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Zaltrap is a brand name for Aflibercept. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: ZALTRAP in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) chemotherapy is indicated in adults with metastatic colorectal cancer (MCRC) that is resistant to or has progressed after an oxaliplatin-containing regimen.
Verbatim from this product's EMA label. Tap a section to expand.
ZALTRAP should be administered under the supervision of a physician experienced in the use of antineoplastic medicinal products. Posology The recommended dose of ZALTRAP, administered as an intravenous infusion over 1 hour, is 4 mg / kg of body weight, followed by the FOLFIRI regimen.
This is considered as one treatment cycle. The FOLFIRI regimen to be used is irinotecan 180 mg/m2 intravenous infusion over 90 minutes and folinic acid (dl racemic) 400 mg/m² intravenous infusion over 2 hours at the same time on day 1 using 3 a Y-line, followed by 5-fluorouracil (5-FU) 400 mg / m² intravenous bolus, followed by 5-FU 2400 mg / m² continuous intravenous infusion over 46 hours.
The treatment cycle is repeated every 2 weeks. ZALTRAP treatment should be continued until disease progression or unacceptable toxicity occurs. 4). 5 x 109/L or platelet count is ≥75 x 109 /L. Febrile neutropenia or neutropenic sepsis Irinotecan dose should be reduced by 15-20 % in subsequent cycles.
If recurrence, 5-FU bolus and infusion doses should additionally be reduced by 20 % in subsequent cycles. If recurrence after irinotecan and 5-FU dose reductions, reduction of ZALTRAP dose to 2 mg/kg could be considered. The use of granulocyte colony-stimulating factor (G-CSF) may be considered.
4) The infusion should be temporarily suspended until the reaction resolves. Treatment with corticosteroids and/or antihistamines can be used as clinically indicated. Pre-treatment with corticosteroids and/or antihistamines may be considered in subsequent cycles.
4) ZALTRAP/FOLFIRI should be discontinued and appropriate medical therapy should be administered. 4) ZALTRAP should be temporarily suspended until hypertension is controlled. In case of recurrent medically significant or severe hypertension, despite optimal treatment, ZALTRAP should be suspended until the hypertension is controlled and the dose reduced to 2 mg / kg for subsequent cycles.
4) ZALTRAP should be suspended when proteinuria ≥2 grams per 24 hours and resumed when proteinuria < 2 grams per 24 hours. If recurrence, the treatment should be suspended until <2 grams per 24 hours and then the dose reduces to 2 mg/kg.
FOLFIRI Dose modification when used in combination with ZALTRAP Severe stomatitis and Palmar-Plantar Erythrodysaesthesia syndrome 5-FU bolus should be reduced and the infusion dose reduced by 20 %. Severe diarrhoea Irinotecan dose should be reduced by 15-20 %.
Summary of the safety profile The safety of ZALTRAP in combination with FOLFIRI was evaluated in 1,216 patients previously treated for metastatic colorectal cancer, of which 611 patients were treated with ZALTRAP 4 mg/kg every two weeks (one cycle) and 605 patients were treated with placebo/FOLFIRI in a phase III study.
Patients received a median number of 9 cycles of the ZALTRAP/FOLFIRI regimen. The most common adverse reactions (all grades, ≥ 20 % incidence) reported at least 2 % greater incidence for the ZALTRAP/FOLFIRI regimen as compared to the placebo/FOLFIRI regimen in order of decreasing frequency were leucopenia, diarrhoea, neutropenia, proteinuria, increased aspartate aminotransferase (AST), stomatitis, fatigue, thrombocytopenia, increased alanine aminotransferase (ALT), hypertension, weight loss, decreased appetite, epistaxis, abdominal pain, dysphonia, increased serum creatinine, and headache (see Table 1).
The most common reported grades 3-4 reactions ( ≥5 % incidence) reported at least 2 % greater incidence for the ZALTRAP/FOLFIRI regimen as compared to the placebo/FOLFIRI regimen in order of decreasing frequency, were neutropenia, diarrhoea, hypertension, leucopenia, stomatitis, fatigue, proteinuria, and asthenia (see Table 1).
1 %). Tabulated summary of adverse reactions Adverse reactions and laboratory abnormalities reported in patients treated with the ZALTRAP/FOLFIRI regimen compared to patients treated with the placebo/FOLFIRI regimen are listed in Table 1 according to MedDRA system organ class and frequency categories.
Adverse reactions in Table 1 are defined as either any adverse clinical reaction or laboratory abnormality 10 having ≥ 2 % greater incidence (all grades) in the aflibercept treatment group in comparison to the placebo treatment group in the MCRC study including those that do not meet this threshold but were consistent with the anti-VEGF class and were seen in any study with aflibercept.
8). Patients should be monitored for signs and symptoms of GI bleeding and other severe bleeding. 2). Thrombocytopenia has been reported in patients treated with the ZALTRAP/FOLFIRI regimen. Monitoring of complete blood count (CBC) with platelets is recommended at baseline, prior to initiation of each cycle of aflibercept, and as clinically necessary.
2). 8). Patients should be monitored for signs and symptoms of GI perforation. 2). 8). 2). 8). Pre-existing hypertension must be adequately controlled before starting aflibercept. If hypertension cannot be adequately controlled, treatment with aflibercept should not be initiated.
It is recommended to monitor blood pressure every two weeks, including before each administration or as clinically 6 indicated during treatment with aflibercept. In the event of hypertension on aflibercept treatment, blood pressure should be controlled with appropriate anti-hypertensive therapy and blood pressure should be monitored regularly.
In case of recurrent medically significant or severe hypertension, despite optimal treatment, aflibercept should be suspended until the hypertension is controlled and the aflibercept dose should be reduced to 2 mg/kg for subsequent cycles.
2). Hypertension may exacerbate underlying cardiovascular disease. Caution should be exercised when treating patients with history of clinically significant cardiovascular disease such as coronary artery disease, or congestive heart failure with ZALTRAP.
Patients with NYHA class III or IV congestive heart failure should not be treated with ZALTRAP. Aneurysms and artery dissections The use of VEGF pathway inhibitors in patients with or without hypertension may promote the formation of aneurysms and/or artery dissections.
Before initiating ZALTRAP, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm. Cardiac failure and ejection fraction decreased Cardiac failure and ejection fraction decreased have been reported in patients treated with ZALTRAP.
1. 4). For contraindications related to FOLFIRI components (irinotecan, 5-FU, and folinic acid), refer to the current respective summary of product characteristics.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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If severe diarrhoea recurs on a subsequent cycle, the 5-FU bolus and infusion dose should also be reduced by 20 %. If severe diarrhoea persists with both dose reductions, FOLFIRI should be discontinued. Treatment with anti-diarrhoeal medicinal products and rehydration can be used as needed.
For additional toxicities related to irinotecan, 5-FU, or folinic acid, refer to the current respective summary of product characteristics. 4 % of patients were aged ≥ 75. No dose adjustments of ZALTRAP is required in the elderly people.
2). Clinical data suggest that no change in aflibercept dose is required in patients with mild to moderate hepatic impairment. There are no data regarding the administration of aflibercept in patients with severe hepatic impairment. 2).
Clinical data suggest that no change in starting dose is required in patients with mild to moderate renal impairment. There are very limited data in patients with severe renal impairment; therefore, these patients should be treated with caution.
Paediatric population There is no relevant use of ZALTRAP in the paediatric population for the indication of metastatic colorectal cancer. Method of administration 5 ZALTRAP is to be administered only as an intravenous infusion over 1 hour.
Due to hyperosmolality (1000 mOsmol/kg) of the ZALTRAP concentrate, undiluted ZALTRAP concentrate must not be administered as an intravenous push or bolus. 4). Each vial of concentrate for solution for infusion is for single use (single-dose) only.
Precautions to be taken before handling or administering the medicinal product For instructions on dilution of the medicinal product before administration, and on infusion […]
0 (grade ≥ 3 = G ≥ 3). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Frequencies are based on all grades and defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).
0 (1) See “Description of selected adverse reactions” in this section (2) Based on laboratory values (percentages done on patients with laboratory assessments) (3) Compilation of clinical and laboratory data (4) Not reported in MCRC study; however, PRES was reported in patients from other studies treated with aflibercept as monotherapy and in combination with […]
Baseline and periodic evaluations of left ventricular function should be considered while the patient is receiving Zaltrap. Patients should be monitored for signs and symptoms of cardiac failure and ejection fraction decreased. Discontinue ZALTRAP in patients who experience cardiac failure and ejection fraction decreased.
8). 2). 8). 2). Patients with Grade 3 DVT should be treated with anticoagulation as clinically indicated, and aflibercept therapy should be continued. In the event of recurrence, despite appropriate anticoagulation, aflibercept treatment should be discontinued.
Patients with thromboembolic events of Grade 3 or lower need to be closely monitored. 8). Proteinuria should be monitored by urine dipstick analysis and/or urinary protein creatinine ratio (UPCR) for the development or worsening of proteinuria before each aflibercept administration.
Patients with a dipstick of ≥ 2+ for protein or a UPCR > 1 or a protein/creatinine ratio (PCR)> 100 mg/mmol should undergo a 24-hour urine collection. Aflibercept administration should be suspended for ≥ 2 grams of proteinuria/24 hours and restarted when proteinuria is <2 grams/24 hours.
If there is recurrence, the administration should be suspended 7 until <2 grams/24 hours and then the dose reduced to 2 mg/kg. 2). 8). Monitoring of complete blood count (CBC) with differential count is recommended at baseline and prior to initiation of each cycle of […]