Table 3. Common adverse events of MKIs.
| MKI most frequently involved (frequency of any grade of AE) | Management | |
|---|---|---|
| Fatigue and loss of weight | All (26-59%) | Increase or at least maintain physical activity; take pills in the evening Monitor other causes (e.g., anemia, depression, electrolyte disturbance, hypothyroidism) |
| Diarrhea | All (30-68%) | Loperamide and/or codeine Dietary changes (eat low-fiber foods; avoid high-fat or spicy foods, alcohol, and caffeinated or carbonated drinks) |
| HTA | All (30-67%) | Monitor blood pressure at least once a week Diuretics, ACEIs, ARBs, BBs, or CCBs alone or in combination Avoid diltiazem, verapamile, and nifedipine |
| Rash | All (20-50%) | Use perfume-free soaps and wear loose, natural-fabric clothing; avoid hot or cold water Topical corticosteroids or antihistamines |
| TSH increase | All (30-60%) | Monitor TSH levels monthly and adjust thyroid-replacement medication dose |
| Hand-foot syndrome | Sorafenib (76%) | Prevention: local care of feet and hands, urea cream 10% on hands and feet, use cotton socks Treatment: Thick urea-based cream (30%), topical lidocaine Use comfortable shoes and avoid hot/cold water NSAIDs, codeine, or pregabalin |
| Alopecia | Sorafenib (67%) | Inform the patient that it is temporary, usually recovering after the treatment, and does not require any treatment |
| Proteinuria | Lenvatinib (31%) | If ≥ 2 g/24 hours: withhold treatment Resume at reduced dose when proteinuria is < 2 g/24 hours Discontinue if nephrotic syndrome |
| Mucositis | All (30%) | Mouthwash with lidocaine + sucralfate, salt and sodium bicarbonate, or chlorhexidine |
| Hypocalcemia | Sorafenib (18%) | Monitor blood calcium levels at least monthly and replace calcium + vitamin D as necessary |
| QTc prolongation | Vandetanib (23%, G > 3 in 14%) | Serially monitor ECG and electrolytes and correct any abnormality Avoid drugs known to prolong QTc Discontinue MKIs if QTc ≥ 500 msec |
AEs: adverse events; ACEI: angiotensin converting enzyme inhibitor; ARB: angiotensin II receptor blockers; BB: beta-blockers; CCB: calcium channel blockers; NSAID: non steroidal anti-inflammatory drugs.