Bivigam

Primary Humoral Immunodeficiency

BIVIGAM is an Immune Globulin Intravenous (Human), 10% Liquid, indicated for the treatment of adults and pediatric patients 2 years of age and older with primary humoral immunodeficiency (PI).

This includes, but is not limited to, the humoral immune defect in common variable immunodeficiency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.

 Preparation and Handling

• BIVIGAM is a clear or slightly opalescent, colorless to pale yellow solution. Inspect BIVIGAM visually for particulate matter and discoloration prior to administration. Do not use if the solution is cloudy or turbid, or contains particulate matter.
• Allow refrigerated product to come to room temperature before use.
• Do not freeze or heat. Do not use any solution that has been frozen or heated.
• DO NOT SHAKE.
• Do not mix BIVIGAM with other IGIV products or other intravenous medications. If large doses of BIVIGAM are to be administered, several vials may be pooled using aseptic technique into sterile infusion bags and infused.
• Do not dilute BIVIGAM.
• BIVIGAM contains no preservatives. BIVIGAM vial is for single use only. Any vial of BIVIGAM that has been entered should be used promptly and any unused portion should be discarded immediately. Do not reuse or save for future use.
• Maintain BIVIGAM at room temperature during administration.
• Do not use after expiration date.

Recommended Dose

As there are significant differences in the half-life of IgG among patients with primary humoral immunodeficiency, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response.

The recommended dose of BIVIGAM for replacement therapy in primary humoral immunodeficiency in adults and children 2 years of age and older, is 300 to 800 mg/kg body weight administered every 3 to 4 weeks. The dosage may be adjusted over time to achieve the desired trough levels and clinical response.

BIVIGAM dose adjustments may be required in patients who fail to maintain trough total IgG concentrations of at least 500 mg/dL with a target of 600 mg/dL. Starting with the second infusion, the dose will be adjusted proportionally, targeting a trough of ≥ 600 mg/dL, based on the previous trough and the associated dose.

Administration

It has been reported that the frequency of adverse drug reactions to IGIV increases with the infusion rate. Initial infusion rates should be slow. If there are no adverse drug reactions, the infusion rate for subsequent infusions can be slowly increased to the maximum rate. For patients experiencing adverse drug reactions, it is advisable to reduce the infusion rate in subsequent infusions.

Table 1: Recommended Infusion Rates for BIVIGAM

Monitor patient vital signs throughout the infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that is comfortable for the patient.

Ensure that patients with pre-existing renal insufficiency are not volume depleted. For patients judged to be at risk for renal dysfunction or thrombotic events, administer BIVIGAM at the minimum infusion rate practicable, and consider discontinuation of administration if renal function deteriorates ( see Boxed Warning, Warnings and Precautions [5.1, 5.3]).

Pregnancy

No human data are available to indicate the presence or absence of drug-associated risk. Animal reproductive studies have not been conducted with BIVIGAM. It is not known whether BIVIGAM can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. BIVIGAM should be given to pregnant women only if clearly needed. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation

No human data are available to indicate the presence or absence of drug-associated risk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BIVIGAM and any potential adverse effects on the breastfed infant from BIVIGAM or from the underlying maternal condition.

Pediatric Use

BIVIGAM was evaluated in 25 pediatric patients (3 children ages 2 to <6, 9 children ages 6 to <12, and 13 adolescents ages 12 to 16 years) with PI. The safety and effectiveness of BIVIGAM for the treatment of PI has been established in pediatric patients 2 years of age and older, based on data from 2 prospective, open-label, single-arm, multi-center studies, supported by evidence from a population PK analysis of adult and pediatric PK data ( see Adverse Reactions [ 6.1], Clinical Pharmacology [ 12.3], and Clinical Studies [ 14.1]). PK, safety and efficacy were similar to those in adults. No specific dose requirements were necessary to achieve the targeted serum IgG levels in the pediatric subjects.

The safety and effectiveness of BIVIGAM has not been established in pediatric patients with PI who are under the age of 2 ( see Clinical Studies [ 14]).

Geriatric Use

BIVIGAM should be used with caution in patients age 65 and over who are judged to be at increased risk of developing renal insufficiency or thrombotic events (see Boxed Warning, Warnings and Precautions [5.1, 5.3]). Do not exceed recommended doses and administer BIVIGAM at the minimum infusion rate practicable.

BIVIGAM was evaluated in 9 patients age 65 and older with PI. This number of geriatric patients is not sufficient to determine whether they respond differently from younger patients ( see Clinical Studies [14]).