Revised year |
2018 |
2019 |
2018 |
2019 |
Detect of hepatotoxicity |
Pretreatment |
Pretreatment |
Pretreatment |
Pretreatment |
Consider at 4–12 weeks (not routinely) |
At 4 weeks (ALT + T.bil) |
Consider if symptoms are present (AST+ALT, not routinely) |
At 8–12 weeks |
Definition of hepatotoxicity |
ALT ≥ 3× UNL, two times |
ALT > 3× UNL or |
ALT ≥ 3× UNL |
ALT ≥ 3× UNL |
T.bil > 2× UNL |
Coping with hepatotoxicity |
ALT ≥ 3× UNL |
ALT > 3× UNL and T.bil > 2× UNL→Stop |
ALT ≥ 3× UNL |
ALT ≥ 3× UNL |
→ Recheck |
ALT ≤ 3× UNL or T.bil ≤ 2× UNL→ Consider stop |
→ Dose reduction or alternative statins |
→ Stop |
→ ALT ≥ 3× UNL, stop |
ALT ≤ 3× UNL and T.bil ≤ 2× UNL→ Recheck at 2–4 weeks |
|
→ Recheck at 4–6 weeks |
|
|
|
ALT < 3× UNL |
|
|
|
→ Continue |
Detect of myopathy |
Pretreatment |
Pretreatment |
Identify predisposing factors |
Pretreatment |
Consider if symptoms are present (not routinely) |
At 4 weeks |
Consider if symptoms are present (not routinely) |
Consider if symptoms are present (not routinely) |
Coping with myopathy |
CK ≥ 10× UNL |
CK ≥ 10× UNL and symptoms |
Not specifically mentioned |
CK ≥ 10× UNL |
→ Stop |
→ Stop, refer to specialist |
→ Statin discontinuation until symptoms improve |
→ Stop, check every 2 weeks |
4× UNL ≤ CK < 10× UNL |
CK ≥ 10× UNL and no symptoms |
→ Rechallenge with a reduced dose, alternative agent, or alternative dosing regimen |
CK < 10× UNL and symptoms |
→ Stop, monitor |
→ Stop, recheck at 4-6 weeks |
|
→ Stop, monitor |
CK < 4× UNL |
4× UNL ≤ CK < 10× UNL and symptoms |
|
CK < 10× UNL and no symptoms |
→ Restart after 2–4 weeks |
→ Stop, recheck at 4-6 weeks |
|
→ Continue, check every 2 weeks |
|
4× UNL ≤ CK < 10× UNL and no symptoms |
|
CK < 4× UNL |
|
→ Continue, recheck at 2–4 weeks |
|
→ Continue, if symptoms occur, monitor CK regularly |
|
CK < 4× UNL and symptoms |
|
|
|
→ Continue, recheck at 2–4 weeks |
|
|
|
CK < 4× UNL and no symptoms |
|
|
|
→ Continue |
|
|