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).
Blood and lymphatic system disorders:
Immune system disorders:
Rare: hypersensitivity reactions including angioedema.
Common: diabetes mellitus (Frequency will depend on the presence or absence of risk factors (fasting blood glucose ≥5.6 mmol/L, BMI >30 kg/m2
, raised triglycerides, history of hypertension)).
Not known: depression.
Nervous system disorders:
Common: headache, dizziness.
Very rare: polyneuropathy, memory loss.
Not known: peripheral neuropathy, sleep disturbances (including insomnia and nightmares).
Respiratory, thoracic and mediastinal disorders:
Not known: cough, dyspnea.
Common: constipation, nausea, abdominal pain.
Not known: diarrhoea.
Rare: increased hepatic transaminases.
Very rare: jaundice, hepatitis.
Skin and subcutaneous tissue disorders:
Uncommon: pruritis, rash, urticaria.
Not known: Stevens-Johnson syndrome.
Musculoskeletal and connective tissue disorders:
Rare: myopathy (including myositis), rhabdomyolysis, lupus-like syndrome, muscle rupture.
Very rare: arthralgia.
Not known: Tendon disorders, sometimes complicated by rupture, immune-mediated necrotizing myopathy.
Renal and urinary disorders:
Very rare: haematuria.
Reproductive system and breast disorders:
Very rare: gynaecomastia.
General disorders and administration site conditions:
Not known: oedema.
As with other HMG-CoA reductase inhibitors, the incidence of adverse drug reactions tends to be dose dependent.
Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with rosuvastatin. 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 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-treated patients with all doses and in particular with doses >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 (>5x ULN), treatment should be discontinued.
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.
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.
Creatine kinase elevations >10x ULN and muscle symptoms following exercise or increased physical activity were observed more frequently in a 52-week clinical trial of children and adolescents compared to adults. In other respects, the safety profile of rosuvastatin was similar in children and adolescents compared to adults.
Clinical studies experience:
In JUPITER study, there was a significantly higher frequency of diabetes mellitus reported in patients taking rosuvastatin (2.8%) versus patients taking placebo (2.3%). Mean HbA1c was significantly increased by 0.1% in rosuvastatin-treated patients compared to placebo-treated patients. The number of patients with a HbA1c >6.5% at the end of the trial was significantly higher in rosuvastatin-treated versus placebo-treated patients.
There have been rare post-marketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).