2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

MEPSEVII should be administered under the supervision of a healthcare professional with the capability to manage anaphylaxis. Premedication is recommended 30 to 60 minutes prior to the start of the infusion [see Dosage and Administration (2.2)].

The recommended dosage of MEPSEVII is 4 mg/kg administered by intravenous infusion every two weeks.

Administer the infusion over approximately 4 hours. Infuse the first 2.5% of the total volume over the first hour. After the first hour, increase the infusion rate as tolerated in order to complete infusion over the following 3 hours according to the recommended rate guidelines in Table 1 [see Dosage and Administration (2.4)].

2.2 Premedication

Administration of a non-sedating antihistamine with or without an anti-pyretic medication is recommended 30 to 60 minutes prior to the start of the infusion for patient comfort.
Follow the instructions in Table 1 for the rate of MEPSEVII infusion [see Dosage and Administration (2.4)].
Observe patients closely during the infusion and following the infusion for a minimum of 60 minutes for the development of anaphylaxis [see Warnings and Precautions (5.1)].
Discontinue the infusion immediately if the patient experiences a severe systemic reaction, including anaphylaxis [see Warnings and Precautions (5.1)].

2.3 Preparation Instructions

Prepare MEPSEVII according to the following steps using aseptic technique:

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 from the refrigerator to allow them to reach room temperature. Do not heat, microwave or shake vials.

a. Volume (mL) of calculated dose = Total dose (mg) divided by the 2 mg/mL concentration

3. The final solution will be a 1:1 dilution of MEPSEVII with 0.9% Sodium Chloride Injection, USP. More than 1:1 dilution may be used if the patient can tolerate additional infusion volume, taking into consideration cardiac function and fluid status.

4. For a 1:1 dilution, prepare the solution at room temperature, as follows:

a. Select an empty infusion bag, sized upon the total volume of the final solution.

b. Prior to withdrawing MEPSEVII from the vial, visually inspect the solution for particulate matter and discoloration. Because this is a protein solution, slight flocculation (thin translucent fibers) may occur. The MEPSEVII solution should be colorless to slightly yellow. Discard if the solution is discolored or if there is particulate matter in the solution.

c. Slowly withdraw the volume of the calculated MEPSEVII dose from the appropriate number of vials (step 2a) using caution to avoid excessive agitation and any air or frothing. Use a sufficiently large needle (18 gauge) to minimize bubbles in the solution.

d. Slowly add MEPSEVII to the infusion bag using care to avoid agitation, ensuring liquid to liquid contact without generating bubbles or turbulence.

e. Add 0.9% Sodium Chloride Injection, USP equal to the volume of MEPSEVII to the infusion bag.

f. Gently rock the infusion bag to ensure proper distribution of MEPSEVII. Do not shake the solution.

2.4 Administration Instructions

Administer MEPSEVII as follows:

The rate of infusion: In the first hour infuse 2.5% of the total volume, and infuse the remaining volume over the subsequent three hours (see Table 1). Account for any dead space in the lines to ensure 2.5% of the total infusion volume is delivered into the patient's bloodstream during the first hour of infusion.
Use an infusion set equipped with an in-line, low-protein binding 0.2 micron filter to administer the diluted MEPSEVII solution.
Do not flush the line containing MEPSEVII to avoid a rapid bolus of infused enzyme. Due to the low infusion rate, additional saline may be added through a separate line (piggyback or Y tube) to maintain sufficient intravenous flow to prevent clotting or line blockage.
Do not infuse with other products in the infusion tubing. Compatibility with other products has not been evaluated.
Use MEPSEVII immediately after dilution and complete the infusion within 42 hours from the time of dilution. Discard any unused product.

Stability

If immediate use is not possible, the diluted solution may be stored up to 36 hours under refrigeration at 2°C to 8°C (36°F to 46°F) followed by up to 6 hours at room temperature up to a maximum of 25°C (77°F).

Table 1. Recommended Infusion Rate Schedule by Patient Weight for Administration of MEPSEVII at Recommended Dose of 4 mg/kg
Patient Weight Range (kg)	Total MEPSEVII Dose Range (mg)	Total MEPSEVII Volume (rounded) (mL)	Total Infusion Volume of Drug and diluent (infused over 4 hours) (mL)	Infusion Rate for 1st Hour (2.5%) (mL/h)	Infusion Rate per Hour for Subsequent 3 Hours (97.5%/3) (mL/h)
3.5-5.9	14-23.6	10	20	0.5	6.5
6-8.4	24-33.6	15	30	0.8	9.8
8.5-10.9	34-43.6	20	40	1	13
11-13.4	44-53.6	25	50	1.3	16.3
13.5-15.9	54-63.6	30	60	1.5	19.5
16-18.4	64-73.6	35	70	1.8	22.8
18.5-20.9	74-83.6	40	80	2	26
21-23.4	84-93.6	45	90	2.3	29.3
23.5-25.9	94-103.6	50	100	2.5	32.5
26-28.4	104-113.6	55	110	2.8	35.8
28.5-30.9	114-123.6	60	120	3	39
31-33.4	124-133.6	65	130	3.3	42.3
33.5-35.9	134-143.6	70	140	3.5	45.5
36-38.4	144-153.6	75	150	3.8	48.8
38.5-40.9	154-163.6	80	160	4	52
41-43.4	164-173.6	85	170	4.3	55.3
43.5-45.9	174-183.6	90	180	4.5	58.5
46-48.4	184-193.6	95	190	4.8	61.8
48.5-50.9	194-203.6	100	200	5	65
51-53.4	204-213.6	105	210	5.3	68.3
53.5-55.9	214-223.6	110	220	5.5	71.5
56-58.4	224-233.6	115	230	5.8	74.8
58.5-60.9	234-243.6	120	240	6	78
61-63.4	244-253.6	125	250	6.3	81.3
63.5-65.9	254-263.6	130	260	6.5	84.5
66-68.4	264-273.6	135	270	6.8	87.8
68.5-70.9	274-283.6	140	280	7	91