Adverse Reaction

Severitya 

Recommended Dose Modification

IRRs

Grade 1 or 2

Reduce the infusion rate of ramucirumab by 50%.

Grade 3 or 4

Permanently discontinue ramucirumab.

Hypertension

Severe hypertension

Withhold ramucirumab until controlled with medical management.

Severe hypertension that cannot be controlled with antihypertensive therapy 

Permanently discontinue ramucirumab.

Proteinuria

First occurrence of increased urine protein levels ≥2 g/24 hours

Withhold ramucirumab until urine protein level is <2 g/24 hours. When resuming treatment, reduce the dose to

• 6 mg/kg if original dose was 8 mg/kg, or
• 8 mg/kg if original dose was 10 mg/kg.

Reoccurrence of urine protein level >2 g/24 hours following initial dose reduction

Withhold ramucirumab until urine protein level is <2 g/24 hours. When resuming treatment, further reduce the dose to

• 5 mg/kg if initial reduced dose was 6 mg/kg, or
• 6 mg/kg if initial reduced dose was 8 mg/kg.

Urine protein level >3 g/24 hours or in the setting of nephrotic syndrome

Permanently discontinue ramucirumab.

Wound-healing complications

All grades

Withhold ramucirumab for 28 days prior to elective surgery. Do not administer ramucirumab for at least 2 weeks following surgery and until adequate wound healing. The safety of resumption of ramucirumab after resolution of wound healing complications has not been established.

ATE, GI perforation, PRES

All grades

Permanently discontinue ramucirumab.

Hemorrhage

Grade 3 or 4