Table 4.

Adverse event management strategies—hypertension

Hypertension
Prophylaxis
Monitor BP before initiation of cabozantinib using a minimum of two standardized BP measurements alongside patient history, physical assessment, directed laboratory evaluation, and an instrument test to determine cardiovascular risk factors [92, 127]
Educate patients on BP self-monitoring and advise they keep a BP log [113]
BP should be well controlled prior to initiating cabozantinib; ensure patients who have already been prescribed antihypertensive therapy are adherent and that therapy has been titrated to effective doses [92, 127]
Check for potential drug-drug interactions of existing antihypertensive agents with cabozantinib (Supplementary Table 2)
Consider effects of concomitant medications on BP (e.g., anti-inflammatory drugs can increase BP; opiates can lower BP) [92]
Monitor BP during cabozantinib treatment (weekly during first cycle; every ≥ 2–3 weeks thereafter) [127]
Supportive care
Add antihypertensive medications or increase dose of existing medication as indicated [92, 108]
Patients with portal hypertension should be treated with nonselective beta-blockers [95]
The antihypertensive agent should be carefully considered owing to potential inhibition of CYP3A4 [63, 128] (Supplementary Table 2)
Thiazides, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers may be used to treat hypertension and are not known CYP3A4 substrates [98–100, 128]
Thiazide diuretics should be prescribed with caution owing to the associated risk of diarrhea [63]
Diltiazem and verapamil are moderate inhibitors of CYP3A4 [99]
Amlodipine, felodipine, lercanidipine, nisoldipine, and nifedipine are not considered to be CYP3A4 inhibitors [99]

BP blood pressure, CYP3A4 cytochrome P450 3A4