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| Adverse event | Comment | Prevention/intervention |
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| Dyslipidemia | | Comedication with lipid-lowering medication is mandatory (statin not interacting with CYP450 e.g. fluvastatin, or fibrates) |
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| Pancytopenia | | In unexplained cytopenia (white blood cells, red cells, platelets), everolimus may be the cause and dose reduction or temporary cessation may be indicated |
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| Acne | | Improves within a few weeks using local treatment |
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| Aphthous stomatitis | | Local treatment is effective |
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| Angioneurotic edema | | Discontinue ACE inhibitor comedication |
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Creatine kinase (CK) elevation
Muscle cramps | May be related to everolimus overexposure or/and to comedication of statin therapy | Everolimus trough concentration should be adjusted to the lower margin of the target range for several days and/or statin therapy should be stopped temporarily. If this is not effective, consider a temporary switch from everolimus to MMF
In most cases, careful reintroduction of everolimus can be undertaken successfully after normalization of CK level and resolution of muscle cramps.
Selected patients with persistent CK levels > 10-fold higher than normal may be referred for muscle biopsy [5] |
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| Increased proteinuria | May reflect physiological tubular proteinuria due to mTOR inhibition, which is reversible and without clinical relevance as it does not reflect damage to renal tissue
Proteinuria > 1 g/day indicates a glomerular process and may be due to an everolimus-associated event | Concomitant prescription of ACE inhibitor or angiotensin-receptor blockers may reduce the incidence of new onset proteinuria
As proteinuria < 1 g/day does not exclude glomerular damage, urine protein electrophoresis can be performed to detect glomerular proteins |
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| Noninfectious pneumonia | More likely to occur during sirolimus treatment in cancer patients |
Requiring dose reduction or discontinuation and anti-inflammatory treatment by high-dose steroids. Frequent radiologic assessment is mandatory and laboratory values should be monitored twice a week |
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| Impaired wound healing | Elevated risk early postoperatively in high-risk patients (e.g., diabetes, LVAD, redo surgery, and high-dose steroids) due to antiproliferative properties of mTOR inhibitors | Delayed onset of everolimus after transplant surgery, or temporary interruption during subsequent major surgery, may be helpful. In the event of minor local surgery in low-risk patients, everolimus therapy can be continued |
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| Pericardial/pleural effusion | Elevated incidence early after heart transplantation | Manageable by frequent monitoring with echocardiography/sonography, symptomatic diuretic treatment, and drainage on demand |
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