Version May 2024
Juvenile-onset hypophosphatasia:
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. The FDA-approved dose is based primarily on studies in pediatric patients; additional studies in adult patients with pediatric-onset hypophosphatasia suggest the labeled dosing is appropriate in adults (Ref).
SubQ: 2 mg/kg 3 times weekly or 1 mg/kg 6 times weekly.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Asfotase alfa: Pediatric drug information")
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 titrate due to lack of efficacy (eg, no improvement in respiratory status, growth, or radiographic findings) 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 (Ref); maximum total weekly dose: 9 mg/kg/week. 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.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Flushing (≤15%)
Dermatologic: Erythema of skin (≤15%), injection site pruritus (juvenile-onset HPP: ≤35%; perinatal/infantile-onset HPP: ≤15%), papule of skin (injection site: ≤23%), rash at injection site (≤23%), urticaria at injection site (≤23%)
Endocrine & metabolic: Ectopic calcification (juvenile-onset HPP: 55% perinatal/infantile-onset HPP: 5%), lipodystrophy (juvenile-onset HPP: 70%; perinatal/infantile-onset HPP: 15% to 18%), lipohypertrophy (injection site: 5% to 6%)
Gastrointestinal: Nausea (≤15%), oral hypoesthesia (≤15%), vomiting (3% to 15%)
Hypersensitivity: Anaphylaxis (≤15%), hypersensitivity reaction (10% to 23%)
Immunologic: Immunogenicity (positive for antidrug antibodies: 89%; neutralizing: 57%; presence of antidrug antibodies resulted in reduced systemic exposure of asfotase alfa)
Local: Atrophy at injection site (juvenile-onset HPP: 40%; perinatal/infantile-onset HPP: 6% to 15%), bleeding at injection site (≤23%), bruising at injection site (juvenile-onset HPP: 20%; perinatal/infantile-onset HPP: 9%), cellulitis at injection site (≤23%), erythema at injection site (juvenile-onset HPP: 75%; perinatal/infantile-onset HPP: 23% to 44%), hematoma at injection site (≤23%), hypertrophy at injection site (juvenile-onset HPP: 30%; perinatal/infantile-onset HPP: 8%), induration at injection site (8% to 15%), inflammation at injection site (≤23%), injection site nodule (juvenile-onset HPP: 10%; perinatal/infantile-onset HPP: 3%), injection site reaction (including calcification: ≤90%), injection site scarring (≤23%), itching at injection site (juvenile-onset HPP: ≤35%; perinatal/infantile-onset HPP: ≤15%), pain at injection site (juvenile-onset HPP: ≤40%; perinatal/infantile-onset HPP: ≤15%), residual mass at injection site (≤23%), skin discoloration at injection site (including hyperpigmentation and macules: Juvenile-onset HPP: ≤40%; perinatal/infantile-onset HPP: ≤17%), swelling at injection site (juvenile-onset HPP: 30%; perinatal/infantile-onset HPP: 12%), tenderness at injection site (juvenile-onset HPP: ≤40%; perinatal/infantile-onset HPP: ≤15%), warm sensation at injection site (≤23%)
Nervous system: Chills (≤15%), headache (≤15%), irritability (≤15%), pain (≤15%)
Neuromuscular & skeletal: Muscle rigidity (≤15%)
Miscellaneous: Fever (≤10%)
<1%:
Endocrine & metabolic: Hypocalcemia, pyridoxine deficiency
Hepatic: Chronic active hepatitis
Renal: Nephrolithiasis
Postmarketing:
Dermatologic: Pruritus, skin rash
Local: Lipoatrophy at injection sit
Ophthalmic: Calcific conjunctivitis, corneal changes (calcification)
Renal: Calcium nephrolithiasis
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.
Concerns related to adverse effects:
• Antibody formation/immune-mediated effects: The presence of antibodies has been reported in 89% of treated patients in clinical trials; 57% of these patients showed the presence of neutralizing antibodies. Formation of anti-drug antibody results in a reduced systemic exposure of asfotase alfa and suggests possible immune-mediated effects resulting in disease progression (effect of antibody formation on long-term efficacy is unknown). Consider anti-asfotase alfa antibody testing in patients with progression of symptoms or worsening of disease associated laboratory and imagining biomarkers after a period of initial therapeutic response (contact Strensiq Medical Information at 1-888-765-4747 or [email protected]).
• Ectopic calcifications: Ectopic calcification of the eye, including the cornea and conjunctiva, and the kidneys (nephrocalcinosis, nephrolithiasis) 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, 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: High serum alkaline phosphatase (ALP) levels are expected and reflect circulating asfotase alfa; serum ALP measurements should not be used to make clinical decisions during asfotase alfa treatment.
Craniosynostosis associated with increased intracranial pressure in some cases and worsening of preexisting craniosynostosis has been reported in clinical trials in patients <5 years of age; causality with asfotase alfa has not been established due to insufficient data; craniosynostosis is frequently reported (61.3%) in patient with hypophosphatasia as manifestation of the condition. Monitor (eg, fundoscopy) patients <5 years of age periodically (Strensiq prescribing information [European Medicines Agency] 2015).
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]
No
Solution (Strensiq Subcutaneous)
18 mg/0.45ml (per 0.45 mL): $1,544.40
28 mg/0.7 mL (per 0.7 mL): $2,402.40
40 mg/mL (per mL): $3,432.00
80 mg/0.8 mL (per 0.8 mL): $6,864.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
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]
SubQ: For subcutaneous administration only in the abdominal area, thigh, deltoid, or buttocks. Do not shake. Allow unopened vials to reach room temperature (~15 to 30 minutes) prior to administration; do not warm in microwave or hot water; administer within 3 hours 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). Use of 2 different gauge needles is recommended; 25 gauge to withdraw medication from the vial and 29 gauge for administration. For doses >1 mL, split the volume equally between 2 syringes, and administer 2 injections using separate injection sites.
SubQ: For subcutaneous administration only in the abdominal area, thigh, deltoid, or buttocks. Do not shake. Allow unopened vials to reach room temperature (~15 to 30 minutes) prior to administration; do not warm in microwave or hot water; administer within 3 hours 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.
Note: In pediatric patients <40 kg, do not use the 80 mg/0.8 mL vial; systemic exposure of asfotase alfa achieved with this higher concentration (80 mg/0.8 mL) is lower than that achieved with the other vial strengths which have a lower concentration. A lower exposure may not be adequate for this subgroup of patients.
Hypophosphatasia: Treatment of perinatal/infantile- and juvenile-onset hypophosphatasia (HPP)
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Adverse events have not been observed in animal reproduction studies.
It is not known if asfotase alfa is excreted in breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure, the benefits of breast-feeding to the infant, and the benefits of treatment to the mother.
Hypersensitivity reaction; signs and symptoms of ophthalmic and renal ectopic calcifications and for changes in vision or renal function; serum calcium, PTH, serum phosphate, 25-hydroxyvitamin D; periodic evaluations for craniosynostosis (including fundoscopy) in patients <5 years of age.
Additional recommended patient assessments are based on patient age and include monitoring of biochemistry, skeletal radiographs, respiratory function, growth, pain, mobility and motor function, and quality of life (Kishnani 2017).
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.
Onset of action: Reduction in plasma tissue-nonspecific alkaline phosphatase (TNSALP): After 6 to 12 weeks of treatment
Bioavailability: Age range: 1 day to 66 years: Subcutaneous: 60.2%
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
Time to peak serum concentration:
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)
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