Asfotase alfa

Get emergency medical help if you have signs of an allergic reaction: hives; dizziness, nausea, vomiting; difficult breathing; swelling of your face, lips, tongue, or throat.

Common side effects may include:

• pain, itching, swelling, redness, bruising, hardening, pitting, or other skin changes where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Do not inject this medicine into skin areas that are red or swollen.

Other drugs may interact with asfotase alfa, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

• Store asfotase alfa in the original carton in the refrigerator.
• Keep asfotase alfa vials away from light until you are about to use it.
• Use asfotase alfa within one hour of removing it from the refrigerator.
• Do not freeze or shake asfotase alfa vials.
• Asfotase alfa vials are single-use vials; throw away any unused product.

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 usually given 3 to 6 times per week. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Asfotase alfa is injected under the skin. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

You may need to use 2 vials and 2 separate syringes to make up a single dose of this medicine. Follow your doctor's dosing instructions very carefully.

Your care provider will show you the best places on your body to inject asfotase alfa. Use a different place each time you give an injection. Do not inject into the same place two times in a row.

Do not use asfotase alfa if it has changed colors or has particles in it. Call your pharmacist for new medication.

Each single-use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

While using asfotase alfa, you may need frequent eye examinations.

Tell your doctor if you have any changes in weight. Asfotase alfa doses are based on weight (especially in children), and any changes may affect the dose.

Store vials in the original container in a refrigerator, protected from light. Do not freeze or shake this medicine.

You may take the medicine out of the refrigerator and allow it to reach room temperature before preparing a dose. Do not leave the medicine at room temperature for longer than 1 hour.

Contraindications

• Manufacturer states none known.1

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis) reported.1 3 Manifestations included vomiting, fever, headache, flushing, irritability, chills, erythema, rash, pruritus, oral hypoesthesia, signs and symptoms consistent with anaphylaxis (e.g. difficulty breathing, choking sensation, nausea, periorbital edema, dizziness).1 May occur within minutes following injection and in patients receiving therapy for >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

No adequate and well-controlled studies in pregnant women.1

No evidence of fetotoxicity, embryolethality, or teratogenicity in animals.1

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

Most patients (90%) included in clinical trials were pediatric patients 1 day to 16 years of age.1

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

No formal drug interaction studies to date.1

(AZ fo tase AL fa)

Asfotase alfa is a human recombinant tissue-nonspecific alkaline phosphatase-Fc-deca-aspartate fusion protein with enzymatic activity that promotes bone mineralization in patients with hypophosphatasia.

Hypophosphatasia (HPP): SubQ: Note: Round patient weight to the nearest kg when determining dose. Do not administer the 80 mg/0.8 mL concentration vial to pediatric patients weighing <40 kg; exposure is less than what is achieved with lower concentration vials. Injection-site reactions may limit the tolerability of the 6 times per week regimen:

Perinatal/infantile-onset HPP: Infants, Children, and Adolescents: 2 mg/kg 3 times weekly or 1 mg/kg 6 times weekly. May increase dose for lack of efficacy (eg, no improvement in respiratory status, growth, or radiographic findings) up to 3 mg/kg 3 times weekly (maximum: 9 mg/kg per week).

Juvenile-onset HPP: Children and Adolescents: 2 mg/kg 3 times weekly or 1 mg/kg 6 times weekly.

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 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.

Data not available