ZALTRAP- ziv-aflibercept solution, concentrate

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

AFLIBERCEPT (UNII: 15C2VL427D) (AFLIBERCEPT - UNII:15C2VL427D)

Available from:

sanofi-aventis U.S. LLC

INN (International Name):

aflibercept

Composition:

aflibercept 100 mg in 4 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

ZALTRAP, in combination with fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. None. Risk Summary Based on findings from animal reproduction studies and its mechanism of action [see Clinical Pharmacology (12.1)] , ZALTRAP can cause fetal harm when administered to pregnant women. There is insufficient data in pregnant women exposed to ZALTRAP to assess the risks. Administration of ziv-aflibercept during the period of organogenesis was embryotoxic and teratogenic in rabbits at exposure levels approximately 0.3 times the human exposure at the 4 mg per kg dose (see Data) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data In pregnant rabbits, administration of ziv-aflibercept during the period of organogenesis resulted in an increase in postimplantation loss and external (including anasarca, umbilical hernia, diaphragmatic hernia and gastroschisis, cleft palate, ectrodactyly, and anal atresia), visceral (heart, great vessels, and arteries), and skeletal fetal malformations (including fused vertebrae, sternebrae, and ribs, supernumerary arches and ribs, and incomplete ossification) at doses greater than or equal to 3 mg per kg, administered once every 3 days (approximately 0.3 times the human exposure at the 4 mg per kg dose based on AUC). Risk Summary There are no data on the presence of ziv-aflibercept in human milk, or the effects of ziv-aflibercept on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with ZALTRAP and for 1 month following the last dose. ZALTRAP can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify the pregnancy status in females of reproductive potential prior to initiating ZALTRAP [see Use in Specific Populations (8.1)] . Contraception Females Based on data from animal studies and its mechanism of action, ZALTRAP can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)] . Advise female patients of reproductive potential to use effective contraception during treatment with ZALTRAP and for 3 months following the last dose. Infertility Advise female and male patients of reproductive potential that ZALTRAP may impair reproductive function and fertility [see Nonclinical Toxicology (13.1)] . The safety and effectiveness in pediatric patients have not been established. Safety and efficacy were assessed, but not established in a dose-escalation, safety, and tolerability study (NCT00622414) in 21 patients with solid tumors 2 to 21 years of age (median age 12.9). The mean elimination half-life of free ziv-aflibercept determined after the first dose in 8 pediatric patients aged 5 to 17 years was within the range of values previously observed in adults. The maximum tolerated dose based on body weight in these pediatric patients was lower than the dose known to be safe and effective in adults with mCRC. Juvenile Animal Toxicity Data Weekly/every-two-weeks intravenous administration of ziv-aflibercept at dose of 3 mg per kg (approximately 0.6 times the human exposure at the 4 mg per kg dose based on AUC) to growing young adult (sexually mature) cynomolgus monkeys for up to 6 months resulted in changes in the bone (effects on growth plate and the axial and appendicular skeleton), nasal cavity (atrophy/loss of the septum and/or turbinates), kidney (glomerulopathy with inflammation), ovary (decreased number of maturing follicles, granulosa cells, and/or theca cells), and adrenal gland (decreased vacuolation with inflammation). In another study in sexually immature cynomolgus monkeys (treated intravenously for 3 months), there were similar effects. The skeletal and nasal cavity effects were not reversible after a post-dosing recovery period. Of the 611 patients with mCRC, patients treated with ZALTRAP/FOLFIRI, 205 (34%) were 65 years or older, and 33 (5%) were 75 years or older. Elderly patients (≥65 years of age) experienced higher incidences (≥5%) of diarrhea, dizziness, asthenia, weight decrease, and dehydration when compared to younger patients. Monitor elderly patients more closely for diarrhea and dehydration [see Warnings and Precautions (5.9)]. The effect of ZALTRAP on overall survival was similar in patients <65 years old and ≥65 years old who received ZALTRAP/FOLFIRI. No dosage modification is recommended for patients with renal impairment [see Clinical Pharmacology (12.3)] . No dosage modification is recommended for patients with mild (total bilirubin >1 to 1.5 times upper limit normal [ULN] and any aspartate transaminase [AST]) and moderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment [see Clinical Pharmacology (12.3)] . ZALTRAP has not been studied in patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).

Product summary:

ZALTRAP (ziv-aflibercept) injection is a clear, colorless to pale-yellow solution supplied in single-dose vials with a concentration of 25 mg/mL. NDC 0024-5840-01: carton containing one single-dose vial of 100 mg/4 mL (25 mg/mL) NDC 0024-5841-01: carton containing one single-dose vial of 200 mg/8 mL (25 mg/mL) Store ZALTRAP vials in a refrigerator at 2°C to 8°C (36°F to 46°F). Keep the vials in the original outer carton to protect from light. Discard unused portion.

Authorization status:

Biologic Licensing Application

Summary of Product characteristics

ZALTRAP- ZIV-AFLIBERCEPT SOLUTION, CONCENTRATE
SANOFI-AVENTIS U.S. LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ZALTRAP SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR ZALTRAP.
ZALTRAP (ZIV-AFLIBERCEPT) INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2012
RECENT MAJOR CHANGES
Warnings and Precautions (5.11)
12/2023
INDICATIONS AND USAGE
ZALTRAP, a vascular endothelial growth factor inhibitor, in
combination with fluorouracil, leucovorin,
irinotecan (FOLFIRI), is indicated for the treatment of patients with
metastatic colorectal cancer that is
resistant to or has progressed following an oxaliplatin-containing
regimen. (1)
DOSAGE AND ADMINISTRATION
4 mg per kg as an intravenous infusion over 1 hour every 2 weeks.
(2.1, 2.3)
Do not administer as an intravenous push or bolus. (2.3)
DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/4 mL (25 mg/mL) and 200 mg/8 mL (25 mg/mL) solution
in a single-dose vial (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
Hemorrhage: Severe and sometimes fatal hemorrhage, including
gastrointestinal (GI) hemorrhage, has
been reported in patients who have received ZALTRAP. Do not administer
ZALTRAP to patients with
severe hemorrhage. (5.1)
Gastrointestinal Perforation: Discontinue ZALTRAP therapy in patients
who experience GI perforation.
(5.2)
Impaired Wound Healing: Withhold ZALTRAP for at least 4 weeks prior to
elective surgery. Do not
administer for at least 4 weeks following major surgery and until
wounds have adequately healed.
Discontinue ZALTRAP in patients with impaired wound healing. The
safety of resumption of ZALTRAP
after resolution of wound healing complications has not been
established. (5.3)
Fistula Formation: Discontinue ZALTRAP if fistula occurs. (2.2, 5.4)
Hypertension: Monitor blood pressure and treat hypertension.
Temporarily suspend ZALTRAP if
hypertension is not controlled. Discontinue ZALTRAP if hypertensive
crisis develops. (2.2, 5.5)
Arterial Thromboembolic Events (ATE):