Velaglucerase alfa

Pregnancy Category: B

Lactation: Unknown whether distributed in breast milk; use caution

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.

Mechanism of Action

Hydrolytic lysosomal glucocerebroside-specific enzyme plays a role in the hydrolysis of glucocerebroside to glucose and ceramide thereby preventing the accumulation of glucocerebroside in macrophages, which is responsible for the signs and symptoms of Gauche'r disease

Pharmacokinetics

Half-Life: 11-12 min

Vd: 82-108 mL/kg

Clearance:  6.72-7.56 mL/min/kg

Take velaglucerase alfa exactly as prescribed.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take 2 doses of velaglucerase alfa at the same time.

Other drugs may interact with velaglucerase 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.

Contraindications

• No known contraindications.1

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, reported.1

Manage hypersensitivity reactions based on severity.1 If anaphylaxis or other severe hypersensitivity occurs, discontinue velaglucerase alfa immediately and initiate appropriate therapy.1 For mild reactions, may reduce infusion rate, temporarily interrupt infusion, and/or administer antihistamines, antipyretics, and/or corticosteroids.1 Ensure that appropriate medical support is readily available during administration.1

Premedication with antihistamines and/or corticosteroids may prevent subsequent reactions in patients who have experienced a reaction to velaglucerase alfa or other enzyme replacement therapy.1

As with all therapeutic proteins, there is a potential for immunogenicity with velaglucerase alfa therapy.1 Development of IgG antibodies to velaglucerase alfa reported in at least one patient.1 Relationship between such antibodies and hypersensitivity risk not known.1

Continue to monitor for antibodies in patients with an immune response to other enzyme replacement therapies who are switched to velaglucerase alfa.1

Specific Populations

Category B.1 No adequate and well-controlled studies in pregnant women; use during pregnancy only if clearly needed.1 Animal studies suggest no evidence of fetal harm.1

Not known whether velaglucerase alfa is distributed into milk.1 Use with caution.1 Consider the known benefits of breast-feeding along with the woman's clinical need for velaglucerase alfa and any potential adverse effects of the drug or disease on the infant.1

Safety and efficacy not established in children <4 years of age.1

Clinical response and adverse effects in geriatric patients appear to be similar to those of younger adults; in general, select dosage with caution in geriatric patients.1

Common Adverse Effects

Hypersensitivity reactions, headache, dizziness, pyrexia, abdominal pain, back pain, joint pain, asthenia/fatigue, prolonged aPTT, nausea.1

• If you have an allergy to velaglucerase alfa or any other part of velaglucerase alfa.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take velaglucerase alfa. This includes your doctors, nurses, pharmacists, and dentists.
• Some patients have very bad side effects during the infusion. Tell your doctor if you have any bad effects during the infusion.
• Other drugs may be given before this medicine to help avoid side effects.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using velaglucerase alfa while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

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:

• Headache.
• Dizziness.
• Belly pain.
• Back pain.
• Joint pain.
• Feeling tired or weak.
• Upset stomach.
• Runny nose.
• Stuffy nose.
• Nose and throat irritation.

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.

(vel a GLOO ser ase AL fa)

Gaucher disease: For long-term enzyme replacement therapy for pediatric and adult patients with type 1 Gaucher disease.

No dosage adjustment provided in manufacturer's labeling.

IV: Infuse over 1 hour; use an inline, low protein-binding 0.2 micron filter during infusion. Do not infuse other products in the same infusion tubing.

Store intact vials at 2°C to 8°C (36°F to 46°F). Once reconstituted, the product should be used immediately. If immediate use is not possible, the reconstituted or diluted product may be stored for up to 24 hours at 2°C to 8°C (36°F to 46°F). The infusion should be completed within 24 hours of reconstitution. Do not freeze. Protect from light. Discard any unused solution.

Disease monitoring: CBC, liver enzymes, IgG antibodies; MRI, CT, or US of liver and spleen; bone density studies; monitor antibodies in those patients who developed antibodies to other enzyme replacement therapies

Applies to velaglucerase alfa: intravenous powder for injection

General

The most common side effects were hypersensitivity/infusion-related reactions. The most serious side effects reported were hypersensitivity reactions.[Ref]

Hypersensitivity

The term "hypersensitivity reaction" included any event related to and occurring within up to 24 hours of drug infusion, including at least 1 case of anaphylaxis.

The most common symptoms of hypersensitivity reactions were headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia; reactions were generally mild. In therapy-naive patients, onset was usually during the first 6 months of therapy and occurred less often over time.[Ref]

Very common (10% or more): Hypersensitivity reaction (up to 52%)
Frequency not reported: Anaphylaxis, anaphylactoid reaction[Ref]

Nervous system

Very common (10% or more): Headache (up to 35%), dizziness (up to 22%)
Frequency not reported: Paresthesia[Ref]

Other

Very common (10% or more): Pyrexia/increased body temperature (up to 22%), asthenia/fatigue (13%), infusion-related reaction
Common (1% to 10%): Flushing
Frequency not reported: Peripheral edema, influenza-like illness[Ref]

Gastrointestinal

Very common (10% or more): Abdominal pain (up to 19%)
Common (1% to 10%): Nausea, upper abdominal pain
Frequency not reported: Diarrhea, vomiting[Ref]

Musculoskeletal

Very common (10% or more): Back pain (up to 18%), knee joint pain (up to 15%), arthralgia, bone pain
Frequency not reported: Muscle spasm, myalgia, neck pain[Ref]

Hematologic

Very common (10% or more): Prolonged activated partial thromboplastin time (up to 11%)[Ref]

Cardiovascular

Common (1% to 10%): Tachycardia, hypertension, hypotension[Ref]

Dermatologic

Common (1% to 10%): Rash, urticaria
Frequency not reported: Allergic dermatitis, tinea versicolor, pruritus[Ref]

Immunologic

Common (1% to 10%): IgG antibodies to velaglucerase alfa, positive for neutralizing antibody[Ref]

Respiratory

Frequency not reported: Influenza, nasopharyngitis, rhinitis, bronchitis, cough, epistaxis

Genitourinary

Frequency not reported: Cystitis, urinary tract infection

Some side effects of velaglucerase alfa may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.