Adverse reactions : תופעות לוואי

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 In controlled clinical trials, less than 4% of Crestor-treated patients were withdrawn due to adverse events.

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 (>1/1000 to <1/100); Rare (>1/10,000 to <1/1000); Very rare (<1/10,000); Not known (cannot be estimated from the available data)

Table 2. Adverse reactions based on data from clinical studies and post-marketing experience 
System organ       Common          Uncommon        Rare                  Very rare        Not known class

Blood and                                          Thrombocytopenia lymphatic system disorders

Immune system                                      Hypersensitivity disorders                                          reactions including angioedema

Endocrine          Diabetes disorders          mellitus1

Psychiatric                                                                               Depression disorders

Nervous            Headache                                              Polyneuropathy Sleep system                                                                                  disturbances disorders          Dizziness                                             memory loss    (including insomnia and nightmares)
Peripheral neuropathy
Myasthenia gravis

Eye disorders                                                                             Ocular myasthenia
Respiratory,                                                                            Cough thoracic and mediastinal                                                                             Dyspnoea disorders

Gastro-            Constipation                  Pancreatitis                           Diarrhoea intestinal disorders          Nausea
Abdominal pain

Hepatobiliary                                    Increased hepatic    Jaundice disorders                                        transaminases
Hepatitis

Skin and                          Pruritus                                              Stevens-Johnson subcutaneous                                                                            syndrome, Drug tissue disorders                  Rash                                                  reaction with eosinophilia and
Urticaria systemic symptoms
(DRESS)

Musculo-         Myalgia                         Myopathy             Arthralgia        Tendon skeletal and                                     (including                             disorders, connective                                       myositis)                              sometimes tissue disorders                                                                        complicated by Rhabdomyolysis                         rupture
Lupus-like                             Immune- syndrome                               mediated
Muscle rupture                         necrotising myopathy

Renal and                                                             Haematuria urinary disorders

Reproductive                                                          Gynaecomastia system and breast disorders

General            Asthenia                                                             Oedema disorders and administration site conditions
1 Frequencywill 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).

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 Crestor. 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 Crestor 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 Crestor-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 (>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.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il