The frequencies of the following adverse events which have been reported during clinical studies and/or post-marketing use are categorized based on an assessment of their incidence rates in large, long-term, placebo-controlled, clinical trials including HPS and 4S with 20,536 and 4444 patients, respectively (see Pharmacology: Pharmacodynamics under Actions). For HPS, only serious adverse events were recorded as well as myalgia, increases in serum transaminases and CK. For 4S, all the adverse events listed in the following text were recorded. If the incidence rates on simvastatin were less than or similar to that of placebo in these trials and there were similar reasonable causally related spontaneous report events, these adverse events are categorized as rare.
In HPS (see Pharmacology: Pharmacodynamics under Actions) involving 20,536 patients treated with Priacin 40 mg/day (n=10,269) or placebo (n=10,267), the safety profiles were comparable between patients treated with simvastatin 40 mg and patients treated with placebo over the mean 5 yrs of the study. Discontinuation rates due to side effects were comparable (4.8% in patients treated with simvastatin 40 mg compared with 5.1% in patients treated with placebo). The incidence of myopathy was <0.1% in patients treated with simvastatin 40 mg. Elevated transaminases (>3 x ULN confirmed by repeat test) occurred in 0.21% (n=21) of patients treated with simvastatin 40 mg compared with 0.09% (n=9) of patients treated with placebo.
The frequencies of adverse events are ranked according to the following: Very common (>1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000) including isolated reports.
Blood and Lymphatic System Disorders: Rare: Anaemia.
Nervous System Disorders: Rare: Headache, paresthesia, dizziness, peripheral neuropathy. There has been rare post-marketing reports of cognitive impairment (eg, memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally non-serious and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks). Very Rare: Memory impairment.
Gastrointestinal Disorders: Rare: Constipation, abdominal pain, flatulence, dyspepsia, diarrhoea, nausea, vomiting, pancreatitis.
Hepatobiliary Disorders: Rare: Hepatitis/jaundice. Very Rare: Hepatic failure.
Skin and Subcutaneous Tissue Disorders: Rare: Rash, pruritus, alopecia.
Musculoskeletal, Connective Tissue and Bone Disorders: Rare: Myopathy, rhabdomyolysis (see Precautions), myalgia, muscle cramps. Myopathy has been rarely reported.
Psychiatric Disorders: Very Rare: Insomnia.
The following adverse events have been reported with some statins: Sleep disturbances including insomnia and nightmares, sexual dysfunction, depression, exceptional cases of interstitial lung disease especially with long-term therapy (see Precautions).
General Disorders and Administration Site Conditions: Rare: Asthenia.
An apparent hypersensitivity syndrome has been reported rarely which has included some of the following features: Angioedema, lupus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis and arthralgia, urticaria, photosensitivity, fever, flushing, dyspnoea and malaise.
Investigations: Rare: Increases in serum transaminases (alanine or aspartate aminotransferase, γ-glutamyl transpeptidase) (see Hepatic Effects under Precautions), alkaline phosphatase; serum CK levels (see Precautions). Increases in HbA1c and fasting serum glucose levels have been reported with statins.