Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous [preservative free]:
Strensiq: 18 mg/0.45 mL (0.45 mL); 28 mg/0.7 mL (0.7 mL); 40 mg/mL (1 mL); 80 mg/0.8 mL (0.8 mL) [contains mouse (murine) and/or hamster protein]
Pharmacology
Mechanism of Action
Asfotase alfa is a human recombinant tissue-nonspecific alkaline phosphatase-Fc-deca-aspartate fusion protein with enzymatic activity that promotes bone mineralization in patients with hypophosphatasia.
Pharmacokinetics/Pharmacodynamics
Onset of Action
Reduction in plasma TNSALP substrates: After 6 to 12 weeks of treatment
Time to Peak
Infants and Children ≤5 years: ~15 hours (range: 0 to 32.2 hours)
Children > 5 to 12 years: ~ 21 hours (range: 12 to 32.2 hours)
Half-Life Elimination
~5 days (based on data from 38 patients, ages undefined); in 60 patients aged 1 day to 66 years (n=45 pediatric patients): ~2.3 days
Use: Labeled Indications
Hypophosphatasia: Treatment of perinatal/infantile- and juvenile-onset hypophosphatasia (HPP)
Contraindications
There are no contraindications listed in the manufacturer’s labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to asfotase alfa or any component of the formulation.
Dosage and Administration
Dosing: Adult
Hypophosphatasia (HPP): SubQ: Note: Round patient weight to the nearest kg when determining dose. Injection-site reactions may limit the tolerability of the 6 times per week regimen:
Juvenile-onset HPP: 2 mg/kg 3 times weekly or 1 mg/kg 6 times weekly.
Dosing: Pediatric
Note: Round patient weight to the nearest kg when determining dose. Do not administer the 80 mg/0.8 mL concentration vial to pediatric patients weighing <40 kg; exposure is less than what is achieved with lower concentration vials.
Perinatal/infantile-onset hypophosphatasia (HPP): Infants, Children, and Adolescents: SubQ: 6 mg/kg/week administered as either 2 mg/kg/dose 3 times weekly or 1 mg/kg/dose 6 times weekly; may increase dose up to 9 mg/kg/week administered as 3 mg/kg/dose 3 times weekly; in clinical trials, dose increases were considered after at least 4 weeks of therapy (Whyte 2012; Whyte 2016); maximum total weekly dose: 9 mg/kg/week. Note: Lack of clinical response may be defined as no improvement in respiratory status, growth, or radiographic findings. Injection site reactions may limit the tolerability of the 6-times-per-week regimen.
Juvenile-onset hypophosphatasia (HPP): Children and Adolescents: SubQ: 6 mg/kg/week administered as either 2 mg/kg/dose 3 times weekly or 1 mg/kg/dose 6 times weekly. Injection site reactions may limit the tolerability of the 6-times-per-week regimen.
Administration
SubQ: For subcutaneous administration only in the abdominal area, thigh, or deltoid. Administer within 1 hour upon removal from refrigerator. Rotate the injection sites to reduce the risk of lipodystrophy. Do not administer injections in areas that are reddened, inflamed, or swollen. Solution is clear, slightly opalescent or opalescent, colorless to slightly yellow; few small translucent or white particles may be present; discard vial(s) not consistent with this appearance. Administer with 1 mL syringe with 1/2 inch needle (25 to 29 gauge). For doses >1 mL, split the volume equally between 2 syringes, and administer 2 injections using separate injection sites.
Storage
Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton and protect from light. Once removed from refrigerator, administer within 1 hour. Do not freeze or shake. Discard any unused product.
Drug Interactions
There are no known significant interactions.
Test Interactions
Asfotase alfa interferes with alkaline phosphatase (ALP)-conjugated test systems (commonly used to measure hormones, bacterial antigens, and antibodies) rendering erroneous test results. Alternative laboratory assays that do not utilize ALP-conjugate technology are recommended in patients receiving asfotase alfa.
Adverse Reactions
Endocrine & metabolic: Ectopic calcification (includes calcification of the cornea, conjunctiva, and kidneys; 55%, juvenile-onset HPP; ≤5% perinatal/infantile-onset HPP), lipodystrophy (≤6%)
Hypersensitivity: Hypersensitivity reaction (10% to 23%)
Immunologic: Immunogenicity (positive for antidrug antibodies: 78%; neutralizing: 45%; presence of antidrug antibodies resulted in reduced systemic exposure of asfotase alfa)
Local: Erythema at injection site (juvenile-onset HPP: 75%; perinatal/infantile-onset HPP: 23% to 44%), atrophy at injection site (juvenile-onset HPP: 40%; perinatal/infantile-onset HPP: 6% to 15%), skin discoloration at injection site (including macules: Juvenile-onset HPP: 35% to 40%; perinatal/infantile-onset HPP: ≤17%), pain at injection site (juvenile-onset HPP: ≤40%; perinatal/infantile-onset HPP: ≤8% to ≤15%), tenderness at injection site (juvenile-onset HPP: ≤40%; perinatal/infantile-onset HPP: ≤15%), itching at injection site (juvenile-onset HPP: 35%; perinatal/infantile-onset HPP: ≤15%), hypertrophy at injection site (juvenile-onset HPP: 30%; perinatal/infantile-onset HPP: ≤8%), swelling at injection site (juvenile-onset HPP: 30%; perinatal/infantile-onset HPP: ≤12%), injection site reaction (≤23%; including rash, nodule, papule, inflammation, hemorrhage, hematoma, calcification, mass, scar, cellulitis, or not otherwise defined), bruising at injection site (juvenile-onset HPP: 20%; perinatal/infantile-onset HPP: ≤9%), induration at injection site (8% to 15%)
<1%, postmarketing, and/or case reports: Chronic active hepatitis, hypocalcemia, nephrolithiasis, pyridoxine deficiency
Warnings/Precautions
Concerns related to adverse effects:
- Antibody formation: The presence of antibodies has been reported in 78% of treated patients in clinical trials. Approximately 45% of these patients showed the presence of neutralizing antibodies. Formation of anti-drug antibody results in a reduced systemic exposure of asfotase alfa.
- Ectopic calcifications: Ectopic calcification of the eye, including the cornea and conjunctiva, and the kidneys (nephrocalcinosis) have been reported; there is insufficient information to determine if these events were consistent with the disease (patients with hypophosphatasia are at increased risk for developing ectopic calcifications) or due to asfotase alfa. No visual changes or changes in renal function were reported resulting from the occurrence of ectopic calcifications. Eye exams and renal ultrasounds are recommended at baseline and periodically during treatment.
- Hypersensitivity reactions: Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have been reported; symptoms consistent with anaphylaxis, including difficulty breathing, choking sensation, nausea, periorbital edema, and dizziness, have been reported. Reactions may occur within minutes after administration or in patients on treatment for >1 year. Other hypersensitivity reactions (eg, vomiting, fever, headache, flushing, irritability, chills, skin erythema, rash, pruritus, oral hypoesthesia) have also been reported. If a severe hypersensitivity reaction occurs, discontinue treatment and initiate appropriate medical treatment. If the decision is made to re-administer, 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. Ensure proper injection technique and rotate injection sites.
Other warnings/precautions:
- Elevated alkaline phosphatase (ALP): High serum ALP levels are expected and reflect circulating asfotase alfa; serum ALP measurements should not be used to make clinical decisions during asfotase alfa treatment.
Monitoring Parameters
Hypersensitivity reaction; signs and symptoms of ophthalmic and renal ectopic calcifications and for changes in vision or renal function
Pregnancy
Pregnancy Considerations
Adverse events have not been observed in animal reproduction studies.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience injection site irritation or skin discoloration. Have patient report immediately to prescriber choking, nausea, vomiting, eyelid swelling, dizziness, passing out, chills, headache, flushing, irritability, numbness or tingling of the mouth, or injection site skin changes (thick or thin) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
