General

Pronunciation:
az-fo-tase al-fa

Trade Name(s)

• Strensiq

Ther. Class.

none assigned

Pharm. Class.

enzymes

Indications

Perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).

Action

As a recombinant form of tissue nonspecific alkaline phosphatase, it promotes bone mineralization.

Therapeutic Effect(s):

Improved survival in patients with perinatal/infantile-onset HPP; improved growth and mobility in patients with juvenile-onset HPP.

Pharmacokinetics

Absorption: 60% absorbed after SUBQ administration.

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: 5 days.

TIME/ACTION PROFILE (reduction in plasma tissue nonspecific alkaline phosphatase substrates)

Contraindication/Precautions

Contraindicated in:

• None.

Use Cautiously in:

• OB:   Safety not established in pregnancy;
• Lactation:  Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.

Adverse Reactions/Side Effects

EENT: ectopic calcification of eye

GU: ectopic calcification of kidney

Metabolic: lipodystrophy

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis), injection site reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None known.

Route/Dosage

Perinatal/Infantile-Onset HPP

SUBQ (Neonates and Infants): 2 mg/kg 3 times weekly  or  1 mg/kg 6 times weekly; if suboptimal response, may ↑ to 3 mg/kg 3 times weekly.

SUBQ (Children ≤16 yr): 2 mg/kg 3 times weekly or  1 mg/kg 6 times weekly.

Availability

Solution for injection: 18 mg/0.45 mL, 28 mg/0.7 mL, 40 mg/mL, 80 mg/0.8 mL

Assessment

• Assess for signs and symptoms of HPP (biochemical, medical history, and radiographic evidence of HPP, as well as presence of any of the following: rachitic chest deformity, vitamin B6–dependent seizures, or failure to thrive) prior to therapy.
• Monitor for signs and symptoms of hypersensitivity reactions (difficulty breathing, choking sensation, nausea, periorbital edema, dizziness, vomiting, fever, headache, flushing, irritability, chills, erythema, rash, pruritus, oral hypoesthesia). If anaphylactic or severe hypersensitivity reactions occur, immediately discontinue, and start emergency treatment. Consider the risks and benefits of readministering following severe hypersensitivity reactions.
• Obtain baseline ophthalmalogic exams and renal ultrasounds periodically during therapy to monitor for calcifications leading to visual changes and decreased renal function.

Lab Test Considerations:

Inform lab that asfotase alfa interferes with alkaline phosphatase testing. High serum alkaline phosphatase levels are expected and reflect circulating concentrations of asfotase alfa. Do not use alkaline phosphatase levels for clinical decisions.

Implementation

• SUBQ Remove from the refrigerator 15–30 min before injecting to allow the liquid to reach room temperature (do not warm any other way). Prepare dose using 1 mL syringes and ½-inch needles, 25–29 gauge. See manufacturer's guidelines for dose preparation. If >1 mL, split volume equally between 2 syringes, and administer 2 injections in 2 separate sites. Solution is clear, colorless to slightly yellow, opalescent or slightly opalescent, with few translucent or white particles. Discard any vial(s) not consistent with this appearance. Do not shake vials. Remove air bubbles from syringe. Pinch skin and inject at 90° angle; for patients with little fat, use 45° angle. Rotate sites between abdomen, upper arms, and upper legs to prevent lipodystrophy. Do not inject into areas that are hot, red, or swollen. Administer within 3 hr upon removal of the vial(s) from refrigeration; do not freeze. Vials are one time use only. Discard any unused product. Protect from light.
• Administer in a health care setting with appropriate medical monitoring and supportive measures (cardiopulmonary resuscitation equipment) available during administration.

Patient/Family Teaching

• Explain purpose and side effects of asfotase alfa to patient and/or caregiver.
• Advise patient and/or caregiver to read Patient Information  before starting therapy.
• Advise patient and/or caregiver to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
• Instruct patient and/or caregiver if a dose is missed, take as soon as remembered. If it is close to the time of the next dose, skip the missed dose and go back to the normal time. Do not give simultaneous double or extra doses.
• Teach patient and/or caregiver the signs and symptoms of an hypersensitivity reaction; if any occur, seek immediate medical care.
• Advise patients and/or caregiver to monitor for skin thickening or pits at injection sites. Rotate injection sites to prevent lipodystrophy.
• Explain need for eye and kidney exams periodically during therapy to patient and/or caregiver.
• Encourage patient and/or caregiver to enroll patient in the Hypophosphatasia (HPP) Registry to better understand HPP and monitor long-term progress of patients. Participation is voluntary at www.hppregistry.com.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

• Improved survival in patients with perinatal/infantile-onset HPP.
• Improved growth and mobility in patients with juvenile-onset HPP.