Vpriv

Velaglucerase is a man-made form of an enzyme that occurs naturally in the body. It is used as an enzyme replacement in people with Type I Gaucher disease.

Gaucher disease is a genetic condition in which the body lacks the enzyme needed to break down certain fatty materials (lipids). Lipids can build up in the body, causing symptoms such as easy bruising or bleeding, weakness, anemia, bone or joint pain, enlarged liver or spleen, or weakened bones that are easily fractured.

Velaglucerase may improve the condition of the liver, spleen, bones, and blood cells in people with Type I Gaucher disease. However, velaglucerase is not a cure for this condition.

Velaglucerase 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 velaglucerase alfa if you are allergic to it.

This medicine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

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

Velaglucerase alfa is not approved for use by anyone younger than 4 years old.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure of 94 patients with type 1 Gaucher disease who received VPRIV at doses ranging from 15 Units/kg to 60 Units/kg every other week in 5 clinical studies. Fifty-four (54) patients were naïve to enzyme replacement therapy (ERT) and received VPRIV for 9 months and 40 patients switched from imiglucerase to VPRIV treatment and received VPRIV for 12 months [see Clinical Studies]. Patients were between 4 and 71 years old at time of first treatment with VPRIV, and included 46 male and 48 female patients.

The most serious adverse reactions in patients treated with VPRIV were hypersensitivity reactions [see WARNINGS AND PRECAUTIONS].

The most commonly reported adverse reactions (occurring in ≥ 10% of patients) that were considered related to VPRIV are shown in Table 1. The most common adverse reactions were hypersensitivity reactions.

Table 1: Adverse Reactions Observed in ≥ 10% of Adult and Pediatric Patients with Type 1 Gaucher Disease Treated with VPRIV in the Pooled 5 Clinical Studies

Less common adverse reactions affecting more than one patient ( > 2% in the treatment-naïve group and > 3% in patients switched from imiglucerase to VPRIV treatment) were bone pain, tachycardia, rash, urticaria, flushing, hypertension, and hypotension.

The safety profile of VPR IV was similar between pediatric patients (ages 4 to 17 years) and adult patients. Adverse reactions more commonly seen in pediatric patients compared to adult patients include ( > 10% difference): rash, aPTT prolonged, and pyrexia.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. In clinical studies, 1 of 54 enzyme treatment-naïve patients treated with VPRIV developed IgG class antibodies to VPRIV. In this patient, the antibodies were determined to be neutralizing in an in vitro assay. No hypersensitivity reactions were reported for this patient. It is unknown if the presence of IgG antibodies to VPRIV is associated with a higher risk of infusion reactions. Patients with an immune response to other enzyme replacement therapies who are switching to VPRIV should continue to be monitored for antibodies to VPRIV.

Immunogenicity assay results are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to VPRIV with the incidence of antibodies to other products may be misleading.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Vpriv 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 Vpriv.

• Keep this and all medications out of the reach of children.

Velaglucerase alfa is injected into a vein through an IV. A healthcare provider will give you this injection.

Velaglucerase alfa must be given slowly, and the IV infusion can take at least 1 hour to complete.

Velaglucerase alfa is usually given every other week. Follow your doctor's dosing instructions very carefully.

Your doctor may occasionally change your dose to make sure you get the best results.

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

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of velaglucerase alfa injection in children 4 to 17 years of age. However, safety and efficacy have not been established in children younger than 4 years of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of velaglucerase alfa injection in the elderly.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

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.

None.

• Advise patients that Vpriv is a treatment that is given intravenously every other week. The infusion typically takes up to 60 minutes.
• Advise patients that Vpriv may cause hypersensitivity reactions [see Warnings and Precautions (5.1)].

Vpriv is manufactured by:

Shire Human Genetic Therapies, Inc.
300 Shire Way
Lexington, MA 02421

Vpriv is a registered trademark of Shire Human Genetic Therapies, Inc.

PRINCIPAL DISPLAY PANEL - 400 Unit Vial Carton

NDC 54092-701-04

Vpriv®
(velaglucerase alfa
for injection)
400 units/vial

Single use vial.
Discard unused portion.
For intravenous use only.

Shire

Rx Only

VPRIV is injected into a vein through an IV. A healthcare provider will give you this injection.

VPRIV must be given slowly, and the IV infusion can take at least 1 hour to complete.

VPRIV is usually given every other week. Follow your doctor's dosing instructions very carefully.

Your doctor may occasionally change your dose to make sure you get the best results.

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

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Get emergency medical help if you have signs of an allergic reaction to VPRIV: hives; fever; chest discomfort, difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, nauseated, light-headed, itchy, sweaty, or have fast heartbeats, chest tightness, or trouble breathing.

Common VPRIV side effects may include:

• headache;

• dizziness, feeling tired;

• nausea, stomach pain;

• joint pain, back pain; or

• fever.

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.

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 (the active ingredient contained in VPRIV) 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 VPRIV may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.