Asfotase alfa

Asfotase alfa is an enzyme replacement medicine that is used to treat hypophosphatasia (HYE-poe-FOS-fa-TAY-zha).

Hypophosphatasia is a rare genetic disorder in which there is a deficiency of an enzyme that helps the body process calcium and phosphorus. This leads to abnormal growth and development of the bones and teeth, including soft or brittle bones, growth problems, and tooth loss.

Asfotase alfa may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use asfotase alfa if you are allergic to it.

Before you use asfotase alfa, tell your doctor about all your medical conditions or allergies.

Your name may be listed on a patient registry while you are using asfotase alfa. This is to track and evaluate any long-term effects of using this medicine.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether asfotase alfa passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Asfotase alfa is part of the drug class:

• Enzymes

It is not known if asfotase alfa crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using asfotase alfa.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Usual Adult Dose for Hypophosphatasia:

Usual dose: 2 mg/kg subcutaneously 3 times per week OR 1 mg/kg subcutaneously 6 times per week
Maximum dose: 9 mg/kg per week

Comments:
-For patients with perinatal/infantile-onset hypophosphatasia (HPP), an increase to 3 mg/kg three times per week may be necessary for insufficient efficacy (e.g., no improvement in respiratory status, growth, or radiographic findings).
-Injection site reactions may limit the tolerability of the 6 times per week dosing regimens.

Use: For the treatment of patients with perinatal/infantile and juvenile onset HPP.

Usual Pediatric Dose for Hypophosphatasia:

Usual dose: 2 mg/kg subcutaneously 3 times per week OR 1 mg/kg subcutaneously 6 times per week
Maximum dose: 9 mg/kg per week

Comments:
-For patients with perinatal/infantile-onset hypophosphatasia (HPP), an increase to 3 mg/kg three times per week may be necessary for insufficient efficacy (e.g., no improvement in respiratory status, growth, or radiographic findings).
-Injection site reactions may limit the tolerability of the 6 times per week dosing regimens.

Use: For the treatment of patients with perinatal/infantile and juvenile onset HPP.

• 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

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.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Irritation where the shot is given.
• Change in skin color where the shot was given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

There are no known significant interactions.

Commonly reported side effects of asfotase alfa include: anaphylaxis, ectopic calcification, nausea, calcium nephrolithiasis, fever, headache, hypersensitivity reaction, lipodystrophy, vomiting, chills, erythema, flushing, and irritability. See below for a comprehensive list of adverse effects.

Applies to asfotase alfa: parenteral injection

Side effects include:

Injection site reactions, ectopic calcifications, lipodystrophy, hypersensitivity reactions.

Data not available

Data not available

In animal studies in rats and rabbits, IV use during the period of organogenesis showed no evidence of fetotoxicity, embryolethality, or teratogenicity at doses of 21 and 24 times the recommended human exposure dose, respectively. Following subcutaneous administration in pregnant mice, cross-placental transfer of drug was observed. There are no data in pregnant women. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Safety has not been established during pregnancy US FDA pregnancy category: Not assigned Risk summary: No data available on use of this drug in pregnant women to inform a drug-related risk. Comments: This drug is not recommended in the UK for use during pregnancy or in women of childbearing potential not using contraception.