Usual Adult Dose for Colorectal Cancer

4 mg/kg IV over 1 hour every 2 weeks; administer this drug prior to any component of the FOLFIRI regimen on the day of treatment

• Duration of therapy: until disease progression or unacceptable toxicity

Use: This drug in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Discontinue this drug for:

• Severe hemorrhage
• GI perforation
• Compromised wound healing
• Fistula formation
• Hypertensive crisis or hypertensive encephalopathy
• Arterial thromboembolic events
• Nephrotic syndrome or thrombotic microangiopathy (TMA)
• Reversible posterior leukoencephalopathy syndrome (RPLS)

Temporarily suspend this drug for:

• At least 4 weeks prior to elective surgery
• For recurrent or severe hypertension, until controlled; upon resumption, permanently reduce the dose to 2 mg/kg
• For proteinuria of 2 grams per 24 hours; resume when proteinuria is less than 2 grams per 24 hours. For recurrent proteinuria, suspend this drug until proteinuria is less than 2 grams per 24 hours and then permanently reduce the dose to 2 mg/kg.

Precautions

US BOXED WARNINGS:
HEMORRHAGE:

• Severe, sometimes fatal hemorrhage, including GI hemorrhage, has been reported:

Recommendations:

• Monitor for GI bleeding and other severe bleeding.
• Do not administer this drug to patients with severe hemorrhage.

GI PERFORATION:

• GI perforation, sometimes fatal, has been reported.

Recommendation:

• Discontinue therapy in patients who experience GI perforation.

COMPROMISED WOUND HEALING:

• Severe compromised wound healing has been reported.

Recommendations:

• Discontinue therapy in patients with compromised wound healing.
• Suspend therapy for at least 4 weeks prior to elective surgery, and do not resume therapy for at least 4 weeks following major surgery and until the surgical wound is fully healed.

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Do not re-enter the vial after the initial puncture. Discard any unused portion left in the vial.
• Administer the diluted solution as an IV infusion over 1 hour through a 0.2-micron polyethersulfone filter. Do not use filters made of polyvinylidene fluoride (PVDF) or nylon.
• Do not administer as an IV push or bolus.
• Do not combine this drug with other drugs in the same infusion bag or IV line.
• Administer this drug using an infusion set made of one of the following materials:

PVC containing DEHP or DEHP free PVC containing trioctyl-trimellitate (TOTM) or polypropylene or polyethylene lined PVC or polyurethane

Storage requirements:

• Store unopened vials in a refrigerator at 2C to 8C (36F to 46F). Keep the vials in the original outer carton to protect from light.

Reconstitution/preparation techniques:

• Inspect vials visually prior to use. This drug is a clear, colorless to pale yellow solution. Do not use vial if the solution is discolored or cloudy or if the solution contains particles.
• Withdraw the prescribed dose and dilute in 0.9% sodium chloride solution or 5% dextrose solution for injection to achieve a final concentration of 0.6 to 8 mg/mL.
• Use polyvinyl chloride (PVC) infusion bags containing bis (2-ethylhexyl) phthalate (DEHP) or polyolefin infusion bags.

IV compatibility:

• Compatible with 0.9% sodium chloride solution or 5% dextrose solution

Patient advice:

• This drug can cause severe bleeding; advise patients to contact their health care provider for bleeding or symptoms of bleeding including lightheadedness.
• This drug increases the risk of compromised wound healing; advise patients not to undergo surgery or procedures (including tooth extractions) without discussing with their health care provider.
• This drug can cause or exacerbate existing hypertension; advise patients to undergo routine blood pressure monitoring and to contact their health care provider if blood pressure is elevated or if symptoms from hypertension occur including severe headache, lightheadedness, or neurologic symptoms.
• Advise patients to notify the health care provider of severe diarrhea, vomiting, or severe abdominal pain.
• Advise patients to notify their health care provider of fever or other signs of infection.
• Advise patients of the potential risks to the fetus or neonate using this drug during pregnancy or nursing and of the need to use highly effective contraception in both males and females during and for at least 3 months following last dose. Contact the healthcare provider if pregnancy occurs.