Please wait while the formulary information is being retrieved.
Drug overview for ZALTRAP (aflibercept):
Generic name: AFLIBERCEPT (a-FLIB-er-sept)
Drug class: Antineoplastic-VEGF-A and B,PlGF Growth Factor Inhibitor
Therapeutic class: Antineoplastics
Ziv-aflibercept, a recombinant humanized fusion protein, is a vascular endothelial growth factor A (VEGF-A), VEGF-B, and placental growth factor (PlGF) antagonist that is used as an antineoplastic agent. The IV preparation of Zaltrap(R) (ziv-aflibercept) for use in the treatment of metatastic colorectal cancer contains the same drug as the intravitreal preparation of Eylea(R) (aflibercept), which is used in the treatment of macular degeneration. Because of the potential for medication errors, the US Food and Drug Administration (FDA) required the addition of a prefix to the nonproprietary (generic) name; FDA later approved the addition of the prefix ''ziv'' to the generic name of Zaltrap(R) (ziv-aflibercept) for the US market.
No enhanced Uses information available for this drug.
Generic name: AFLIBERCEPT (a-FLIB-er-sept)
Drug class: Antineoplastic-VEGF-A and B,PlGF Growth Factor Inhibitor
Therapeutic class: Antineoplastics
Ziv-aflibercept, a recombinant humanized fusion protein, is a vascular endothelial growth factor A (VEGF-A), VEGF-B, and placental growth factor (PlGF) antagonist that is used as an antineoplastic agent. The IV preparation of Zaltrap(R) (ziv-aflibercept) for use in the treatment of metatastic colorectal cancer contains the same drug as the intravitreal preparation of Eylea(R) (aflibercept), which is used in the treatment of macular degeneration. Because of the potential for medication errors, the US Food and Drug Administration (FDA) required the addition of a prefix to the nonproprietary (generic) name; FDA later approved the addition of the prefix ''ziv'' to the generic name of Zaltrap(R) (ziv-aflibercept) for the US market.
No enhanced Uses information available for this drug.
DRUG IMAGES
ZALTRAP 200 MG/8 ML VIAL
ZALTRAP 100 MG/4 ML VIAL
The following indications for ZALTRAP (aflibercept) have been approved by the FDA:
Indications:
Metastatic colorectal cancer
Professional Synonyms:
None.
Indications:
Metastatic colorectal cancer
Professional Synonyms:
None.
The following dosing information is available for ZALTRAP (aflibercept):
If toxicities occur, temporary or permanent discontinuance of ziv-aflibercept may be required based on causality.
Ziv-aflibercept should be discontinued in patients who develop severe hemorrhage, GI perforation, compromised wound healing, fistula formation, hypertensive crisis or hypertensive encephalopathy, arterial thromboembolic events, nephrotic syndrome or thrombotic microangiopathy, or reversible posterior leukoencephalopathy syndrome (RPLS). (See Cautions: Warnings/Precautions.)
Ziv-aflibercept therapy should be temporarily suspended at least 4 weeks prior to elective surgery. Therapy also should be temporarily interrupted in patients who develop recurrent or severe hypertension or proteinuria. (See Hypertension and also Proteinuria under Dosage: Dosage Modification for Toxicity, in Dosage and Administration.) Ziv-aflibercept therapy should be delayed in patients with a neutrophil count of less than 1500/mm3. (See Neutropenia and Neutropenic Complications under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
Ziv-aflibercept should be discontinued in patients who develop severe hemorrhage, GI perforation, compromised wound healing, fistula formation, hypertensive crisis or hypertensive encephalopathy, arterial thromboembolic events, nephrotic syndrome or thrombotic microangiopathy, or reversible posterior leukoencephalopathy syndrome (RPLS). (See Cautions: Warnings/Precautions.)
Ziv-aflibercept therapy should be temporarily suspended at least 4 weeks prior to elective surgery. Therapy also should be temporarily interrupted in patients who develop recurrent or severe hypertension or proteinuria. (See Hypertension and also Proteinuria under Dosage: Dosage Modification for Toxicity, in Dosage and Administration.) Ziv-aflibercept therapy should be delayed in patients with a neutrophil count of less than 1500/mm3. (See Neutropenia and Neutropenic Complications under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
No enhanced Administration information available for this drug.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| ZALTRAP 100 MG/4 ML VIAL | Maintenance | Adults infuse 4 mg/kg over 60 minute(s) by intravenous route every 2 weeks |
| ZALTRAP 200 MG/8 ML VIAL | Maintenance | Adults infuse 4 mg/kg over 60 minute(s) by intravenous route every 2 weeks |
No generic dosing information available.
The following drug interaction information is available for ZALTRAP (aflibercept):
There are 0 contraindications.
There are 3 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Deferiprone/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1) CLINICAL EFFECTS: Concurrent use of deferiprone and myelosuppressive agents may result in severe neutropenia or agranulocytosis, which may be fatal. PREDISPOSING FACTORS: Agranulocytosis may be less common in patients receiving deferiprone for thalassemia, and more common in patients treated for other systemic iron overload conditions (e.g. myelodysplastic syndromes, sickle cell disease).(2,3) Inadequate monitoring appears to increase the risk for severe outcomes. Manufacturer post market surveillance found that in all fatal cases of agranulocytosis reported between 1999 and 2005, data on weekly white blood count (WBC) monitoring was missing. In three fatal cases, deferiprone was continued for two to seven days after the detection of neutropenia or agranulocytosis.(2) PATIENT MANAGEMENT: If possible, discontinue one of the drugs associated with risk for neutropenia or agranulocytosis. If alternative therapy is not available, documentation and adherence to the deferiprone monitoring protocol is essential. Baseline absolute neutrophil count (ANC) must be at least 1,500/uL prior to starting deferiprone. Monitor ANC weekly during therapy. If infection develops, interrupt deferiprone therapy and monitor ANC more frequently. If ANC is less than 1,500/uL but greater than 500/uL, discontinue deferiprone and any other drugs possibly associated with neutropenia. Initiate ANC and platelet counts daily until recovery (i.e. ANC at least 1,500/uL). If ANC is less than 500/uL, discontinue deferiprone, evaluate patient and hospitalize if appropriate. Do not resume deferiprone unless potential benefits outweigh potential risks.(1) DISCUSSION: Drugs linked to this monograph have an FDA Boxed Warning for risk of neutropenia, agranulocytosis, or pancytopenia, or have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(1-25) In pooled clinical studies submitted to the FDA, 6.1% of deferiprone patients met criteria for neutropenia and 1.7% of patients developed agranulocytosis.(1) The time to onset of agranulocytosis was highly variable with a range of 65 days to 9.2 years (median, 161 days).(3) |
DEFERIPRONE, DEFERIPRONE (3 TIMES A DAY), FERRIPROX, FERRIPROX (2 TIMES A DAY), FERRIPROX (3 TIMES A DAY) |
| Clozapine/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine and other myelosuppressive agents may be associated with neutropenia or agranulocytosis.(2) CLINICAL EFFECTS: Moderate neutropenia, even if due to combination therapy, may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder (e.g. schizophrenia). The disease treated by the myelosuppressive agent may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of the myelosuppressive agent. Undetected severe neutropenia or agranulocytosis may be fatal. PREDISPOSING FACTORS: Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia. PATIENT MANAGEMENT: If a patient stabilized on clozapine therapy requires treatment with a myelosuppressive agent, the clozapine prescriber should consult with prescriber of the myelosuppressive agent (e.g. oncologist) to discuss treatment and monitoring options.(2) More frequent ANC monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. Clozapine is only available through a restricted distribution system which requires documentation of the absolute neutrophil count (ANC) prior to dispensing.(1-2) For most clozapine patients, clozapine treatment must be interrupted for a suspected clozapine-induced ANC < 1000 cells/microliter. For patients with benign ethnic neutropenia (BEN), treatment must be interrupted for suspected clozapine-induced neutropenia < 500 cells/microliter.(2) DISCUSSION: Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing.(1) Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(3-26) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
| Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1) |
HICON, SODIUM IODIDE I-131 |
There are 0 moderate interactions.
The following contraindication information is available for ZALTRAP (aflibercept):
Drug contraindication overview.
The manufacturer states there are no known contraindications to the use of ziv-aflibercept.
The manufacturer states there are no known contraindications to the use of ziv-aflibercept.
There are 8 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Acute arterial thromboembolism |
| Gastrointestinal perforation |
| Hypertensive crisis |
| Lactation |
| Nephrotic syndrome |
| Posterior reversible encephalopathy syndrome |
| Thrombotic thrombocytopenic purpura |
| Transient cerebral ischemia |
There are 14 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Angina |
| Gastrointestinal fistula |
| Hemorrhage |
| Hypertension |
| Impaired wound healing |
| Invasive surgical procedure |
| Neutropenic disorder |
| New fistula formation involving an internal organ |
| Pregnancy |
| Proteinuria |
| Severe diarrhea |
| Severe infection |
| Stomatitis |
| Thrombocytopenic disorder |
There are 0 moderate contraindications.
The following adverse reaction information is available for ZALTRAP (aflibercept):
Adverse reaction overview.
The most common adverse effects reported in 20% or more of patients receiving ziv-aflibercept in combination with FOLFIRI and at an incidence that is at least 2% higher than that reported with placebo in combination with FOLFIRI include leukopenia, diarrhea, neutropenia, proteinuria, elevated aminotransferase (i.e., AST, ALT) concentrations, stomatitis, fatigue, thrombocytopenia, hypertension, weight loss, decreased appetite, epistaxis, abdominal pain, dysphonia, elevated serum creatinine concentration, and headache. The most common grade 3 or 4 adverse effects reported in 5% or more of patients receiving ziv-aflibercept in combination with FOLFIRI and at an incidence that is at least 2% higher than that reported with placebo in combination with FOLFIRI include neutropenia, diarrhea, hypertension, leukopenia, stomatitis, fatigue, proteinuria, and asthenia.
The most common adverse effects reported in 20% or more of patients receiving ziv-aflibercept in combination with FOLFIRI and at an incidence that is at least 2% higher than that reported with placebo in combination with FOLFIRI include leukopenia, diarrhea, neutropenia, proteinuria, elevated aminotransferase (i.e., AST, ALT) concentrations, stomatitis, fatigue, thrombocytopenia, hypertension, weight loss, decreased appetite, epistaxis, abdominal pain, dysphonia, elevated serum creatinine concentration, and headache. The most common grade 3 or 4 adverse effects reported in 5% or more of patients receiving ziv-aflibercept in combination with FOLFIRI and at an incidence that is at least 2% higher than that reported with placebo in combination with FOLFIRI include neutropenia, diarrhea, hypertension, leukopenia, stomatitis, fatigue, proteinuria, and asthenia.
There are 33 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Hemorrhage Hypertension Increased alanine transaminase Increased aspartate transaminase Leukopenia Neutropenic disorder Palmar-plantar erythrodysesthesia Severe diarrhea Thrombocytopenic disorder |
Angina Dehydration Gastrointestinal hemorrhage Hematuria Kidney disease with reduction in glomerular filtration rate (GFr) Pneumonia Rectal bleeding Thromboembolic disorder Transient cerebral ischemia |
| Rare/Very Rare |
|---|
|
Acute arterial thromboembolism Aortic aneurysm with dissection Arterial aneurysm Arterial dissection Aseptic necrosis of jaw bone Cerebrovascular accident Gastrointestinal fistula Gastrointestinal perforation Heart failure Impaired wound healing Intracranial bleeding Nephrotic syndrome Posterior reversible encephalopathy syndrome Pulmonary hemorrhage Thrombotic thrombocytopenic purpura |
There are 21 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Diarrhea Dyspnea Epistaxis Fatigue General weakness Headache disorder Proteinuria Stomatitis Voice change Weight loss |
Anorexia Dyschromia Hemorrhoids Rectal pain Rhinorrhea Skin pigmentation enhancement Sore throat Tooth disorder Upper respiratory infection Urinary tract infection |
| Rare/Very Rare |
|---|
| None. |
The following precautions are available for ZALTRAP (aflibercept):
Safety and efficacy of ziv-aflibercept have not been established in pediatric patients younger than 18 years of age.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Category C. (See Users Guide.) (See Advice to Patients.)
It is not known whether ziv-aflibercept is distributed into milk in humans. Because of the potential for serious adverse reactions to ziv-aflibercept in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
In the VELOUR study, 34% of patients were 65 years of age or older and 5% were 75 years of age or older. Although no overall differences in efficacy (i.e., overall survival) were observed between geriatric and younger patients, the incidences of diarrhea, dizziness, asthenia, weight loss, and dehydration were higher among patients 65 years of age or older compared with younger patients. Geriatric patients should be monitored more closely for diarrhea and dehydration.
(See Diarrhea and Dehydration under Warnings/Precautions: Other Warnings and Precautions, in Cautions.) Dosage adjustment is not required in patients 65 years of age or older.
(See Diarrhea and Dehydration under Warnings/Precautions: Other Warnings and Precautions, in Cautions.) Dosage adjustment is not required in patients 65 years of age or older.
The following prioritized warning is available for ZALTRAP (aflibercept):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for ZALTRAP (aflibercept)'s list of indications:
| Metastatic colorectal cancer | |
| C18 | Malignant neoplasm of colon |
| C18.0 | Malignant neoplasm of cecum |
| C18.1 | Malignant neoplasm of appendix |
| C18.2 | Malignant neoplasm of ascending colon |
| C18.3 | Malignant neoplasm of hepatic flexure |
| C18.4 | Malignant neoplasm of transverse colon |
| C18.5 | Malignant neoplasm of splenic flexure |
| C18.6 | Malignant neoplasm of descending colon |
| C18.7 | Malignant neoplasm of sigmoid colon |
| C18.8 | Malignant neoplasm of overlapping sites of colon |
| C18.9 | Malignant neoplasm of colon, unspecified |
| C19 | Malignant neoplasm of rectosigmoid junction |
| C20 | Malignant neoplasm of rectum |
| C21.8 | Malignant neoplasm of overlapping sites of rectum, anus and anal canal |
Formulary Reference Tool