Cyramza Dosage/Direction for Use

Ramucirumab therapy must be initiated and supervised by physicians experienced in oncology.
Posology: Gastric cancer and gastro-oesophageal junction (GEJ) adenocarcinoma: Cyramza in combination with paclitaxel: The recommended dose of ramucirumab is 8 mg/kg on days 1 and 15 of a 28 day cycle, prior to paclitaxel infusion. The recommended dose of paclitaxel is 80 mg/m² administered by intravenous infusion over approximately 60 minutes on days 1, 8 and 15 of a 28 day cycle. Prior to each paclitaxel infusion, patients should have a complete blood count and blood chemistry performed to evaluate hepatic function. Criteria to be met prior to each paclitaxel infusion are provided in Table 7. (See Table 7.)

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Cyramza as a single agent: The recommended dose of ramucirumab as a single agent is 8 mg/kg every 2 weeks.
Colorectal cancer: The recommended dose of ramucirumab is 8 mg/kg every 2 weeks administered by intravenous infusion, prior to FOLFIRI administration. Prior to chemotherapy, patients should have a complete blood count. Criteria to be met prior to FOLFIRI are provided in Table 8. (See Table 8.)

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Non-small cell lung cancer (NSCLC): Cyramza in combination with erlotinib for the treatment of NSCLC with activating EGFR mutations: The recommended dose of ramucirumab in combination with erlotinib is 10 mg/kg every two weeks.
EGFR mutation status should be determined prior to initiation of treatment with ramucirumab and erlotinib using a validated test method. See erlotinib prescribing information for the posology and method of administration of erlotinib.
Cyramza in combination with docetaxel for the treatment of NSCLC after platinum-based chemotherapy: The recommended dose of ramucirumab is 10 mg/kg on day 1 of a 21 day cycle, prior to docetaxel infusion. The recommended dose of docetaxel is 75 mg/m² administered by intravenous infusion over approximately 60 minutes on day 1 of a 21 day cycle. For East Asian patients, a reduced docetaxel starting dose of 60 mg/m² on day 1 of a 21 day cycle should be considered. See docetaxel prescribing information for specific dosing advice.
Hepatocellular carcinoma (HCC): The recommended dose of ramucirumab as a single agent is 8 mg/kg every 2 weeks.
Alpha fetoprotein (AFP) testing in HCC: Patients with HCC should be selected based on a serum AFP concentration of ≥ 400 ng/ml with a validated AFP test prior to ramucirumab treatment (see Pharmacology: Pharmacodynamics under Actions).
Duration of treatment: It is recommended that treatment be continued until disease progression or until unacceptable toxicity has occurred.
Premedication: Premedication is recommended with a histamine H1 antagonist (for example diphenhydramine) prior to infusion of ramucirumab. If a patient experiences a Grade 1 or 2 infusion-related reaction premedication must be given for all subsequent infusions. If a patient experiences a second Grade 1 or 2 infusion-related reaction (IRR) administer dexamethasone (or equivalent); then, for subsequent infusions, premedicate with the following or equivalent medicinal products: an intravenous histamine H1 antagonist (for example diphenhydramine hydrochloride), paracetamol and dexamethasone.
See prescribing information for paclitaxel, for components of FOLFIRI and for docetaxel, as applicable, for premedication requirements and additional information.
Posology adjustments for ramucirumab: Infusion-related reactions: The infusion rate of ramucirumab should be reduced by 50% for the duration of the infusion and all subsequent infusions if the patient experiences a grade 1 or 2 IRR. Ramucirumab should be immediately and permanently discontinued in the event of a grade 3 or 4 IRR (see Precautions).
Hypertension: The blood pressure of patients should be monitored prior to each ramucirumab administration and treated as clinically indicated. Ramucirumab therapy should be temporarily discontinued in the event of severe hypertension, until controlled with medical management. If there is medically significant hypertension that cannot be controlled safely with antihypertensive therapy, ramucirumab therapy should be permanently discontinued (see Precautions).
Proteinuria: Patients should be monitored for the development or worsening of proteinuria during ramucirumab therapy. If the urine protein is ≥2+ on a dipstick, a 24 hour urine collection should be performed. Ramucirumab therapy should be temporarily discontinued if the urine protein level is ≥2 g/24 hours. Once the urine protein level returns to <2 g/24 hours, treatment should be resumed at a reduced dose level (see Table 9). A second dose reduction (see Table 9) is recommended if a urine protein level ≥2 g/24 hours reoccurs.
Ramucirumab therapy should be permanently discontinued if the urine protein level is >3 g/24 hours or in the event of nephrotic syndrome. (See Table 9.)

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Elective surgery or impaired wound healing: Ramucirumab therapy should be temporarily discontinued for at least 4 weeks prior to elective surgery. Ramucirumab therapy should be temporarily discontinued if there are wound healing complications, until the wound is fully healed (see Precautions).
Permanent discontinuation: Ramucirumab therapy should be permanently discontinued in the event of: Severe arterial thromboembolic events (see Precautions); Gastrointestinal perforations (see Precautions); Severe bleeding: NCI CTCAE Grade 3 or 4 bleeding (see Precautions); Spontaneous development of fistula (see Precautions); Hepatic encephalopathy or hepatorenal syndrome (see Precautions).
Paclitaxel dose adjustments: Paclitaxel dose reductions may be applied based upon the grade of toxicity experienced by the patient. For NCI CTCAE Grade 4 haematological toxicity or Grade 3 paclitaxel-related non-haematological toxicity, it is recommended to reduce the paclitaxel dose by 10 mg/m² for all following cycles. A second reduction of 10 mg/m² is recommended if these toxicities persist or reoccur.
FOLFIRI dose adjustments: Dose reductions for individual components of FOLFIRI may be made for specific toxicities. Dose modifications of each component of FOLFIRI should be made independently and are provided in Table 10. Table 11 provides details of dose delays or dose reductions of components of FOLFIRI at the next cycle based on maximum grade of specific adverse drug reactions. (See Tables 10 and 11.)

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Docetaxel dose adjustments: Docetaxel dose reductions may be applied based upon the grade of toxicity experienced by the patient. Patients who experience either febrile neutropenia, neutrophils <500 cells/mm³ for more than 1 week, severe or cumulative cutaneous reactions, or other Grade 3 or 4 non-haematological toxicities during docetaxel treatment should have treatment withheld until resolution of the toxicity. It is recommended to reduce the docetaxel dose by 10 mg/m² for all following cycles. A second reduction of 15 mg/m² is recommended if these toxicities persist or reoccur. In this case, East Asian patients with a starting dose of 60 mg/m² should have docetaxel treatment discontinued (see Posology as previously mentioned).
Special populations: Elderly: In the pivotal studies there is limited evidence that patients 65 years of age or older are at increased risk of adverse events compared to patients younger than 65 years old. No dose reductions are recommended (see Precautions and Pharmacology: Pharmacodynamics under Actions).
Renal impairment: There have been no formal studies with Cyramza in patients with renal impairment. Clinical data suggest that no dose adjustments are required in patients with mild, moderate or severe renal impairment (see Precautions and Pharmacology: Pharmacokinetics under Actions). No dose reductions are recommended.
Hepatic impairment: There have been no formal studies with Cyramza in patients with hepatic impairment. Clinical data suggest that no dose adjustments are required in patients with mild or moderate hepatic impairment. There are no data regarding ramucirumab administration in patients with severe hepatic impairment (see Precautions and Pharmacology: Pharmacokinetics under Actions). No dose reductions are recommended.
Paediatric population: The safety and efficacy of Cyramza in children and adolescents (<18 years) has not been established. Currently available data are described in Adverse Reactions, Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions. Due to limited data no recommendation on posology can be made.
There is no relevant use of ramucirumab in the paediatric population for the indications of advanced gastric cancer or gastro-oesophageal adenocarcinoma, adenocarcinoma of the colon and rectum, lung carcinoma, and hepatocellular carcinoma.
Method of administration: Cyramza is for intravenous use. After dilution, Cyramza is administered as an intravenous infusion over approximately 60 minutes. It should not be administered as an intravenous bolus or push. To achieve the required infusion duration of approximately 60 minutes, the maximum infusion rate of 25 mg/minute should not be exceeded, instead the infusion duration should be increased. The patient should be monitored during infusion for signs of infusion-related reactions (see Precautions) and the availability of appropriate resuscitation equipment should be ensured.
For instructions on dilution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.