
Treatment dosing
A Single Infusion of CYRAMZA, Prior to FOLFIRI, Every 2 Weeks1
Recommended dose1

The recommended dose of CYRAMZA in combination with irinotecan, folinic acid, and fluorouracil (FOLFIRI) is 8 milligrams per kilogram on day 1 of a 14-day cycle with an infusion time of 60 minutes. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. CYRAMZA should be administered as an intravenous (IV) infusion only. Do not administer as IV push or bolus. Continue CYRAMZA until disease progression or unacceptable toxicity. In the event of a grade 1 or 2 infusion-related reaction (IRR), reduced infusion rate by 50 percent.
FOLFIRI was administered on Day 1 of a 14-day cycle. The recommended dose of FOLFRI is irinotecan 180 milligrams per meter squared with an infusion time of 90 minutes; folinic acid 400 milligram per meter squared with an infusion time of 120 minutes; fluorouracil bolus at a dose of 400 milligrams per meter squared with an infusion time of 2-4 minutes, and fluorouracil infusion at a dose of 2400 milligrams per meter squared with an infusion time of 46 to 48 hours. Irinotecan and folinic acid IV simultaneously; followed by fluorouracil 400 milligrams per meter squared bolus; followed by fluorouracil 2400 milligrams per meter squared IV by continuous infusion over 46 to 48 hours.
* For intravenous (IV) infusion only. Do not administer as IV push or bolus. Continue CYRAMZA until disease progression or unacceptable toxicity. In the event of a grade 1 or 2 infusion-related reaction (IRR), reduce infusion rate by 50%.
† Irinotecan and folinic acid IV simultaneously; followed by fluorouracil 400 mg/m2 IV bolus; followed by fluorouracil 2400 mg/m2 IV by continuous infusion over 46 to 48 hours.
- Prior to each CYRAMZA infusion, premedicate all patients with an IV histamine H1 antagonist (eg, diphenhydramine hydrochloride)1
- For patients who have experienced a grade 1 or 2 IRR, also premedicate with dexamethasone (or equivalent) and acetaminophen prior to each CYRAMZA infusion1
- Administer CYRAMZA prior to administration of FOLFIRI1
See Prescribing Information for irinotecan, folinic acid, and fluorouracil for toxicities and dosage recommendations
SELECT IMPORTANT SAFETY INFORMATION
Infusion-Related Reactions
- IRR, including severe and life threatening IRR, occurred in CYRAMZA clinical trials. Symptoms of IRR included rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, and paresthesia. In severe cases, symptoms included bronchospasm, supraventricular tachycardia, and hypotension. In 2137 patients with various cancers treated with CYRAMZA in which premedication was recommended or required, the incidence of all Grade IRR ranged from <1-9%. Grade 3-5 IRR incidence was <1%.
- Premedicate prior to each CYRAMZA infusion. Monitor patients during the infusion for signs and symptoms of IRR in a setting with available resuscitation equipment. Reduce the infusion rate by 50% for Grade 1-2 IRR. Permanently discontinue CYRAMZA for Grade 3-4 IRR.
Dose modifications for CYRAMZA in metastatic CRC1
If specific adverse events are observed, these dosing modifications are recommended for CYRAMZA when treating patients with metastatic colorectal cancer (mCRC).
CYRAMZA should be permanently discontinued if a Grade 3 or 4 hemorrhage is observed.
CYRAMZA should be permanently discontinued when gastrointestinal perforations (all grades) are observed.
For wound healing complications (all grades), withhold CYRAMZA for 28 days prior to elective surgery and resume CYRAMZA no sooner than 2 weeks after surgery and until adequate wound healing. The safety of resumption of CYRAMZA after resolution of wound healing complications has not been established.
CYRAMZA should be permanently discontinued when there are arterial thromboembolic events (all grades).
For severe hypertension, withhold CYRAMZA until controlled with medical management. If severe hypertension cannot be controlled with antihypertensive therapy, permanently discontinue CYRAMZA.
Reduce the infusion rate of CYRAMZA by 50 percent if Grade 1 or 2 infusion-related reactions (IRRs) occur. Permanently discontinue CYRAMZA for Grade 3 or 4 IRRs.
For all grades of posterior reversible encephalopathy syndrome (PRES), permanently discontinue CYRAMZA.
For the first occurrence of increased urine protein levels (proteinuria) greater than or equal to 2 grams per 24 hours, withhold CYRAMZA until urine protein level is less than 2 gram per 24 hours. Resume CYRAMZA at a reduced dose (from 8 milligrams to 6 milligrams). For reoccurrence of urine protein levels greater than 2 grams per 24 hours following initial dose reduction, withhold CYRAMZA until urine protein level is less than 2 gram per 24 hours. Resume CYRAMZA at a reduced dose (from 6 milligrams to 5 milligrams). Permanently discontinue CYRAMZA if urine protein levels are greater than 3 grams per 24 hours or in the setting of nephrotic syndrome.
National Cancer Institute Common Toxicity Criteria for Adverse Events Criteria Version 4.0 was used to identify adverse reactions.
‡ National Cancer Institute Common Toxicity Criteria for Adverse Events Criteria Version 4.0 used to identify adverse reactions.
References
- CYRAMZA (ramucirumab) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2021.