TEPEZZA Powder for concentrate for solution for infusion Ref.[115480] Active ingredients: Teprotumumab

Treatment with this medicinal product must be initiated and supervised by a physician experienced in the diagnosis and treatment of thyroid eye disease. It should be administered by a healthcare professional and under the supervision of a physician with access to appropriate medical support to manage infusion-related reactions.

Posology

Dosing is based on the patient's actual body weight. The recommended dose is 10 mg/kg of body weight for the initial dose followed by 20 mg/kg of body weight for 7 additional doses given once every three weeks as an intravenous infusion.

For the first 2 infusions, the diluted solution is administered as an intravenous infusion over at least 90 minutes. If well tolerated, infusions 3 to 8 can be administered over 60 minutes every three weeks (see Method of administration). Clinical response is expected with 8 doses of treatment. Additional doses should not be administered if response is not achieved with this regimen.

Recommended pre-medication

For patients experiencing immediate hypersensitivity reactions or infusion-related reactions during the first two infusions of teprotumumab, pre-medication with an antihistamine, antipyretic, corticosteroid products and/or administering all subsequent infusions at a slower infusion rate is recommended (see section 4.4).

Special populations

Elderly

No dose adjustment is considered necessary in patients over 65 years old (see section 5.2).

Renal impairment

Renal impairment is generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies. Therefore, no dose adjustment is considered necessary for patients with renal impairment (see section 5.2).

Hepatic impairment

Hepatic impairment is generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies. Therefore, no dose adjustment is considered necessary for patients with hepatic impairment (see section 5.2).

Paediatric population

Teprotumumab should not be used in children from birth to adolescence before growth is complete because of safety concerns related to potential decrease in bone mass and decrease in body weight gains (see section 5.3).

The safety and efficacy of teprotumumab in adolescents whose growth is complete to less than 18 years has not been established. No data are available.

Method of administration

• This medicinal product must be administered as an intravenous infusion. It must not be administered as an intravenous push or bolus.
• Prior to infusion:
  • the powder must be reconstituted with water for injection.
  • The reconstituted solution must be further diluted in sodium chloride 9 mg/mL (0.9%) solution for infusion.
• TEPEZZA must not be co-administered with other medicinal products through the same infusion line.
• For the first 2 infusions, the diluted solution must be administered intravenously over at least 90 minutes. If well tolerated, the minimum time for subsequent infusions can be reduced to 60 minutes.
• If the 60-minute infusion is not well tolerated, the minimum time for subsequent infusions should remain at 90 minutes, the rate of infusion should be reduced and pre-medication is recommended for subsequent infusions.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

There is no known antidote for teprotumumab overdose. Treatment consists of discontinuation of the medicinal product and supportive therapy.

Lyophilised powder in unopened vial:

3 years.

Reconstituted and diluted infusion solution:

Chemical and physical in-use stability of the reconstituted solution in the vial has been demonstrated for up to 4 hours at room temperature (20°C–25°C) or up to 48 hours at 2°C to 8°C storage condition.

Chemical and physical in-use stability of the diluted solution in the infusion bag has been demonstrated for 24 hours at 2°C to 8ºC followed by 24 hours at room temperature (20°C–25°C) storage condition.

From a microbiological point of view, the product should be used immediately. 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°C to 8°C, unless reconstitution and dilution has taken place in controlled and validated aseptic conditions. If refrigerated prior to administration, the diluted solution should be at room temperature prior to infusion.

Store in a refrigerator (2°C–8°C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

20 mL type I clear glass vial, with a grey stopper (flurotec coated chlorobutyl) and an aluminium seal with a polypropylene matte red flip-off cap.

Each carton contains one vial.

TEPEZZA should be prepared by a healthcare professional using aseptic technique to ensure the sterility of the prepared solution.

After reconstitution, teprotumumab is a nearly colourless or slightly brown, clear to opalescent solution which is free of foreign particulate matter. The reconstituted solution should be inspected for particular matter and discolouration prior to administration. The vial should be discarded if particulate matter is present or discolouration is observed. Refer to section 6.3 for stability after reconstitution.

Preparation of the medicinal product before administration

Step 1: Calculate the dose (mg) and determine the number of vials needed for the 10 or 20 mg/kg dose based on patient weight. Each vial contains 500 mg of teprotumumab.

Step 2: Using appropriate aseptic technique, reconstitute each vial with 10 mL of water for injections. Ensure that the stream of diluent is not directed onto the lyophilised powder, which has a cake-like appearance. Do not shake, but gently swirl the solution by rotating the vial until the lyophilised powder is dissolved. The reconstituted solution has a total volume of 10.5 mL. Withdraw 10.5 mL of reconstituted solution to obtain 500 mg. After reconstitution, the final concentration is 47.6 mg/mL.

Step 3: The reconstituted solution must be further diluted in sodium chloride 9 mg/mL (0.9%) solution for infusion, prior to infusion. To prepare the diluted solution, use 100 mL infusion bags for a dose less than 1 800 mg, and 250 mL infusion bags for a dose equal of greater than 1 800 mg. To maintain a constant volume in the infusion bag, a sterile syringe and needle should be used to remove the calculated volume equivalent to the amount of the reconstituted solution to be placed into the infusion bag. The volume of sodium chloride 9 mg/mL (0.9%) solution withdrawn must be discarded.

Step 4: Withdraw the required volume from the reconstituted vial(s) based on the patient's weight (in kg) and transfer into an intravenous bag containing sodium chloride 9 mg/mL (0.9%) solution for infusion. Mix the diluted solution by gentle inversion. Do not shake. If refrigerated prior to administration, allow the diluted solution to reach room temperature prior to infusion. Care should be taken to ensure the sterility of the prepared solution.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

No incompatibilities between teprotumumab and polyethylene (PE), polyvinyl chloride (PVC), polyurethane (PUR) or polyolefin (PO) bags and intravenous administration sets have been observed.