Asfotase alfa

4 CONTRAINDICATIONS None. None. 5 WARNINGS AND PRECAUTIONS Lipodystrophy: Localized reactions were reported after several months of treatment; follow proper injection technique and rotate injection sites. Ectopic Calcifications (eye and kidneys): Monitor using ophthalmologic examinations and renal ultrasounds at baseline and periodically during treatment.

Advise patients to follow proper injection technique and to rotate injection sites [see Dosage and Administration ] . 5.3 Ectopic Calcifications Patients with HPP are at increased risk for developing ectopic calcifications. Events of ectopic calcification, including ophthalmic (conjunctival and corneal) and renal (nephrocalcinosis, nephrolithiasis), have been reported in the clinical trial experience with STRENSIQ.

There was insufficient information to determine whether or not the reported events were consistent with the disease or due to STRENSIQ. No visual changes or changes in renal function were reported resulting from the occurrence of ectopic calcifications. Ophthalmology examinations and renal ultrasounds are recommended at baseline and periodically during treatment with STRENSIQ to monitor for signs and symptoms of ophthalmic and renal ectopic calcifications and for changes in vision or renal function. 5.4 Possible Immune-Mediated Clinical Effects In clinical trials, most STRENSIQ-treated patients developed anti-asfotase alfa antibodies and neutralizing antibodies which resulted in reduced systemic exposure of asfotase alfa [see Immunogenicity ].

Preparation and Weight-Based Dosing Tables Caution: Do not use the 80 mg/0.8 mL vial of STRENSIQ in pediatric patients weighing less than 40 kg because the systemic exposure of asfotase alfa achieved with the 80 mg/0.8 mL vial (higher concentration) is lower than that achieved with the other strength vials (lower concentration).

A lower exposure may not be adequate for this subgroup of patients [see Dosage Forms and Strengths , Clinical Pharmacology ] . 1. Determine the total weekly volume needed for the prescribed dosage based on the patient's weight and recommended dosage. Follow these steps to determine the patient dose. Total weekly dose (mg) = patient's weight (kg) × prescribed dose (mg/kg/week) Total injection volume (mL) per week = Total dose (mg/week) divided by the STRENSIQ concentration (40 mg/mL or 100 mg/mL).

Note product concentrations are: 40 mg/mL (vial strengths 18 mg/0.45 mL, 28 mg/0.7 mL, 40 mg/mL) or 100 mg/mL (vial strength 80 mg/0.8 mL). Round total injection volume to the nearest hundredth of a mL Total number of vials per week = Total injection volume divided by vial volume (mL) 2. Determine the number of injection days per week (three or six per week). 3.

Determine dose per injection day. Patient weights should be rounded to the nearest kilogram when determining dose. Use the following tables for guidance, for patients administering 2 mg/kg three times per week (Table 1), 1 mg/kg six times per week (Table 2) and for dose escalations to 3 mg/kg three times per week, recommended only for patients with perinatal/infantile-onset HPP [see Dosage and Administration ] (Table 3). [See table below.] 60 120 mg 1.2 mL When preparing a volume for injection greater than 1 mL, split the volume equally between two syringes, and administer two injections.

When administering the two injections, use two separate injection sites. Two 80 mg/0.8 mL vials 70 140 mg 1.4 mL Two 80 mg/0.8 mL vials 80 160 mg 1.6 mL Two 80 mg/0.8 mL vials [See table below.] 100 100 mg 1 mL Two 80 mg/0.8 mL vials [See table below.] 25 75 mg 1.88 mL Two 40 mg/1 mL vials 4. Take the unopened STRENSIQ vial(s) out of the refrigerator 15 to 30 minutes before injecting to allow the liquid to reach room temperature.

Do not warm STRENSIQ in any other way (for example, do not warm it in a microwave or in hot water). 5. Inspect the solution in the vial(s) for particulate matter and discoloration. STRENSIQ is supplied as a clear, slightly opalescent or opalescent, colorless to slightly yellow aqueous solution; a few small translucent or white particles may be present.

Discard any vial(s) not consistent with this appearance. 6. Assemble injection supplies. Administer STRENSIQ using sterile disposable 1 mL syringes and ½ inch injection needles, between 25 to 29 gauge are recommended. The use of two different gauge needles is recommended, a larger bore needle (e.g. 25 gauge) for withdrawal of the medication, and a smaller bore needle (e.g. 29 gauge) for the injection.

For doses greater than 1 mL, the injection volume should be split equally between two 1 mL syringes. Always use a new syringe and needle for each injection. 7. Remove vial cap, aseptically prepare the vial and insert the syringe into the vial to withdraw the prescribed dose for administration. Do not shake. 8. Remove any air bubbles in the syringe and verify the correct dose. 9.

STRENSIQ vials are for one time use only. Discard any unused product.

Administration STRENSIQ is for subcutaneous injection only. When administering two injections, use two separate injection sites. Administer STRENSIQ within 3 hours upon removal of the vial(s) from refrigeration. Rotate the injection from among the following sites to reduce the risk of lipodystrophy: abdominal area, thigh, deltoid, or buttocks [see Warnings and Precautions , Adverse Reactions ] .

Do NOT administer injections in areas that are reddened, inflamed, or swollen. Inject STRENSIQ subcutaneously into the determined site and properly dispose of the syringe and the needle.