Dosing & Uses
Dosage Forms & Strengths
SC injectable solution
- 80 mg/0.8mL (use for patients who weigh >40kg)
Hypophosphatasia
Indicated for perinatal/infantile- and juvenile-onset hypophosphatasia (HPP)
6 mg/kg/week SC administered as 2 mg/kg given 3 x/week or 1 mg/kg given 6 x/week
Injection site reactions may limit the tolerability of the 6 x/week regimen
Note: For perinatal/infantile-onset HPP, the dose may be increased for lack of efficacy (eg, no improvement in respiratory status, growth, or radiographic findings) up to 9 mg/kg per week administered SC as 3 mg/kg 3 x/week
Dosage Forms & Strengths
SC injectable solution
- 18mg/0.45mL
- 28mg/0.7mL
- 40mg/mL
- 80 mg/0.8mL (use for patients who weigh >40kg)
Hypophosphatasia
Indicated for perinatal/infantile- and juvenile-onset hypophosphatasia (HPP)
6 mg/kg/week SC administered as 2 mg/kg given 3 x/week or 1 mg/kg given 6 x/week
Injection site reactions may limit the tolerability of the 6 x/week regimen
Note: For perinatal/infantile-onset HPP, the dose may be increased for lack of efficacy (eg, no improvement in respiratory status, growth, or radiographic findings) up to 9 mg/kg per week administered SC as 3 mg/kg 3 x/week
Dosing Considerations
Caution: Do not use the 80-mg/0.8 mL vial in pediatric patients weighing <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
Adverse Effects
>10%
Injection site reactions (46-90%)
Lipodystrophy (18-70%)
Ectopic calcifications (5-55%)
1-10%
Vomiting/emesis (3-10%)
Systemic hypersensitivity reactions (2-10%)
Warnings
Contraindications
None
Cautions
Hypersensitivity reactions (rare) reported in clinical trials; reactions have occurred within minutes after subcutaneous administration and have been observed more than 1 year after treatment initiation; monitor and if severe reaction occurs, discontinue treatment and initiate appropriate medical treatment
Localized lipodystrophy, including lipoatrophy and lipohypertrophy, has been reported at injection sites after several months; monitor for proper injection technique and injection site rotation
Patients with HPP are at increased risk for developing ectopic calcifications; in clinical trials, 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 associated with asfotase alfa; ophthalmology examinations and renal ultrasounds are recommended at baseline and periodically during treatment
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; recommended that laboratory assays which do not have ALP- conjugate technology be used when testing samples from patients; inform laboratory personnel that patient is being treated with drug and discuss use of testing platform which does not utilize an ALP-conjugated test system
Pregnancy
Pregnancy
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 IV to pregnant rats and rabbits during the period of organogenesis showed no evidence of fetotoxicity, embryo lethality, or teratogenicity at doses causing plasma exposures up to 21 and 24 times, respectively, the exposure at the recommended human dose
Lactation
Unknown if distributed in human breast milk
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Enzyme replacement that is a soluble glycoprotein composed of 2 identical polypeptide chains; each chain consists of the catalytic domain of human tissue nonspecific alkaline phosphatase (TNSALP), the human immunoglobulin G1 Fc domain and a deca-aspartate peptide used as a bone targeting domain
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
Administration
SC Preparation
Determine the volume needed for the prescribed weight-based dose
- Total dose (mg) = patient’s weight (kg) x prescribed dose (mg/kg)
- Total injection volume (mL) = Total dose (mg) divided by concentration (40 mg/mL or 80 mg/0.8 mL)
- Round total injection volume to the nearest hundredth of a mL
- Total number of vials = Total injection volume divided by vial volume (mL)
- If the volume for injection is >1 mL, split the volume equally between 2 syringes, and administer as 2 SC injections (use separate injection sites)
- See prescribing information for detailed weight-based charts
Prepare the syringe(s)
- Inspect the solution in the vial(s) for particulate matter and discoloration
- Should appear as a clear, slightly opalescent or opalescent, colorless to slightly yellow aqueous solution; few small translucent or white particles may be present
- Discard any vials(s) not consistent with this appearance
- Assemble injection supplies
- Administer using sterile disposable 1-mL syringes and 0.5-inch injection needles, from 25- to 29-gauge
- 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
SC Administration
For SC administration only
Administer within 1 hr 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, or deltoid
Do NOT administer injections in areas that are reddened, inflamed, or swollen
Inject SC into the determined site and properly dispose of the needle
Vials are single use only; discard any unused product
Storage
Store refrigerated 2-8°C (36-46°F)
Store unopened vials in the original carton to protect from light
Do not freeze or shake
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
