Cholib Adverse Reactions

Summary of the safety profile: The most commonly reported adverse drug reactions (ADRs) during Cholib 145 mg/20 mg film-coated tablet therapy are increased blood creatinine, upper respiratory tract infection, increased platelet count, gastroenteritis and increased alanine-aminotransferase.
Tabulated list of adverse reactions: During four double blind clinical trials of 24-week duration 1,237 patients have received treatment with co-administered fenofibrate and simvastatin. In a pooled analysis of these four trials, the rate of discontinuation due to treatment emergent adverse reactions was 5.0% (51 subjects on 1012) after 12 weeks of treatment with fenofibrate and simvastatin 145 mg/20 mg per day and 1.8% (4 subjects on 225) after 12 weeks of treatment with fenofibrate and simvastatin 145 mg/40 mg per day.
Treatment emergent adverse reactions reported in patients receiving co-administration of fenofibrate and simvastatin occurring are listed as follows by system organ class and frequency.
The adverse reactions of Cholib 145 mg/20 mg film-coated tablet are in line with what is known from its two active substances: fenofibrate and simvastatin.
The frequencies of adverse reactions are ranked according to the following: very common (≥ 1/10), 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) and not known (cannot be estimated from the available data).
Adverse reactions observed with the co-administration of fenofibrate and simvastatin (Cholib 145 mg/20 mg film-coated tablet). (See Table 3.)

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Description of selected adverse reactions: Blood creatinine increased: 10% of patient had a creatinine increase from baseline greater than 30 μmol/L with co-administered fenofibrate and simvastatin versus 4.4% with statin monotherapy. 0.3% of patients receiving co-administration had clinically relevant increases in creatinine to values >200 μmol/l.
Additional information on the individual active substances of the fixed dose combination: Additional adverse reactions associated with the use of medicinal products containing simvastatin or fenofibrate observed in clinical trials and postmarketing experience that may potentially occur with Cholib 145 mg/20 mg tablet are listed as follows. (See Table 4.)

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Description of selected adverse reactions: Pancreatitis: * In the FIELD study, a randomised placebo-controlled trial performed in 9795 patients with type 2 diabetes mellitus, a statistically significant increase in pancreatitis cases was observed in patients receiving fenofibrate versus patients receiving placebo (0.8% versus 0.5%; p=0.031).
Thromboembolism: * In the FIELD study, a statistically significant increase was reported in the incidence of pulmonary embolism (0.7% [32/4900 patients] in the placebo group versus 1.1% [53/4895 patients] in the fenofibrate group; p = 0.022) and a statistically non-significant increase in deep vein thrombosis (placebo: 1.0% [48/4900 patients] versus fenofibrate 1.4% [67/4895 patients]; p=0.074).
Myopathy: ** In a clinical trial, myopathy occurred commonly in patients treated with simvastatin 80 mg/day compared to patients treated with 20 mg/day (1.0% vs 0.02%, respectively).
Hypersensitivity syndrome: *** 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, erythrocyte sedimentation rate (ESR) increased, arthritis and arthralgia, urticaria, photosensitivity, fever, flushing, dyspnoea and malaise.
Diabetes mellitus: **** Diabetes mellitus: Patients at risk (fasting glucose 5.6 to 6.9 mmol/L, BMI>30 kg/m², raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.
Increased blood homocysteine level: ***** In the FIELD study the average increase in blood homocysteine level in patients treated with fenofibrate was 6.5 μmol/L, and was reversible on discontinuation of fenofibrate treatment.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.