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STRENSIQ

ASFOTASE ALFA

Standard Dose

2 DOSAGE AND ADMINISTRATION Perinatal/Infantile-Onset HPP ( 2.2 ) Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen. The dose may be increased to 3 mg/kg three times per week for insufficient efficacy. Juvenile-Onset HPP ( 2.3 ) Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen. Preparation and Weight-Based Dosing ( 2.4 ): Caution: Do not use the 80 mg/0.8 mL vial in pediatric patients weighing less than 40 kg because the systemic asfotase alfa exposure 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 full prescribing information for tables of weight-based dosing by treatment regimen. Administration ( 2.5 ): For subcutaneous injection only. Rotate injection sites. Do not administer to areas that are reddened, inflamed or swollen. 2.1 Recommendations Prior to STRENSIQ Treatment Initiate STRENSIQ under the supervision of a healthcare provider with appropriate medical monitoring and support measures [see Warnings and Precautions (5.1) ]. 2.2 Dosage for Perinatal/Infantile-Onset HPP The recommended dosage regimen of STRENSIQ for the treatment of perinatal/infantile-onset HPP is 6 mg/kg per week administered subcutaneously as either: 2 mg/kg three times per week, or 1 mg/kg six times per week. Injection site reactions may limit the tolerability of the six times per week regimen [see Adverse Reactions (6.1) ]. The dose of STRENSIQ may be increased for lack of efficacy (e.g., no improvement in respiratory status, growth, or radiographic findings) up to 9 mg/kg per week administered subcutaneously as 3 mg/kg three times per week. 2.3 Dosage for Juvenile-Onset HPP The recommended dosage regimen of STRENSIQ for the treatment of juvenile-onset HPP is 6 mg/kg per week administered subcutaneously as either: 2 mg/kg three times per week, or 1 mg/kg six times per week. Injection site reactions may limit the tolerability of the six times per week regimen [see Adverse Reactions (6.1) ]. 2.4 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 (3) , Clinical Pharmacology (12.3) ] . 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 (2.2) ] (Table 3). Table 1: Weight-Based Dosing for Administration of 2 mg/kg Three Times per Week Body Weight (kg) Do not use the 80 mg/0.8 mL vial of STRENSIQ in pediatric patients weighing less than 40 kg [see Clinical Pharmacology (12.3) ] . Dose to Inject Volume to Inject Vial Configuration 3 6 mg 0.15 mL 18 mg/0.45 mL 4 8 mg 0.2 mL 18 mg/0.45 mL 5 10 mg 0.25 mL 18 mg/0.45 mL 6 12 mg 0.3 mL 18 mg/0.45 mL 7 14 mg 0.35 mL 18 mg/0.45 mL 8 16 mg 0.4 mL 18 mg/0.45 mL 9 18 mg 0.45 mL 18 mg/0.45 mL 10 20 mg 0.5 mL 28 mg/0.7 mL 15 30 mg 0.75 mL 40 mg/1 mL 20 40 mg 1 mL 40 mg/1 mL 25 50 mg 1.25 mL Two 28 mg/0.7 mL vials 30 60 mg 1.5 mL Two 40 mg/1 mL vials 35 70 mg 1.75 mL Two 40 mg/1 mL vials 40 80 mg 0.8 mL 80 mg/0.8 mL 50 100 mg 1 mL Two 80 mg/0.8 mL vials 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 Table 2: Weight-Based Dosing for Administration of 1 mg/kg Six Times per Week Body Weight (kg) Do not use the 80 mg/0.8 mL vial of STRENSIQ in pediatric patients weighing less than 40 kg [see Clinical Pharmacology (12.3) ] . Dose to Inject Volume to Inject Vial Configuration 3 3 mg 0.08 mL 18 mg/0.45 mL 4 4 mg 0.1 mL 18 mg/0.45 mL 5 5 mg 0.13 mL 18 mg/0.45 mL 6 6 mg 0.15 mL 18 mg/0.45 mL 7 7 mg 0.18 mL 18 mg/0.45 mL 8 8 mg 0.2 mL 18 mg/0.45 mL 9 9 mg 0.23 mL 18 mg/0.45 mL 10 10 mg 0.25 mL 18 mg/0.45 mL 15 15 mg 0.38 mL 18 mg/0.45 mL 20 20 mg 0.5 mL 28 mg/0.7 mL 25 25 mg 0.63 mL 28 mg/0.7 mL 30 30 mg 0.75 mL 40 mg/1 mL 35 35 mg 0.88 mL 40 mg/1 mL 40 40 mg 1 mL 40 mg/1 mL 50 50 mg 0.5 mL 80 mg/0.8 mL 60 60 mg 0.6 mL 80 mg/0.8 mL 70 70 mg 0.7 mL 80 mg/0.8 mL 80 80 mg 0.8 mL 80 mg/0.8 mL 90 90 mg 0.9 mL Two 80 mg/0.8 mL vials 100 100 mg 1 mL Two 80 mg/0.8 mL vials Table 3: Weight-Based Dosing for Administration of 3 mg/kg Three Times per Week – Only for Perinatal/Infantile-Onset HPP A regimen of 3 mg/kg three times per week is recommended only for patients with perinatal/infantile-onset HPP [see Dosage and Administration (2.2) ] Body Weight (kg) Do not use the 80 mg/0.8 mL vial of STRENSIQ in pediatric patients weighing less than 40 kg [see Clinical Pharmacology (12.3) ] . Dose to Inject Volume to Inject Vial Configuration 3 9 mg 0.23 mL 18 mg/0.45 mL 4 12 mg 0.3 mL 18 mg/0.45 mL 5 15 mg 0.38 mL 18 mg/0.45 mL 6 18 mg 0.45 mL 18 mg/0.45 mL 7 21 mg 0.53 mL 28 mg/0.7 mL 8 24 mg 0.6 mL 28 mg/0.7 mL 9 27 mg 0.68 mL 28 mg/0.7 mL 10 30 mg 0.75 mL 40 mg/1 mL 15 45 mg 1.13 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 28 mg/0.7 mL vials 20 60 mg 1.5 mL Two 40 mg/1 mL vials 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. 2.5 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 (5.2) , Adverse Reactions (6.1) ] . 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.

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE STRENSIQ ® is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).

Summary

Indications and usage 1 INDICATIONS AND USAGE STRENSIQ ® is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).

STRENSIQ is a tissue nonspecific alkaline phosphatase indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP). ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Perinatal/Infantile-Onset HPP ( 2.2 ) Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week.

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE STRENSIQ ® is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP). STRENSIQ is a tissue nonspecific alkaline phosphatase indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP). ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Perinatal/Infantile-Onset HPP ( 2.2 ) Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen. The dose may be increased to 3 mg/kg three times per week for insufficient efficacy. Juvenile-Onset HPP ( 2.3 ) Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen. Preparation and Weight-Based Dosing ( 2.4 ): Caution: Do not use the 80 mg/0.8 mL vial in pediatric patients weighing less than 40 kg because the systemic asfotase alfa exposure 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 full prescribing information for tables of weight-based dosing by treatment regimen. Administration ( 2.5 ): For subcutaneous injection only. Rotate injection sites. Do not administer to areas that are reddened, inflamed or swollen. 2.1 Recommendations Prior to STRENSIQ Treatment Initiate STRENSIQ under the supervision of a healthcare provider with appropriate medical monitoring and support measures [see Warnings and Precautions (5.1) ]. 2.2 Dosage for Perinatal/Infantile-Onset HPP The recommended dosage regimen of STRENSIQ for the treatment of perinatal/infantile-onset HPP is 6 mg/kg per week administered subcutaneously as either: 2 mg/kg three times per week, or 1 mg/kg six times per week. Injection site reactions may limit the tolerability of the six times per week regimen [see Adverse Reactions (6.1) ]. The dose of STRENSIQ may be increased for lack of efficacy (e.g., no improvement in respiratory status, growth, or radiographic findings) up to 9 mg/kg per week administered subcutaneously as 3 mg/kg three times per week. 2.3 Dosage for Juvenile-Onset HPP The recommended dosage regimen of STRENSIQ for the treatment of juvenile-onset HPP is 6 mg/kg per week administered subcutaneously as either: 2 mg/kg three times per week, or 1 mg/kg six times per week. Injection site reactions may limit the tolerability of the six times per week regimen [see Adverse Reactions (6.1) ]. 2.4 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 (3) , Clinical Pharmacology (12.3) ] . 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 (2.2) ] (Table 3). Table 1: Weight-Based Dosing for Administration of 2 mg/kg Three Times per Week Body Weight (kg) Do not use the 80 mg/0.8 mL vial of STRENSIQ in pediatric patients weighing less than 40 kg [see Clinical Pharmacology (12.3) ] . Dose to Inject Volume to Inject Vial Configuration 3 6 mg 0.15 mL 18 mg/0.45 mL 4 8 mg 0.2 mL 18 mg/0.45 mL 5 10 mg 0.25 mL 18 mg/0.45 mL 6 12 mg 0.3 mL 18 mg/0.45 mL 7 14 mg 0.35 mL 18 mg/0.45 mL 8 16 mg 0.4 mL 18 mg/0.45 mL 9 18 mg 0.45 mL 18 mg/0.45 mL 10 20 mg 0.5 mL 28 mg/0.7 mL 15 30 mg 0.75 mL 40 mg/1 mL 20 40 mg 1 mL 40 mg/1 mL 25 50 mg 1.25 mL Two 28

Boxed Warning

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate STRENSIQ under the supervision of a healthcare provider with appropriate medical monitoring and support measures. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue STRENSIQ and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1) ] . WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS See full prescribing information for complete boxed warning. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. ( 5.1 ) Initiate STRENSIQ under the supervision of a healthcare provider with appropriate medical monitoring and support measures. ( 5.1 ) If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue STRENSIQ and immediately initiate appropriate medical treatment, including use of epinephrine. ( 5.1 )

Monitoring

• 5 WARNINGS AND PRECAUTIONS Lipodystrophy: Localized reactions were reported after several months of treatment; follow proper injection technique and rotate injection sites.
• ( 5.2 ) Ectopic Calcifications (eye and kidneys): Monitor using ophthalmologic examinations and renal ultrasounds at baseline and periodically during treatment.
• ( 5.3 ) Possible Immune-Mediated Clinical Effects: Evaluate patients for antibody formation if clinically indicated.
• ( 5.4 ) 5.1 Hypersensitivity Reactions Including Anaphylaxis Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with enzyme replacement therapies, including STRENSIQ.

Interaction Notes

• 7 DRUG INTERACTIONS Drug Interference with Laboratory Tests: Alkaline Phosphatase (ALP) is used as a detection reagent in many laboratory tests and the presence of asfotase alfa in clinical laboratory samples could result in erroneous test results.
• Inform laboratory personnel and discuss use of an alternative testing platform for patients on treatment.
• ( 7.1 ) Serum Alkaline Phosphatase : Serum ALP measurements are expected to be elevated during treatment and may be unreliable for clinical decision making.
• ( 7.1 ) 7.1 Drug Interference with Laboratory Tests Laboratory Tests Utilizing Alkaline Phosphatase as a Detection Reagent Studies have shown that there is analytical interference between asfotase alfa and laboratory tests that utilize an alkaline phosphatase (ALP)-conjugated test system, rendering erroneous test results in patients treated with STRENSIQ.