MEPSEVII Concentrate for solution for infusion Ref.[7644] Active ingredients: Vestronidase alfa

Treatment should be supervised by a healthcare professional experienced in the management of patients with MPS VII or other inherited metabolic disorders. Administration of vestronidase alfa should be carried out by an appropriately trained healthcare professional with the ability to manage medical emergencies.

Posology

The recommended dose of vestronidase alfa is 4 mg/kg of body weight administered by intravenous infusion every two weeks.

To minimise the risk of hypersensitivity reactions, a non-sedating antihistamine with or without an antipyretic medicinal product should be administered 30-60 minutes prior to the start of the infusion (see section 4.4). Infusion should be avoided if the patient has an acute febrile or respiratory illness at the time.

Special populations

Elderly

The safety and efficacy of vestronidase alfa in patients older than 65 years have not been established. No alternative dose regimen is recommended in these patients (see section 5.1).

Renal and hepatic impairment

The safety and efficacy of vestronidase alfa in patients with renal or hepatic impairment have not been evaluated. No alternative dose regimen is recommended in these patients.

Paediatric population

The posology in the paediatric population is the same as in adults. Currently available data are described in section 4.8 and section 5.1.

Method of administration

For intravenous use only.

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

The total diluted volume of the solution for infusion should be administered with a rate titration regimen over approximately 4 hours.

The rate of infusion should be as follows: in the first hour, 2.5% of the total volume will be infused, with the balance infused over the subsequent three hours. Any dead space in the lines should be accounted for to ensure 2.5% of the total infusion volume is delivered into the patient’s bloodstream during the first hour of infusion. The lowest rate administered to a patient in the clinical development program was 0.5 mL/hour during the first 30 minutes of infusion, followed by 1 mL/hour over the next 30 minutes, equalling 0.75 mL as the lowest total volume infused during the first hour.

Do not flush the line containing vestronidase alfa to avoid a rapid bolus of infused enzyme. Due to the low infusion rate, additional sodium chloride 9 mg/mL (0.9%) solution for infusion may be added through a separate line (piggyback or Y tube) to maintain sufficient intravenous flow. After the first hour, the rate can be increased to infuse the remainder of the solution for infusion over 3 hours as tolerated according to the recommended rate guidelines in Table 2.

The infusion rate may be slowed, temporarily interrupted or discontinued in the event of hypersensitivity reactions (see section 4.4).

Do not infuse Mepsevii with other medicinal products in the infusion tubing. Compatibility with other medicinal products has not been evaluated.

There is no experience with overdoses of vestronidase alfa. For the management of adverse reactions, see sections 4.4 and 4.8.

Shelf life: 36 months.

After dilution: Chemical and physical in-use stability of the diluted medicinal product has been demonstrated for up to 36 hours under refrigeration at 2°C–8°C followed by up to 6 hours at room temperature up to a maximum of 25°C.

From a microbiological safety point of view, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user, but should normally not be longer than 36 hours at 2°C–8°C followed by up to 6 hours at room temperature up to a maximum of 25°C.

Store in a refrigerator (2°C–8°C).

Do not freeze.

Store in the original package in order to protect from light.

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

Colourless glass vial (Ph. Eur. Type I) with a rubber stopper with fluoro-resin coating, and an aluminium over seal with a plastic flip-off cap.

Pack size: 1 vial containing 5 mL of concentrate for solution for infusion.

Each vial of Mepsevii is intended for single use only. Mepsevii must be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection using aseptic technique according to the steps described below. The diluted solution for infusion should be administered to patients using a low-protein binding infusion bag and set (a non di (2-ethylhexyl) phthalate [DEHP] bag could be used) and the application of an infusion set equipped with an in-line, low-protein binding 0.2 μm filter is recommended.

1. Determine the number of vials to be diluted based on the patient’s actual weight and the recommended dose of 4 mg/kg, using the following calculations (a-b):
a. Total dose (mg) = Patient’s weight (kg) x 4 mg/kg (recommended dose)
b. Total number of vials = Total dose (mg) divided by 10 mg/vial
2. Round to the next whole vial and remove the required number of vials (refer to Table 2) from the refrigerator to allow them to reach room temperature up to a maximum of 25°C. Do not heat, microwave or shake vials.
a. Volume (mL) of calculated dose = Total dose (mg) divided by the 2 mg/mL concentration
3. Dilute the calculated dose 1:1 using equal volume of sodium chloride 9 mg/mL (0.9%) solution for injection for intravenous infusion. The total infusion volume is based on the total Mepsevii dose and volume (refer to Table 2). The above calculated dose diluted 1:1 in sodium chloride 9 mg/mL (0.9%) solution for injection should be added to a new empty infusion bag. Dilution preparation should be done at room temperature.
4. Prior to withdrawing Mepsevii from the vial, visually inspect for particulate matter and discolouration. The Mepsevii concentrate solution for infusion should be colourless to slightly yellow. Do not use if the solution is discoloured or if there is particulate matter in the solution.
5. Slowly withdraw Mepsevii from the appropriate number of vials using caution to avoid excessive agitation and any air or frothing. A sufficiently large needle (18 gauge) should be used to minimise bubbles in the solution.
6. Slowly add Mepsevii to the infusion bag using care to avoid agitation, ensuring liquid to liquid contact without generating bubbles or turbulence.
7. Gently rock the infusion bag to ensure proper distribution of Mepsevii. Do not shake the solution.

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

Table 2. Recommended infusion rate schedule by patient weight for administration of Mepsevii at recommended dose of 4 mg/kg: