Asfotase alfa

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# Overview
Asfotase alfa is a tissue nonspecific alkaline phosphatase that is FDA approved for the treatment of patients with perinatal/infantile and juvenile-onset hypophosphatasia (HPP)..   Common adverse reactions include injection site reactions, lipodystrophy, ectopic calcifications and hypersensitivity reactions..

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
There is limited information regarding Asfotase alfa FDA-Labeled Indications and Dosage (Adult) in the drug label.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Asfotase alfa in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Asfotase alfa in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)

### Perinatal/Infantile-Onset HPP
- 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
- 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
- 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.

### Administration
- For subcutaneous injection only.
- Rotate injection sites.
- Do not administer to areas that are reddened, inflamed or swollen.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Asfotase alfa in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Asfotase alfa in pediatric patients.

# Contraindications
None.

# Warnings

### Hypersensitivity Reactions
- Hypersensitivity reactions, including anaphylaxis, have been reported in Asfotase alfa-treated patients.
- Signs and symptoms consistent with anaphylaxis included difficulty breathing, choking sensation, nausea, periorbital edema, and dizziness.
- These reactions have occurred within minutes after subcutaneous administration of Asfotase alfa and can occur in patients on treatment for more than one year.
- Other hypersensitivity reactions have also been reported in Asfotase alfa-treated patients, including vomiting, fever, headache, flushing, irritability, chills, skin erythema, rash, pruritus and oral hypesthesia.
- If a severe hypersensitivity reaction occurs, discontinue Asfotase alfa treatment and initiate appropriate medical treatment.
- Consider the risks and benefits of re-administering Asfotase alfa to individual patients following a severe reaction.
- If the decision is made to re-administer the product, monitor patients for a reoccurrence of signs and symptoms of a severe hypersensitivity reaction.

### Lipodystrophy
- Localized lipodystrophy, including lipoatrophy and lipohypertrophy, has been reported at injection sites after several months in patients treated with Asfotase alfa in clinical trials.
- Advise patients to follow proper injection technique and to rotate injection sites.

### Ectopic Calcifications
- Patients with HPP are at increased risk for developing ectopic calcifications.
- In clinical trials with Asfotase alfa, 14 cases (14%) of ectopic calcification of the eye including the cornea and conjunctiva, and the kidneys (nephrocalcinosis) were reported.
- There was insufficient information to determine whether or not the reported events were consistent with the disease or due to Asfotase alfa.
- 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 Asfotase alfa to monitor for signs and symptoms of ophthalmic and renal ectopic calcifications and for changes in vision or renal function.

# Adverse Reactions

## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- The data described below reflect exposure to Asfotase alfa in 99 patients with perinatal/infantile- or juvenile-onset HPP (age 1 day to 58 years) treated with Asfotase alfa, most for more than 2 years (range 1 day to 312 weeks ): 51 patients received at least 96 weeks (24 months) of treatment and 39 patients received 168 weeks (42 months) or more of treatment.

### Common Adverse Reactions
- Overall, the most common adverse reactions reported were injection site reactions (63%).
- Other common adverse reactions included lipodystrophy (28%), ectopic calcifications (14%), and hypersensitivity reactions (12%).
- Table 4 summarizes the adverse reactions that occurred at a rate of at least 10% in clinical trials following subcutaneous injection of Asfotase alfa, by patient population and Asfotase alfa dosage regimen.
- The frequency of injection site reactions, lipodystrophy and ectopic calcification were higher in patients with juvenile-onset HPP as compared to perinatal/infantile-onset HPP patients.
- The majority of injection site reactions resolved within a week.
- Two patients experienced injection site reactions that led to reductions of their Asfotase alfa dose.
- One patient switched from six times per week dosing to 3 times per week dosing as a result of injection site reactions.
- One other patient experienced a severe injection site reaction of injection site discoloration and withdrew from the trial.
TABLE 4:

### Less Common Adverse Reactions
- Adverse reactions that occurred at rates less than 1% included:
Hypocalcemia
Renal stones
Chronic hepatitis
Decreased vitamin B6
- Hypocalcemia
- Renal stones
- Chronic hepatitis
- Decreased vitamin B6

### Immunogenicity
- As with all therapeutic proteins, there is potential for immunogenicity.
- During clinical trials, anti-drug antibodies have been detected in patients receiving treatment with Asfotase alfa using an electrochemiluminescent (ECL) immunoassay.
- Antibody positive samples were tested to determine the presence of neutralizing antibodies based on in vitro inhibition of the catalytic activity of Asfotase alfa.
- Among 98 patients with hypophosphatasia (HPP) enrolled in the clinical trials and who had post-baseline antibody data, 76 (78%) tested positive for anti-drug antibodies at some time point after receiving Asfotase alfa treatment.
- Among those 76 patients, 34 (45%) also showed the presence of neutralizing antibodies.
- No correlation was observed between the anti-drug antibody titer and neutralizing antibody (% inhibition) values.
- Formation of anti-drug antibody resulted in a reduced systemic exposure of asfotase alfa.
- The detection of antibody formation is dependent on the sensitivity and specificity of the assay.
- Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
- For these reasons, comparison of the incidence of the antibodies to Asfotase alfa with the incidence of antibodies to other products may be misleading.

## Postmarketing Experience
There is limited information regarding Asfotase alfa Postmarketing Experience in the drug label.

# Drug Interactions
There is limited information regarding Asfotase alfa Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA):

### Risk Summary
- There are no available human data on Asfotase alfa use in pregnant women to inform a drug associated risk.
- In animal reproduction studies, asfotase alfa administered intravenously to pregnant rats and rabbits during the period of organogenesis showed no evidence of fetotoxicity, embryolethality or teratogenicity at doses causing plasma exposures up to 21 and 24 times, respectively, the exposure at the recommended human dose.
- In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

### Data
- Asfotase alfa administered during the period of organogenesis to rats (from gestation Day 6 to Day 19 post-partum) and rabbits (on gestation days 7 to 19) at intravenous doses up to 50 mg/kg/day, approximately 21 and 24 times the human AUC of 65486 ng.h/mL at 2 mg/kg dose administered three times weekly for a 50 kg individual, respectively did not cause any adverse effects on embryofetal development.
- A pre- and post-natal development study in pregnant rats showed no evidence of adverse effects on pre- and post-natal development at intravenous doses (from Day 6 of gestation to Day 19 postpartum) of asfotase alfa up to 50 mg/kg/day approximately 21 times the human AUC of 65486 ng.h/mL at 2 mg/kg dose administered three times weekly for a 50 kg individual.
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Asfotase alfa in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Asfotase alfa during labor and delivery.

### Nursing Mothers
- There are no data on the presence of asfotase alfa in human milk, the effects on the breastfed infant, or the effects on milk production.
- The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Asfotase alfa and any potential adverse effects on the breastfed infant from asfotase alfa or from the underlying maternal condition.

### Pediatric Use
- The safety and effectiveness of Asfotase alfa have been established in pediatric patients.
- Use of Asfotase alfa is based on 4 prospective, open-label clinical trials conducted in 99 adult and pediatric patients with perinatal/infantile-onset or juvenile-onset HPP.
- The majority of patients were pediatric patients 1 day to 16 years of age (89/99 ) .

### Geriatic Use
- No patients with perinatal/infantile- or juvenile-onset HPP aged 65 years were enrolled in clinical trials of Asfotase alfa.
- Therefore, there is no information available to determine whether patients aged 65 years and over respond differently from younger patients.

### Gender
There is no FDA guidance on the use of Asfotase alfa with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Asfotase alfa with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Asfotase alfa in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Asfotase alfa in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Asfotase alfa in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Asfotase alfa in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Asfotase alfa is for subcutaneous injection only.
1. Administer Asfotase alfa within 1 hour upon removal of the vial(s) from refrigeration.
2. Rotate the injection from among the following sites to reduce the risk of lipodystrophy: abdominal area, thigh, or deltoid.
3. Do NOT administer injections in areas that are reddened, inflamed, or swollen.
4. Inject Asfotase alfa subcutaneously into the determined site and properly dispose of the needle.
5. Asfotase alfa vials are single use only. Discard any unused product.

### Monitoring

### Dosage for Perinatal/Infantile-Onset HPP
- The recommended dosage regimen of Asfotase alfa 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.
- 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.
- The dose of Asfotase alfa 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.

### Dosage for Juvenile-Onset HPP
- The recommended dosage regimen of Asfotase alfa 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.
- 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.

### 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.
1. Determine the volume needed for the prescribed dosage based on the patient's weight and recommended dosage. Follow these steps to determine the patient dose.
2. Determine frequency of weekly injections.
3. Determine dose. 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.(Table:3)
4. 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.
- Do not use the 80 mg/0.8 mL vial of Asfotase alfa in pediatric patients weighing less than 40 kg.
 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.
Table 2: Weight-Based Dosing for Administration of 1 mg/kg Six Times per Week
- Do not use the 80 mg/0.8 mL vial of Asfotase alfa in pediatric patients weighing less than 40 kg.
5. Inspect the solution in the vial(s) for particulate matter and discoloration. Asfotase alfa is supplied as a clear, slightly opalescent or opalescent, colorless to slightly yellow aqueous solution; few small translucent or white particles may be present. Discard any vial(s) not consistent with this appearance.
6. Assemble injection supplies. Administer Asfotase alfa using sterile disposable 1 mL syringes and 12 inch injection needles, between 25 to 29 gauge are recommended. 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.
7. Remove vial cap, aseptically prepare the vial and insert the syringe into the vial to withdraw the prescribed dose for administration.
8. Remove any air bubbles in the syringe and verify the correct dose.

# IV Compatibility
There is limited information regarding the compatibility of Asfotase alfa and IV administrations.

# Overdosage
There is limited information regarding Asfotase alfa overdosage.  If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

# Pharmacology
There is limited information regarding Asfotase alfa Pharmacology in the drug label.

## Mechanism of Action
- HPP is caused by a deficiency in TNSALP enzyme activity, which leads to elevations in several TNSALP substrates, including inorganic pyrophosphate (PPi).
- Elevated extracellular levels of PPi block hydroxyapatite crystal growth which inhibits bone mineralization and causes an accumulation of unmineralized bone matrix which manifests as rickets and bone deformation in infants and children and as osteomalacia (softening of bones) once growth plates close, along with muscle weakness.
- Replacement of the TNSALP enzyme upon Asfotase alfa treatment reduces the enzyme substrate levels.

## Structure
- Asfotase alfa is a formulation of asfotase alfa, which is a soluble glycoprotein composed of two identical polypeptide chains.
- Each chain contains 726 amino acids with a theoretical mass of 161 kDa.
- Each chain consists of the catalytic domain of human tissue non-specific alkaline phosphatase (TNSALP), the human immunoglobulin G1 Fc domain and a deca-aspartate peptide used as a bone targeting domain.
- The two polypeptide chains are covalently linked by two disulfide bonds.
- Asfotase alfa is a tissue nonspecific alkaline phosphatase produced by recombinant DNA technology in a Chinese hamster ovary cell line.
- TNSALP is a metallo-enzyme that catalyzes the hydrolysis of phosphomonoesters with release of inorganic phosphate and alcohol.
- Asfotase alfa has a specific activity of 620 to 1250 units/mg.
- One activity unit is defined as the amount of asfotase alfa required to form 1 mol of p-nitrophenol from pNPP per minute at 37C.
- Asfotase alfa is a sterile, preservative-free, nonpyrogenic, clear, slightly opalescent or opalescent, colorless to slightly yellow, with few small translucent or white particles, aqueous solution for subcutaneous administration.
- Asfotase alfa is supplied in glass single-use vials containing asfotase alfa; dibasic sodium phosphate, heptahydrate; monobasic sodium phosphate, monohydrate; and sodium chloride at a pH between 7.2 and 7.6.
- Table 5 describes the content of Asfotase alfa vial presentations.

## Pharmacodynamics
- Perinatal/infantile- and juvenile-onset HPP patients treated with Asfotase alfa had reductions in plasma TNSALP substrates, PPi and pyridoxal 5'-phosphate (PLP) within 6 to 12 weeks of treatment.
- Reductions in plasma PPi and PLP levels did not correlate with clinical outcomes.
- Bone biopsy data from perinatal/infantile-onset and juvenile-onset HPP patients treated with Asfotase alfa demonstrated decreases in osteoid volume and thickness indicating improved bone mineralization.

## Pharmacokinetics
- Based on data in 38 HPP patients, the pharmacokinetics of asfotase alfa exhibit dose proportionality across the dose range of 0.3 mg/kg to 3 mg/kg and appear to be time-independent.
- Steady state exposure was achieved as early as three weeks after the administration of the first dose.
- The elimination half-life following subcutaneous administration was approximately 5 days.
- Table 6 summarizes the pharmacokinetic parameters following multiple doses in 20 HPP patients after subcutaneous administration of Asfotase alfa at 2 mg/kg three times per week in Study 2 (age of less than or equal to 5 years) and Study 3 (age of greater than 5 to 12 years), indicating the pharmacokinetics were similar between patients in the two age groups.
- Population PK analysis of asfotase alfa concentrations supports weight-based dosing because body weight is a major covariate of asfotase alfa clearance.
- The formulation concentration had an impact on the systemic exposure of asfotase alfa in HPP patients.
- The higher concentration formulation (80 mg/0.8 mL vial) achieved an approximately 25% lower systemic asfotase alfa exposure (i.e., concentrations and AUC) compared to the lower concentration formulations (18 mg/0.45 mL, 28 mg/0.7 mL or 40 mg/mL vials) at the same dose of Asfotase alfa.
- Formation of anti-drug antibodies resulted in reduced systemic exposure of asfotase alfa.

## Nonclinical Toxicology

### Carcinogenesis, Mutagenesis, Impairment of Fertility
- Long-term studies in animals to evaluate carcinogenic potential or studies to evaluate mutagenic potential have not been performed with asfotase alfa.
- Asfotase alfa at intravenous doses up to 50 mg/kg/day administered daily in pregnant rats (approximately 21 times the human AUC of 65486 ng.h/mL at 2 mg/kg dose administered three times weekly for a 50 kg individual) was found to have no adverse effect on fertility and reproductive performance of male and female rats.

# Clinical Studies

### Perinatal/Infantile-Onset HPP
- Study 1 was a 24-week prospective single-arm trial in 11 patients, 7/11 (64%) were female and 10/11 (91%) were white, aged 3 weeks to 39.5 months with severe perinatal/infantile-onset HPP.
- Severe perinatal/infantile-onset HPP was defined as biochemical, medical history and radiographic evidence of HPP as well as the presence of any of the following: rachitic chest deformity, vitamin B6-dependent seizures, or failure to thrive.
- Ten of 11 patients completed the 24-week trial and continued treatment in the extension phase.
- Nine patients have been treated for at least 216 weeks (54 months) and 4 patients have been treated for over 240 weeks (60 months).
- Patients received Asfotase alfa at 3 mg/kg per week for the first month; subsequently, dose increases up to 9 mg/kg per week were allowed for changes in weight and/or for lack of efficacy.
- All 10 patients required dose increases of up to 6 mg/kg per week or higher; 9 patients increased between 4 and 24 weeks after starting treatment and 1 patient increased after 70 weeks due to suboptimal clinical response.
- One patient's dose was decreased from 9 mg/kg per week to 6 mg/kg per week based on PK data.
- Study 2 was a prospective open-label study in 59 patients, 32/59 (54%) were female and 46/59 (78%) were white, aged 1 day to 78 months with perinatal/ infantile-onset HPP.
- Patients received Asfotase alfa at 6 mg/kg per week for the first 4 weeks.
- Ten patients received dose increases higher than 6 mg/kg per week due to suboptimal clinical response, with dose increases occurring between 8 and 24 weeks after starting treatment.
- The recommended dosage regimen of Asfotase alfa for the treatment of perinatal/infantile-onset HPP is up to 9 mg/kg per week administered subcutaneously as 3 mg/kg three times per week.
- Forty-one patients have been treated for at least 24 weeks (6 months) and 15 patients have been treated for at least 96 weeks (24 months).

### Survival and Ventilation-Free Survival
- Survival and invasive ventilation-free survival were compared in Asfotase alfa-treated patients (Studies 1 and 2) with a historical cohort of untreated patients with similar clinical characteristics (Table 7 and Figure 1).
- In patients who required any form of respiratory support, 21 of 26 (81%) of the treated patients survived through their last assessment (median age at last assessment was 3.2 years of age), versus 1 of 20 (5%) of historical controls.
- Radiographs from 68 Asfotase alfa-treated perinatal/infantile-onset HPP patients, including 64 patients in Studies 1 and 2, and 4 patients in Study 3, were examined to assess HPP-related rickets using the 7-point Radiographic Global Impression of Change (RGI-C) scale.
- Patients with a minimum RGI-C score of +2 were defined as "responders".
- Radiologic improvements could be seen by Month 24; at last assessment, 50/68  treated patients were rated as RGI-C responders.
- No comparative data were available from historical controls.
- The mean time interval between the baseline and last RGI-C assessment was 24 months (range was 1 month to 67 months).
- Eighteen perinatal/infantile-onset HPP patients experienced fractures during the course of treatment. There were insufficient data to determine the effect of Asfotase alfa on fractures.
- Height and weight measurements (as measured by z-scores) were available post-treatment for 72 perinatal/infantile-onset HPP patients, including 68 patients enrolled in Studies 1 and 2, and 4 patients enrolled in Study 3.

### Juvenile-Onset HPP
- Study 3 was a prospective open-label 24-week trial that included 8 juvenile-onset HPP patients and 5 perinatal/ infantile-onset HPP patients, 11/13 (85%) were male and 12/13 (92%) were white; on entry, patients were 6 to 12 years of age.
- All 8 juvenile-onset patients entered the extension study and were treated for at least 48 months.
- At trial entry, patients were randomized to receive Asfotase alfa at 6 mg/kg per week or 9 mg/kg per week.
- Two patients received dose reductions during the primary treatment period, including one patient who experienced a decrease in vitamin B6 levels and one patient who experienced recurrent injection site reactions.
- During the extension phase, the dosing regimen for all patients was initially changed to 3 mg/kg per week.
- Dosing was subsequently increased to 6 mg/kg per week, with no patients requiring doses higher than 6 mg/kg per week.
- The recommended dosage regimen of Asfotase alfa for the treatment of juvenile-onset HPP is 6 mg/kg per week.
- Height and weight measurements (as measured by z-scores) in 8 Asfotase alfa-treated patients were compared with a historical cohort of 32 untreated patients with similar clinical characteristics (Table 9).
- Height and weight data for historical patients were collected from medical records.

### Skeletal Manifestations
- Radiographs from 8 Asfotase alfa-treated patients and 32 historical controls were compared to assess HPP-related rickets using the 7-point RGI-C (Radiographic Global Impression of Change) scale.
- Patients who achieved a RGI-C score of 2 or higher (corresponding to substantial healing of rickets) were classified as being responders to treatment.
- All 8 treated patients were rated as responders by Month 54 of treatment.
- The mean duration between the baseline and last RGI-C assessments for control patients was 56 months (range was 8 to 95 months).
- At last assessment, 2/32 (6%) of control patients were rated as responders.
- Eight of 20 (40%) patients with juvenile-onset HPP experienced new fractures during the course of treatment.
- There were insufficient data to assess the effect of Asfotase alfa on fractures.

### Gait/Mobility
- Gait was assessed using a modified Performance Oriented Mobility Assessment-Gait (MPOMA-G) scale in 8 Asfotase alfa-treated patients at 6 month intervals out to 36 months.
- Mobility was also assessed using the 6 Minute Walk Test (6MWT) in 7 of the 8 patients.
- Step length improved by at least 1 point in either foot in 6/8 patients compared to 1/6 (17%) control patients.
- The proportion of patients who had 6MWT percent predicted values within the normal range for age, sex, and height-matched peers increased from 0/8 patients at baseline to 6/6 patients (100%) by Month 48 and all 6 were also able to walk longer distances at this time point compared to baseline.

# How Supplied
- Asfotase alfa is supplied as a sterile, nonpyrogenic, preservative free, clear, slightly opalescent or opalescent, colorless to slightly yellow aqueous solution; a few small translucent or white particles may be present.
- The product is available as single-use vials in a carton of one (1) or twelve (12) vials at the following strengths:

## Storage
- Asfotase alfa vials must be stored in the original carton until the time of use under refrigerated conditions at 2C to 8C (36F to 46F) and protected from light.
- Once removed from refrigeration, Asfotase alfa should be administered within 1 hour.
- Do not use beyond the expiration date stamped on the carton.
- DO NOT FREEZE OR SHAKE.
- Vials are single-use only. Discard any unused product.

# Images

## Drug Images

## Package and Label Display Panel
PRINCIPAL DISPLAY PANEL - 18MG/0.45 ML VIAL CARTON
NDC 25682-010-12
Rx only
STRENSIQ 
(asfotase alfa) 
Injection
18 mg/0.45 mL
For Subcutaneous Use Only.
Single Use Only. Discard Unused Portion. 
Do not mix or dilute with any solutions.
Must be Refrigerated.
Carton contains twelve (12) single-use
2-mL vials of 18 mg/0.45 mL.

### PRINCIPAL DISPALY PANEL - 28MG/0.7 ML VIAL CARTON
NDC 25682-013-12
Rx only
STRENSIQ 
(asfotase alfa) 
Injection
28 mg/0.7 mL
For Subcutaneous Use Only.
Single Use Only. Discard Unused Portion. 
Do not mix or dilute with any solutions.
Must be Refrigerated.
Carton contains twelve (12) single-use
2-mL vials of 28 mg/0.7 mL.

### PRINCIPAL DISPLAY PANEL - 40MG/ML VIAL CARTON
NDC 25682-016-12
Rx only
STRENSIQ 
(asfotase alfa) 
Injection
40 mg/mL
For Subcutaneous Use Only.
Single Use Only. Discard Unused Portion. 
Do not mix or dilute with any solutions.
Must be Refrigerated.
Carton contains twelve (12) single-use
2-mL vials of 40 mg/mL.

### PRINCIPAL DISPLAY PANEL - 80 MG/0.8 ML VIAL CARTON
NDC 25682-019-12
Rx only
STRENSIQ 
(asfotase alfa) 
Injection
80 mg/0.8 mL
For Subcutaneous Use Only.
For patients 40 kg and greater.
Single Use Only. Discard Unused Portion. 
Do not mix or dilute with any solutions.
Must be Refrigerated.
Carton contains twelve (12) single-use
2-mL vials of 80 mg/0.8 mL.

# Patient Counseling Information
- Advise the patient to read the FDA-approved patient labeling (Patient Labeling and Instructions for Use).
- Advise patients or caregivers of the following:

### Preparation
- 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.
- Inspect the solution in the vial(s) for particulate matter and discoloration.
- Assemble injection supplies.
- Administer Asfotase alfa using sterile disposable syringes and injection needles.
- The syringes should be of small enough volume that the prescribed dose can be withdrawn from the vial with reasonable accuracy.
- Always use a new syringe and needle.
- Remove vial cap, aseptically prepare the vial and insert the syringe into the vial to withdraw the prescribed dose for administration.
- Remove any air bubbles in the syringe and verify the correct dose.

### Administration
- Administer Asfotase alfa within 1 hour upon removal of the vial(s) from refrigeration.
- Rotate the injection site to reduce the risk of lipohypertrophy and injection site atrophy.
- Do NOT administer injections in areas that are reddened, inflamed, or swollen.
- Inject Asfotase alfa subcutaneously into the determined site and properly dispose of the needle.
- Asfotase alfa vials are single use only.
- Discard any unused product.

### Hypersensitivity Reactions
- Reactions related to administration and injection may occur during and after Asfotase alfa treatment.
- Inform patients of the signs and symptoms of hypersensitivity reactions, and have them seek immediate medical care should signs and symptoms occur.

### Lipodystrophy
- Lipohypertrophy (enlargement or thickening of tissue) and localized atrophy (depression in the skin) have been reported at injection sites after several months.
- Follow proper injection technique and rotate injection sites.

### Hypophosphatasia (HPP) Registry
- A registry has been established in order to better understand HPP in the population, and to monitor and evaluate long-term treatment effects of Asfotase alfa.
- Patients and their caregivers should be encouraged to participate and advised that their participation is voluntary and may involve long-term follow-up.
- For more information, visit www.hppregistry.com.

# Precautions with Alcohol
Alcohol-Asfotase alfa interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
STRENSIQ  (asfotase alfa).

# Look-Alike Drug Names
There is limited information regarding Asfotase alfa Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price