to 15 [40:1 year. 1 If severe hypersensitivity reaction occurs, discontinue asfotase alfa and initiate appropriate treatment. 1 Consider risks and benefits of retreatment following severe hypersensitivity reaction; if retreatment instituted, monitor for signs and symptoms of severe hypersensitivity reaction. 1 Lipodystrophy Localized lipodystrophy (e.g., lipoatrophy, lipohypertrophy) reported at injection sites following several months of therapy. 1 Advise patients to follow proper injection technique and rotate injection sites to prevent such occurrence. 1 Ectopic Calcifications Ectopic calcification of the eye (including cornea, conjunctiva) and kidney (nephrocalcinosis) reported in 14% of patients in clinical trials. 1 Reported cases were not associated with changes in vision or renal function. 1 Patients with HPP are at increased risk for developing ectopic calcifications. 1 Not known whether asfotase alfa treatment contributed to occurrence of ectopic calcification. 1 Ophthalmologic examinations and renal ultrasound recommended at baseline and periodically during therapy. 1 Injection Site Reactions Injection site reactions (e.g., erythema, discoloration/hypopigmentation, pain/tenderness, pruritus, swelling, induration, macules, bruising, nodules) reported in 63% of patients. 1 Incidence of such reactions higher in patients with juvenile-onset HPP than in those with perinatal/infantile-onset HPP. 1 Antibody Formation Anti-drug antibodies reported in 78% of patients; neutralizing antibodies also reported in 45% of these patients. 1 No correlation observed between anti-drug antibody titer and neutralizing antibody (percent inhibition) values. 1 Formation of anti-drug antibody resulted in reduced systemic exposure of asfotase alfa. 1 Specific Populations Pregnancy No adequate and well-controlled studies in pregnant women. 1 No evidence of fetotoxicity, embryolethality, or teratogenicity in animals. 1 Lactation Not known whether distributed into human milk. 1 Effects of drug on milk production or on breast-fed infant also unknown. 1 Consider known benefits of breast-feeding along with mother's clinical need for asfotase alfa and any potential effects of drug or disease on the infant. 1 Pediatric Use Most patients (90%) included in clinical trials were pediatric patients 1 day to 16 years of age. 1 Geriatric Use No experience in patients 65 years of age; not known whether geriatric patients respond differently than younger patients. 1 Common Adverse Effects Injection site reactions, 1 4 ectopic calcifications, 1 lipodystrophy, 1 hypersensitivity reactions. 1 Interactions for Asfotase Alfa No formal drug interaction studies to date. 1 Asfotase Alfa Pharmacokinetics Absorption Bioavailability Approximately 62% following sub-Q administration. 3 Steady-state exposure achieved as early as 3 weeks. 1 Concentration of asfotase alfa injection affects drug exposure; at same dosage, exposure approximately 25% lower with 100-mg/mL concentration compared with 40-mg/mL concentration. 1 3 Time to peak plasma concentrations following multiple sub-Q doses of 2 mg/kg 3 times weekly in patients with HPP approximately 15 or 21 hours in patients 5 years of age or those >5 to 12 years of age, respectively. 1 Pharmacokinetics dose-proportional across dosage range of 0.3 3 mg/kg. 1 Formation of anti-drug antibodies reduces systemic exposure of asfotase alfa. 1 Distribution Extent Not known whether distributed into human milk. 1 Elimination Half-life Approximately 5 days. 1 Stability Storage Parenteral Injection 2 8 C. 1 Protect from light; store in original carton until time of use. 1 Do not freeze or shake. 1 Administer within 1 hour after removal from refrigeration. 1 Actions Biosynthetic (recombinant DNA origin) form of human TNSALP, a metalloenzyme that catalyzes hydrolysis of phosphomonoesters. 1 3 4 5 6 7 Specific activity of asfotase alfa is 620 1250 units/mg, with 1 unit defined as amount of asfotase alfa that results in formation of 1 mcmol of p -nitrophenol from p -nitrophenyl phosphate per minute at 37 C. 1 Provides exogenous source of TNSALP, reducing accumulation of TNSALP substrates, promoting bone mineralization, and improving skeletal structure. 1 6 Advice to Patients Importance of advising patients and their caregivers to read the manufacturer's patient information and instructions for use. 1 Importance of instructing patients and/or caregiver regarding proper dosage, preparation, and administration of asfotase alfa, including use of aseptic technique and safe disposal of needles and syringes. 1 (See Dosage and Administration.) When volume for injection >1 mL, importance of dividing the volume equally between 2 syringes and injecting into separate sites. 1 Importance of rotating injection sites and avoiding areas that are reddened, inflamed, or swollen. 1 Risk of injection site reactions and other administration-associated adverse reactions (e.g., erythema, discoloration/hypopigmentation, pain/tenderness, pruritus, swelling, induration, macules, bruising, nodules). 1 Importance of informing patients of signs and symptoms of hypersensitivity reactions (difficulty breathing, nausea, periorbital edema, dizziness); advise patients to seek immediate medical care if such symptoms occur. 1 Risk of lipodystrophy and localized atrophy at injection sites. 1 Importance of following proper injection technique and rotating injection sites. 1 Importance of informing patients of the HPP registry established to monitor variability and progression of HPP and long-term effects of asfotase alfa. 1 Importance of encouraging patient participation in this voluntary program and of advising patients that participation may involve long-term follow-up. 1 (See Hypophosphatasia under Uses.) Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs. 1 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Asfotase Alfa Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, for subcutaneous use only 40 mg/mL (18, 28, and 40 mg) Strensiq Alexion 100 mg/mL (80 mg) Strensiq Alexion AHFS DI Essentials. Copyright 2017, Selected Revisions February 21, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Alexion Pharmaceuticals, Inc. Strensiq (asfotase alfa) injection prescribing information. Cheshire, CT; 2016 Oct. 2. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2016 Sep 6. 3. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 125513Orig1s000: Summary Review: From FDA website. Accessed 2016 Sep. 4. Whyte MP, Greenberg CR, Salman NJ et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med . 2012; 366:904-13. [PubMed 22397652] 5. Whyte MP, Rockman-Greenberg C, Ozono K et al. Asfotase alfa treatment improves survival for perinatal and infantile hypophosphatasia. J Clin Endocrinol Metab . 2016; 101:334-42. [PubMed 26529632] 6. Scott LJ. Asfotase alfa: a review in paediatric-onset hypophosphatasia. Drugs . 2016; 76:255-62. [PubMed 26744272] 7. Orimo H. Pathophysiology of hypophosphatasia and the potential role of asfotase alfa. Ther Clin Risk Manag . 2016; 12:777-86. [PubMed 27274262] 8. Alexion Pharmaceuticals, New Haven, CT: Personal communication. Next Pregnancy Warnings Print this page Add to My Med List More about asfotase alfa Side Effects During Pregnancy Dosage Information Support Group En Español 0 Reviews Add your own review/rating Drug class: miscellaneous metabolic agents Consumer resources Asfotase alfa Professional resources Asfotase Alfa (Wolters Kluwer) Other brands: Strensiq Related treatment guides Hypophosphatasia]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Drug Class Miscellaneous metabolic agents Related Drugs Hypophosphatasia Strensiq , More... 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