ERBITUX Solution for infusion Ref.[6649] Active ingredients: Cetuximab

Erbitux must be administered under the supervision of a physician experienced in the use of antineoplastic medicinal products. Close monitoring is required during the infusion and for at least 1 hour after the end of the infusion. Availability of resuscitation equipment must be ensured.

Posology

Prior to the first infusion, patients must receive premedication with an antihistamine and a corticosteroid at least 1 hour prior to administration of cetuximab. This premedication is recommended prior to all subsequent infusions.

Colorectal cancer

RAS wild-type metastatic colorectal cancer

In patients with RAS wild-type metastatic colorectal cancer, cetuximab is used in combination with chemotherapy or as a single agent (see section 5.1). Evidence of wild-type RAS (KRAS and NRAS) status is required before initiating treatment with Erbitux. Mutational status should be determined by an experienced laboratory using validated test methods for detection of KRAS and NRAS (exons 2, 3, and 4) mutations (see section 4.4 and 5.1).

Erbitux may be administered in a weekly or every other week dose regimen.

Weekly dose regimen:

Erbitux is administered once a week. The initial dose is 400 mg cetuximab per m² body surface area (BSA). All subsequent weekly doses are 250 mg/m² each.

Biweekly dose regimen:

Erbitux is administered once every other week. Each dose is 500 mg cetuximab per m² body surface area.

BRAF V600E mutant metastatic colorectal cancer

In patients with BRAF V600E mutant metastatic colorectal cancer, cetuximab is used in combination with encorafenib and FOLFOX or encorafenib (see section 5.1). Evidence of BRAF V600E mutation status is required before initiating treatment with Erbitux. Mutational status should be assessed by a CE marked IVD with the corresponding intended purpose. If the CE-marked IVD is not available, an alternative validated test should be used.

In combination with encorafenib in patients who received prior systemic therapy:

Erbitux is administered once a week. The very first dose is 400 mg cetuximab per m² body surface area (BSA). All subsequent weekly doses are 250 mg/m² each.

In combination with encorafenib and FOLFOX:

Erbitux is administered once every other week. Each dose is 500 mg cetuximab per m² body surface area.

For the dosage or recommended dose modifications of concomitantly used chemotherapeutic agents and encorafenib, refer to the product information for these medicinal products. Chemotherapeutic agents must not be administered earlier than 1 hour after the end of the cetuximab infusion. Encorafenib should be administered before starting cetuximab infusion.

It is recommended that cetuximab treatment be continued until progression of the underlying disease.

Squamous cell cancer of the head and neck

In combination with radiation therapy

In patients with locally advanced squamous cell cancer of the head and neck, cetuximab is used concomitantly with radiation therapy. It is recommended to start cetuximab therapy one week before radiation therapy and to continue cetuximab therapy until the end of the radiation therapy period.

Erbitux is administered once a week. The initial dose is 400 mg cetuximab per m² body surface area (BSA). All subsequent weekly doses are 250 mg/m² each.

In combination with platinum-based chemotherapy

In patients with recurrent and/or metastatic squamous cell cancer of the head and neck, cetuximab is used in combination with platinum-based chemotherapy followed by cetuximab as maintenance therapy until disease progression (see section 5.1). Chemotherapy must not be administered earlier than 1 hour after the end of the cetuximab infusion.

Erbitux may be administered in a weekly or every other week dose regimen.

Weekly dose regimen:

Erbitux is administered once a week. The initial dose is 400 mg cetuximab per m² body surface area (BSA). All subsequent weekly doses are 250 mg/m² each.

Biweekly dose regimen:

Erbitux is administered once every other week. Each dose is 500 mg cetuximab per m² body surface area.

Special populations

Cetuximab has not been studied in patients with pre-existing haematological disorders (see section 4.4).

No dose adjustment is required in older people, but the experience is limited in patients 75 years of age and above.

Patients with mild (CRCL ≥60 and <90 mL/min) and moderate (CRCL ≥30 and <60 mL/min) renal impairment, as well as mild hepatic impairment according to National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria, have been investigated to date. The effect of moderate or severe hepatic impairment, as defined by NCI-ODWG criteria, on cetuximab pharmacokinetics has not been assessed. The pharmacokinetics of cetuximab in patients with severe (CRCL ≥15 and <30 mL/min) renal impairment or end-stage renal disease have not been evaluated. See section 5.2.

Paediatric population

There is no relevant use of cetuximab in the paediatric population for the granted indications.

Method of administration

Erbitux 5 mg/mL is administered intravenously with an infusion pump, gravity drip or a syringe pump (for handling instructions, see section 6.6).

The initial dose should be given slowly to minimize risk of infusion related reactions (see section 4.4). The recommended infusion period is 120 minutes. For subsequent cetuximab administration the infusion rate must not exceed 10 mg/min. If initial infusion is well tolerated the recommended infusion period for weekly dose regimen of 250 mg/m² is 60 minutes and recommended infusion period for biweekly dose regimen of 500 mg/m² is 120 minutes.

There is limited experience with weekly administrations of doses higher than 250 mg/m² body surface area or biweekly administrations of doses higher than 500 mg/m² body surface area. In clinical studies with doses up to 700 mg/m² given every 2 weeks the safety profile was consistent with that described in section 4.8.

4 years.

Chemical and physical in-use stability of Erbitux 5 mg/mL has been demonstrated for 48 hours at 25°C, if the solution is prepared as described in section 6.6.

Erbitux does not contain any antimicrobial preservative or bacteriostatic agent. From a microbiological point of view, the product shall be used immediately after opening. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless opening has taken place in controlled and validated aseptic conditions.

Store in a refrigerator (2°C–8°C).

For storage conditions after opening, see section 6.3.

20 mL or 100 mL of solution in a vial (Type I glass) with a stopper (halobutyl rubber) and a seal (aluminium/polypropylen).

Pack size of 1 vial.

Not all vial sizes may be marketed.

Erbitux may be administered via a gravity drip, an infusion pump or a syringe pump. A separate infusion line must be used for the infusion, and the line must be flushed with sterile sodium chloride 9 mg/mL (0.9%) solution for injection at the end of infusion.

Erbitux 5 mg/mL is compatible:

• with polyethylene (PE), ethyl vinyl acetate (EVA) or polyvinyl chloride (PVC) bags,
• with polyethylene (PE), polyurethane (PUR), ethyl vinyl acetate (EVA), polyolefine thermoplastic (TP) or polyvinyl chloride (PVC) infusion sets,
• with polypropylene (PP) syringes for syringe pump.

Care must be taken to ensure aseptic handling when preparing the infusion.

Erbitux 5 mg/mL must be prepared as follows:

• For administration with infusion pump or gravity drip (diluted with sterile sodium chloride 9 mg/mL (0.9%) solution): Take an infusion bag of adequate size of sterile sodium chloride 9 mg/mL (0.9%) solution. Calculate the required volume of Erbitux. Remove an adequate volume of the sodium chloride solution from the infusion bag, using an appropriate sterile syringe with a suitable needle. Take an appropriate sterile syringe and attach a suitable needle. Draw up the required volume of Erbitux from a vial. Transfer the Erbitux into the prepared infusion bag. Repeat this procedure until the calculated volume has been reached. Connect the infusion line and prime it with the diluted Erbitux before starting the infusion. Use a gravity drip or an infusion pump for administration. Set and control the rate as explained in section 4.2.
• For administration with infusion pump or gravity drip (undiluted): Calculate the required volume of Erbitux. Take an appropriate sterile syringe (minimum 50 mL) and attach a suitable needle. Draw up the required volume of Erbitux from a vial. Transfer the Erbitux into a sterile evacuated container or bag. Repeat this procedure until the calculated volume has been reached. Connect the infusion line and prime it with Erbitux before starting the infusion. Set and control the rate as explained in section 4.2.
• For administration with a syringe pump: Calculate the required volume of Erbitux. Take an appropriate sterile syringe and attach a suitable needle. Draw up the required volume of Erbitux from a vial. Remove the needle and put the syringe into the syringe pump. Connect the infusion line to the syringe, set and control the rate as explained in section 4.2 and start the infusion after priming the line with Erbitux or sterile sodium chloride 9 mg/mL (0.9%) solution. If necessary, repeat this procedure until the calculated volume has been infused.