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Strensiq
Classes
Metabolic Enzyme Therapy, Other
Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Asfotase alfa is a clear, slightly opalescent or opalescent, colorless to slightly yellow aqueous solution; few small translucent or white particles may be present.
NOTE: Do not use the 80 mg/0.8 mL vial of asfotase alfa in pediatric patients weighing less than 40 kg. 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 concentrations). A lower exposure may not be adequate for this subgroup of patients.
Remove unopened vial(s) from refrigerator 15 to 30 minutes prior to injection to allow liquid to reach room temperature. Do NOT warm vials (e.g. do not warm in a microwave or hot water). Do NOT shake.
Use solution as supplied; no dilution necessary.
Using a sterile 1 mL syringe and 1/2 inch needle (e.g., 25 gauge), withdraw solution from vial to provide prescribed dose. Use the smaller bore needle (e.g., 29 gauge) to administer the injection.
When preparing a volume for injection that is greater than 1 mL, split the volume equally between 2 syringes, and administer 2 injections at 2 separate sites. Always use a new syringe and needle.
Administer by subcutaneous injection into the abdominal area, thigh, deltoid, or buttocks. Rotate the injection site to reduce the risk of lipodystrophy.
Do not administer injections in areas that are reddened, inflamed, or swollen.
Administer asfotase alfa within 3 hours upon removal of the vial(s) from refrigeration.
Storage: Asfotase vials are single use only; discard any unused product.
Adverse Reactions
anaphylactoid reactions / Rapid / 1.0-1.0
antibody formation / Delayed / 78.0-78.0
erythema / Early / 41.0-75.0
lipodystrophy / Delayed / 18.0-70.0
ectopic calcification / Delayed / 4.0-55.0
hepatitis / Delayed / 0-1.0
hypocalcemia / Delayed / 0-1.0
nephrolithiasis / Delayed / 0-1.0
hematoma / Early / Incidence not known
injection site reaction / Rapid / 56.0-90.0
skin hypopigmentation / Delayed / 15.0-40.0
pruritus / Rapid / 0-10.0
vomiting / Early / 5.0-10.0
hypoesthesia / Delayed / Incidence not known
chills / Rapid / Incidence not known
headache / Early / Incidence not known
irritability / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
flushing / Rapid / Incidence not known
rash / Early / Incidence not known
nausea / Early / Incidence not known
dizziness / Early / Incidence not known
fever / Early / Incidence not known
Common Brand Names
Strensiq
Dea Class
Rx
Description
Tissue nonspecific alkaline phosphatase (TNSALP)
Used for treatment of perinatal/infantile- and juvenile-onset hypophosphatasia (HPP)
Ectopic calcification of the eyes and kidneys can occur; eye exam and renal ultrasound recommended at baseline and periodically during treatment
Dosage And Indications
2 mg/kg/dose subcutaneously 3 times/week or 1 mg/kg/dose subcutaneously 6 times/week. Injection site reactions may limit the tolerability of the 6 times/week regimen. For perinatal/infantile-onset HPP, the dose may be increased to 3 mg/kg/dose subcutaneously 3 times/week for insufficient efficacy (e.g., no improvement in respiratory status, growth, or radiographic findings).
Dosing Considerations
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
There are no drug interactions associated with Asfotase alfa products.
How Supplied
Asfotase alfa/Strensiq Subcutaneous Inj Sol: 0.45mL, 0.7mL, 0.8mL, 1mL, 18mg, 28mg, 40mg, 80mg
Maximum Dosage
6 mg/kg/week subcutaneously for juvenile-onset HPP; 9 mg/kg/week subcutaneously for perinatal/infantile-onset HPP.
Mechanism Of Action
Hypophosphatasia (HPP) is caused by mutations in the tissue nonspecific alkaline phosphatase (TNSALP) enzyme, which is encoded by the alkaline phosphatase (ALP) gene. When a mutation of this gene occurs, the protein product may be faulty, inefficient, or absent. TNSALP is necessary for the proper development and mineralization of bones and teeth and is expressed in the liver and kidneys as well as bone. Mutations in the ALPL gene result in insufficient levels of functional TNSALP, which, in turn, leads to the accumulation of several TNSALP substrates, including phosphoethanolamine, pyridoxal 5'-phosphate, and inorganic pyrophosphate (PPi), which help to regulate bone mineralization. Elevated extracellular levels of PPi block hydroxyapatite crystal growth which inhibits bone mineralization and causes an accumulation of unmineralized bone matrix resulting in rickets and bone deformation in infants and children and as osteomalacia once growth plates close, along with muscle weakness. TNSALP enzyme activity correlates with disease severity, usually less residual enzyme activity correlates with more severe disease. Asfotase alfa therapy replaces the TNSALP enzyme and reduces the elevated enzyme substrate levels. By reducing the elevated substrate levels, the body's ability to mineralize bone is improved.
Pharmacokinetics
Asfotase alfa is administered as a subcutaneous injection. Its pharmacokinetics exhibit dose proportionality across the dose range of 0.3 to 3 mg/kg and appear to be time-dependent. Steady state exposure is achieved as early as 3 weeks after the first dose is administered. The elimination half-life after subcutaneous administration is approximately 5 days. Weight is a major covariate of asfotase alfa clearance and product formulation concentration impacts the systemic exposure of asfotase alfa in HPP patients. The 80 mg/0.8 mL concentration achieves approximately 25% lower systemic asfotase alfa exposure (i.e., concentrations and AUC) compared to the 18 mg/0.45 mL concentration at the same dose. Formation of anti-drug antibodies result in reduced systemic exposure of asfotase alfa.
Perinatal/infantile- and juvenile-onset HPP patients treated with asfotase alfa had reductions in plasma tissue nonspecific alkaline phosphatase (TNSALP) substrates inorganic pyrophosphate (PPi) and pyridoxal 5-phosphate (PLP) within 6 to 12 weeks of treatment. However, reductions in plasma PPi and PLP concentrations 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.
Pregnancy And Lactation
There are no available data regarding use asfotase alfa during pregnancy to inform a drug-associated risk. Animal data did not reveal evidence of impaired fertility or harm to the fetus when administered at doses causing plasma exposures up to 21 and 24 times, respectively, the exposure at the recommended human dose.
There are no data on the presence of asfotase alfa in human milk, the effects on a breast-fed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.