ZALTRAP CONCENTRATE FOR SOLUTION FOR INFUSION 25 MG/ML [SIN14592P]

Product Info

ZALTRAP CONCENTRATE FOR SOLUTION FOR INFUSION 25 MG/ML

[SIN14592P]

Therapeutic Indications
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.

Posology and Method of Administration
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 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.

Dose Modification
ZALTRAP should be discontinued for (see section Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information):

• Severe haemorrhage

• Gastrointestinal (GI) perforation

• Fistula formation

• Hypertension that is not adequately controlled with anti-hypertensive therapy or occurrence of hypertensive crisis or hypertensive encephalopathy

• Cardiac failure and ejection fraction decreased

• Arterial thromboembolic events (ATE)

• Grade 4 venous thromboembolic events (including pulmonary embolism)

• Nephrotic syndrome or thrombotic microangiopathy (TMA)

• Severe hypersensitivity reactions (including bronchospasm, dyspnoea, angioedema, and anaphylaxis) (see sections Contraindications and Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• Compromised wound healing requiring medical intervention

• Posterior reversible encephalopathy syndrome (PRES) (also known as reversible posterior leukoencephalopathy syndrome (RPLS))

ZALTRAP should be temporarily suspended for at least 4 weeks prior to elective surgery (see section Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

For additional toxicities related to irinotecan, 5-FU, or folinic acid, refer to the current respective summary of product characteristics.

Special Populations

Elderly
In the pivotal MCRC study, 28.2% of patients were aged ≥ 65 and < 75 and 5.4% of patients were aged ≥ 75. No dose adjustments of ZALTRAP is required in the elderly.

Hepatic Impairment
There have been no formal studies with ZALTRAP in patients with hepatic impairment (see section Pharmacokinetic Properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). 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.

Renal Impairment
There have been no formal studies with ZALTRAP in patients with renal impairment (see section Pharmacokinetic Properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). 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
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. ZALTRAP must not be administered as an intravitreal injection (see sections Contraindications and Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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, see section Special Precautions for Disposal and Other Handling – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Contraindications
Hypersensitivity to aflibercept or to any of the excipients listed in section List of Excipients – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Ophthalmic / intravitreal use due to hyperosmotic properties of ZALTRAP (see section Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

For contraindications related to FOLFIRI components (irinotecan, 5-FU, and folinic acid), refer to the current respective summary of product characteristics.