active) and lactone metabolites (inactive). Excretion: Via faeces (approx 90%, mainly as unchanged drug); urine (approx 5%, as unchanged drug). Elimination half-life: Approx 19 hours.
Chemical Structure
Rosuvastatin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 446157, Rosuvastatin. https://pubchem.ncbi.nlm.nih.gov/compound/Rosuvastatin. Accessed July 29, 2020.
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