Nilemdo Adverse Reactions

Summary of the safety profile: The most commonly reported adverse reactions with bempedoic acid during pivotal trials were hyperuricaemia (3.8%), pain in extremity (3.1%), anaemia (2.5%), and gout (1.4%). More patients on bempedoic acid compared to placebo discontinued treatment due to muscle spasms (0.7% versus 0.3%), diarrhoea (0.5% versus <0.1%), pain in extremity (0.4% versus 0), and nausea (0.3% versus 0.2%), although differences between bempedoic acid and placebo were not significant.
Tabulated list of adverse reactions: Adverse reactions reported with bempedoic acid, based on incidence rates from phase 3 primary hyperlipidaemia studies and exposure adjusted incidence rates from CLEAR Outcomes study, are displayed by system organ class and frequency in Table 4. (See Table 4.)
Frequencies are defined as: 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).

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Description of selected adverse reactions: Hepatic enzyme elevations: Increases in serum transaminases (AST and/or ALT) have been reported with bempedoic acid. In the phase 3 primary hyperlipidaemia studies, the incidence of elevations (≥3× ULN) in hepatic transaminase levels was 0.7% for patients treated with bempedoic acid and 0.3% for placebo. In the CLEAR Outcomes study, the incidence of elevations >3× ULN in hepatic transaminase levels also occurred more frequently in bempedoic acid-treated patients (1.6%) than in placebo-treated patients (1.0%). These elevations in transaminases were not associated with other evidence of liver dysfunction (see Precautions).
Increased serum uric acid: Increases in serum uric acid were observed in clinical trials with bempedoic acid possibly related to inhibition of renal tubular OAT2 (see Interactions). In the phase 3 primary hyperlipidemia studies, a mean increase of 47.6 micromole/L (0.8 mg/dL) in uric acid compared to baseline was observed with bempedoic acid at week 12. The elevations in serum uric acid usually occurred within the first 4 weeks of treatment and returned to baseline following discontinuation of treatment. In the phase 3 primary hyperlipidemia studies, gout was reported in 1.4% of patients treated with bempedoic acid and 0.4% of patients treated with placebo (see Precautions). In the CLEAR Outcomes study, a mean increase of 47.6 micromole/L (0.8 mg/dL) in uric acid compared to baseline was observed in bempedoic acid-treated patients at month 3, and gout was also reported more frequently in bempedoic acid-treated patients (3.1%) than placebo-treated patients (2.1%). In both treatment groups, patients who reported gout were more likely to have a medical history of gout and/or baseline levels of uric acid above the ULN.
Effects on serum creatinine and blood urea nitrogen: Bempedoic acid has been shown to increase serum creatinine and blood urea nitrogen (BUN). In the phase 3 primary hyperlipidemia studies, a mean increase of 4.4 micromole/L (0.05 mg/dL) in serum creatinine and a mean increase of 0.61 mmol/L (1.7 mg/dL) in BUN compared to baseline was observed with bempedoic acid at week 12. The elevations in serum creatinine and BUN usually occurred within the first 4 weeks of treatment, remained stable, and returned to baseline following discontinuation of treatment. Similar mean increases in serum creatinine (5.8 micromole/L (0.066 mg/dL)) and BUN (0.82 mmol/L (2.3 mg/dL)) were observed with bempedoic acid in the CLEAR Outcomes study.
The observed elevations in serum creatinine may be associated with bempedoic acid inhibition of OAT2-dependent renal tubular secretion of creatinine (see Interactions), representing a drug-endogenous substrate interaction and does not appear to indicate worsening renal function. This effect should be considered when interpreting changes in estimated creatinine clearance in patients on Nilemdo therapy, particularly in patients with medical conditions or receiving medicinal products that require monitoring of estimated creatinine clearance.
Decreased haemoglobin: Decreases in haemoglobin were observed in clinical trials with bempedoic acid. In the phase 3 primary hyperlipidaemia studies, a decrease in haemoglobin from baseline of ≥20 g/L and < lower limit of normal (LLN) was observed in 4.6% of patients in the bempedoic acid group compared with 1.9% of patients on placebo. Greater than 50 g/L and < LLN decreases in haemoglobin were reported at similar rates in bempedoic acid and placebo groups (0.2% versus 0.2%, respectively). The decreases in haemoglobin usually occurred within the first 4 weeks of treatment and returned to baseline following discontinuation of treatment. Among patients who had normal haemoglobin values at baseline, 1.4% in the bempedoic acid group and 0.4% in the placebo group experienced haemoglobin values below LLN while on treatment. In the phase 3 primary hyperlipidemia studies, anaemia was reported in 2.5% of patients treated with bempedoic acid and 1.6% of patients treated with placebo. In the CLEAR Outcomes study, similar decreases in haemoglobin were observed, and anaemia was also reported more frequently in bempedoic acid-treated patients (4.7%) compared to placebo-treated patients (3.9%).
Elderly population: Of the 3,621 patients treated with bempedoic acid in the phase 3 primary hyperlipidemia studies, 2,098 (58%) were >65 years old. In the CLEAR Outcomes study, 4,141 patients (59%) treated with bempedoic acid were ≥65 years of age and 1,066 patients (15%) treated with bempedoic acid were ≥75 years of age. No overall difference in safety was observed between elderly and the younger population.
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. Healthcare professionals are asked to report any suspected adverse reactions according to local requirement.