Drug Detail:Cyramza (Ramucirumab [ ra-mue-sir-ue-mab ])
Generic Name: ramucirumab 10mg in 1mL
Dosage Form: intravenous infusion
Drug Class: VEGF/VEGFR inhibitors
Premedication
- Prior to each CYRAMZA infusion, premedicate all patients with an intravenous histamine-1 receptor antagonist (e.g., diphenhydramine hydrochloride) [see Warnings and Precautions (5.6)].
- For patients who have experienced a Grade 1 or 2 IRR, premedicate with a histamine-1 receptor antagonist, dexamethasone (or equivalent), and acetaminophen prior to each CYRAMZA infusion [see Dosage and Administration (2.6)].
Recommended Dosage for Gastric Cancer
- The recommended dosage of CYRAMZA, either as a single agent or in combination with weekly paclitaxel, is 8 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.
- When given in combination with paclitaxel, administer CYRAMZA prior to administration of paclitaxel.
- Refer to the prescribing information for paclitaxel for dosage information.
Recommended Dosage for Non-Small Cell Lung Cancer
EGFR Exon 19 Deletions or Exon 21 (L858R) Substitution Mutations – CYRAMZA in Combination with Erlotinib
- The recommended dosage of CYRAMZA is 10 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.
- Refer to the prescribing information for erlotinib for dosage information.
Disease Progression On Or After Platinum-based Chemotherapy – CYRAMZA in Combination with Docetaxel
- The recommended dosage of CYRAMZA is 10 mg/kg administered by intravenous infusion over 60 minutes on Day 1 of a 21-day cycle prior to docetaxel infusion. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.
- Refer to the prescribing information for docetaxel for dosage information.
Recommended Dosage for Colorectal Cancer
- The recommended dosage of CYRAMZA is 8 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes prior to FOLFIRI administration. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.
- Refer to the prescribing information for fluorouracil, leucovorin, and irinotecan for dosage information.
Recommended Dosage for Hepatocellular Carcinoma
- The recommended dosage of CYRAMZA is 8 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes. If the first infusion is tolerated, all subsequent CYRAMZA infusions may be administered over 30 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.
Dosage Modifications for Adverse Reactions
Reduce dose, withhold dose, or discontinue CYRAMZA to manage adverse reactions as described in Table 1.
| Adverse Reaction | Severitya | Dosage Modification |
|---|---|---|
|
a National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0 used to identify adverse reactions |
||
| Hemorrhage [see Warnings and Precautions (5.1)] |
Grade 3 or 4 | Permanently discontinue CYRAMZA |
| Gastrointestinal Perforation [see Warnings and Precautions (5.2)] |
All Grades | Permanently discontinue CYRAMZA |
| Wound Healing Complications [see Warnings and Precautions (5.3)] |
All Grades |
|
| Arterial Thromboembolic Events [see Warnings and Precautions (5.4)] |
All Grades | Permanently discontinue CYRAMZA |
| Hypertension [see Warnings and Precautions (5.5)] |
Severe hypertension | Withhold CYRAMZA until controlled with medical management |
| Severe hypertension that cannot be controlled with antihypertensive therapy | Permanently discontinue CYRAMZA | |
| Infusion-Related Reaction (IRR) [see Dosage and Administration (2.1), Warnings and Precautions (5.6)] |
Grade 1 or 2 IRR | Reduce the infusion rate of CYRAMZA by 50% |
| Grade 3 or 4 IRR | Permanently discontinue CYRAMZA | |
| Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions (5.8)] | All Grades | Permanently discontinue CYRAMZA |
| Proteinuria [see Warnings and Precautions (5.9)] |
First occurrence of increased urine protein levels greater than or equal to 2 g per 24 hours |
|
| Reoccurrence of urine protein level greater than 2 g per 24 hours following initial dose reduction |
|
|
| Urine protein level greater than 3 g per 24 hours or in the setting of nephrotic syndrome | Permanently discontinue CYRAMZA | |
Preparation and Administration
Preparation
- Visually inspect vials for particulate matter and discoloration. Discard if particulate matter or discolorations are identified.
- Calculate the dose and the required volume of CYRAMZA needed for the calculated dose.
- Withdraw the required volume of CYRAMZA and further dilute with only 0.9% Sodium Chloride Injection in an intravenous infusion container to a final volume of 250 mL. Do not use dextrose containing solutions.
- Do not shake. Gently invert the container to ensure adequate mixing.
- Do not dilute with other solutions or co-infuse with other electrolytes or medications.
- Do not freeze. Store diluted solution for no more than 24 hours at 2°C to 8°C (36°F to 46°F) or 4 hours at room temperature (below 25°C [77°F]).
- Discard any unused portion of CYRAMZA.
Administration
- Visually inspect the diluted solution for particulate matter and discoloration prior to administration. Discard if particulate matter or discolorations are identified.
- Do not administer CYRAMZA as an intravenous push or bolus.
- Administer diluted CYRAMZA solution via infusion pump through a separate infusion line. Use of a protein sparing 0.22 micron filter is recommended.
- Flush the line with sterile 0.9% Sodium Chloride Injection at the end of the infusion.
