Zaltrap

Zaltrap Special Precautions

aflibercept

Manufacturer:

sanofi-aventis

Distributor:

DKSH
Full Prescribing Info
Special Precautions
Haemorrhage: An increased risk of haemorrhage, including severe and sometimes fatal haemorrhagic events has been reported in patients treated with aflibercept (see Adverse Reactions).
Patients should be monitored for signs and symptoms of GI bleeding and other severe bleeding.Aflibercept should not be administered to patients with severe haemorrhage (see Dosage & Administration).
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. Administration of the ZALTRAP/FOLFIRI should be delayed until platelet count is ≥ 75 x 109/L (see Dosage & Administration).
Gastrointestinal Perforation: GI perforation including fatal GI perforation has been reported in patients treated with aflibercept (see Adverse Reactions).
Patients should be monitored for signs and symptoms of GI perforation. Aflibercept treatment should be discontinued in patients who experience GI perforation (see Dosage & Administration).
Fistula Formation: Fistula formation involving GI and non-GI sites has occurred in patients treated with aflibercept (see Adverse Reactions).
Aflibercept treatment should be discontinued in patients who develop fistula (see Dosage & Administration).
Hypertension: An increased risk of grade 3 - 4 hypertension (including hypertension and one case of essential hypertension) has been observed in patients treated with the ZALTRAP/FOLFIRI regimen (see Adverse Reactions).
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 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. Aflibercept should be permanently discontinued if hypertension cannot be adequately managed with appropriate anti-hypertensive therapy or aflibercept dose reduction, or if hypertensive crisis or hypertensive encephalopathy occurs (see Dosage & Administration).
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.
Cardiac Failure and Ejection Fraction Decreased: Cardiac failure and ejection fraction decreased have been reported in patients treated with 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.
Thrombotic and Embolic Events: Arterial Thromboembolic Events (ATE): ATE (including transient ischaemic attack, cerebrovascular accident, angina pectoris, intracardiac thrombus, myocardial infarction, arterial embolism, and ischaemic colitis) have been observed in patients treated with aflibercept (see Adverse Reactions).
Aflibercept treatment should be discontinued in patients who experience an ATE (see Dosage & Administration).
Venous Thromboembolic Events (VTE): VTE including deep vein thrombosis (DVT) and pulmonary embolism (infrequently fatal) have been reported in patients treated with aflibercept (see Adverse Reactions).
ZALTRAP should be discontinued in patients with life-threatening (Grade 4) thromboembolic events (including pulmonary embolism) (see Dosage & Administration). 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.
Proteinuria: Severe proteinuria, nephrotic syndrome, and thrombotic microangiopathy (TMA) have been observed in patients treated with aflibercept (see Adverse Reactions).
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 until < 2 grams/24 hours and then the dose reduced to 2 mg/kg. Aflibercept treatment should be discontinued in patients who develop nephrotic syndrome or TMA (see Dosage & Administration).
Neutropenia and Neutropenic Complications: A higher incidence of neutropenic complications (febrile neutropenia and neutropenic infection) has been observed in patients treated with the ZALTRAP/FOLFIRI regimen (see Adverse Reactions).
Monitoring of complete blood count (CBC) with differential count is recommended at baseline and prior to initiation of each cycle of aflibercept. Administration of ZALTRAP/FOLFIRI should be delayed until neutrophil count is ≥ 1.5 x 109/L (see Dosage & Administration). Therapeutic use of G-CSF at first occurrence of grade ≥ 3 neutropenia and secondary prophylaxis may be considered in patients who may be at increased risk for neutropenia complications.
Diarrhoea and Dehydration: A higher incidence of severe diarrhoea has been observed in patients treated with the ZALTRAP/FOLFIRI regimen (see Adverse Reactions).
Dose modification of FOLFIRI regimen (see Dosage & Administration), anti-diarrhoeal medicinal products, and rehydration as needed should be instituted.
Hypersensitivity Reactions: In the pivotal study of MCRC patients, severe hypersensitivity reactions have been reported in patients treated with the ZALTRAP/FOLFIRI regimen (see Adverse Reactions).
In the event of a severe hypersensitivity reaction (including bronchospasm, dyspnoea, angioedema, and anaphylaxis), aflibercept should be discontinued and appropriate medical measures should be administered (see Dosage & Administration).
In the event of a mild to moderate hypersensitivity reaction to ZALTRAP (including flushing, rash, urticaria, and pruritus), aflibercept should be temporarily suspended until the reaction is resolved. Treatment with corticosteroids and/or antihistamines can be initiated as clinically indicated. Pre-treatment with corticosteroids and/or antihistamines may be considered in subsequent cycles (see Dosage & Administration). Caution should be used when retreating patients with prior hypersensitivity reactions as recurrent hypersensitivity reactions have been observed in some patients despite prophylaxis, including corticosteroids.
Compromised Wound Healing: Aflibercept impaired wound healing in animal models (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).
Potential for compromised wound healing (wound dehiscence, anastomotic leakage) has been reported with aflibercept (see Adverse Reactions).
Aflibercept should be suspended for at least 4 weeks prior to elective surgery.
It is recommended that aflibercept not be initiated for at least 4 weeks following major surgery and not until the surgical wound is fully healed. For minor surgery such as central venous access port placement, biopsy, and tooth extraction, aflibercept may be initiated/restarted once the surgical wound is fully healed. Aflibercept should be discontinued in patients with compromised wound healing requiring medical intervention (see Dosage & Administration).
Osteonecrosis of the Jaw (ONJ): Cases of ONJ have been reported in cancer patients treated with Zaltrap, several of whom had received prior or concomitant treatment with intravenous bisphosphonates, for which ONJ is an identified risk. Caution should be exercised when Zaltrap and intravenous bisphosphonates are administered concurrently or sequentially. Invasive dental procedures are also an identified risk factor. A dental examination and appropriate preventive dentistry should be considered prior to starting the treatment with Zaltrap. Invasive dental procedures should, if possible, be avoided in patients treated with Zaltrap and who have previously received or are receiving intravenous bisphosphonates (see Adverse Reactions).
Posterior Reversible Encephalopathy Syndrome (PRES): PRES was not reported in the pivotal phase III study of MCRC patients. In other studies, PRES was reported in patients treated with aflibercept as monotherapy and in combination with other chemotherapies (see Adverse Reactions).
PRES may present with altered mental status, seizure, nausea, vomiting, headache, or visual disturbances. The diagnosis of PRES is confirmed by brain Magnetic Resonance Imaging (MRI).
Aflibercept should be discontinued in patients that develop PRES (see Dosage & Administration).
Performance Status and Co-morbidities: Patients with ECOG performance status ≥ 2 or having significant co-morbidities may be at greater risk for a poor clinical outcome and should be carefully monitored for early clinical deterioration.
Off-label Intravitreal Use: ZALTRAP is a hyperosmotic solution, which is not formulated for compatibility with the intraocular environment. ZALTRAP must not be administered as an intravitreal injection (see Contraindications).
Effects on Ability to Drive and Use Machines: ZALTRAP has no or negligible influence on the ability to drive and use machines. If patients are experiencing symptoms that affect their vision or concentration, or their ability to react, they should be advised not to drive or use machines (see Adverse Reactions).
Renal Impairment: There are very limited data available for patients with severe renal impairment treated with aflibercept. No dose adjustment is required for aflibercept (see Pharmacology: Pharmacokinetics under Actions, Dosage & Administration and Adverse Reactions).
Use in Elderly: Older people patients ≥ 65 years had an increased risk of diarrhoea, dizziness, asthenia, weight loss and dehydration. Careful monitoring is recommended in order to rapidly detect and treat signs and symptoms of diarrhoea and dehydration and to minimize potential risk (see Adverse Reactions).
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