Gammagard S / D (Immune Globulin Intravenous) - Indications and Dosage

INDICATIONS AND USAGE

GAMMAGARD S/D is not indicated in patients with selective IgA deficiency where the IgA deficiency is the only abnormality of concern (see WARNINGS section).

PRIMARY IMMUNODEFICIENCY DISEASES

GAMMAGARD S/D is indicated for the treatment of primary immunodeficient states, such as: congenital agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined immuno-deficiencies. ^6,7 This indication was supported by a clinical trial of 17 patients with primary immunodeficiency who received a total of 341 infusions. GAMMAGARD S/D is especially useful when high levels or rapid elevation of circulating IgG are desired or when intramuscular injections are contraindicated (e.g., small muscle mass).

B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

GAMMAGARD S/D is indicated for prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell Chronic Lymphocytic Leukemia (CLL). In a study of 81 patients, 41 of whom were treated with GAMMAGARD, Immune Globulin Intravenous (Human), bacterial infections were significantly reduced in the treatment group.^8,9 In this study, the placebo group had approximately twice as many bacterial infections as the IGIV group. The median time to first bacterial infection for the IGIV group was greater than 365 days. By contrast, the time to first bacterial infection in the placebo group was 192 days. The number of viral and fungal infections, which were for the most part minor, was not statistically different between the two groups.

IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

When a rapid rise in platelet count is needed to prevent and/or to control bleeding in a patient with Idiopathic Thrombocytopenic Purpura, the administration of GAMMAGARD S/D, should be considered.

The efficacy of GAMMAGARD has been demonstrated in a clinical study involving 16 patients. Of these 16 patients, 13 had chronic ITP (11 adults, 2 children), and 3 patients had acute ITP (one adult, 2 children). All 16 patients (100%) demonstrated a clinically significant rise in platelet count to a level greater than 40,000/mm³ following the administration of GAMMAGARD. Ten of the 16 patients (62.5%) exhibited a significant rise to greater than 80,000 platelets/mm³. Of these 10 patients, 7 had chronic ITP (5 adults, 2 children), and 3 patients had acute ITP (one adult, 2 children).

The rise in platelet count to greater than 40,000/mm³ occurred after a single 1 g/kg infusion of GAMMAGARD in 8 patients with chronic ITP (6 adults, 2 children), and in 2 patients with acute ITP (one adult, one child). A similar response was observed after two 1 g/kg infusions in 3 adult patients with chronic ITP, and one child with acute ITP. The remaining 2 adult patients with chronic ITP received more than two 1 g/kg infusions before achieving a platelet count greater than 40,000/mm³. The rise in platelet count was generally rapid, occurring within 5 days. However, this rise was transient and not considered curative. Platelet count rises lasted 2 to 3 weeks, with a range of 12 days to 6 months. It should be noted that childhood ITP may resolve spontaneously without treatment.

KAWASAKI SYNDROME

GAMMAGARD S/D, is indicated for the prevention of coronary artery aneurysms associated with Kawasaki syndrome. The percentage incidence of coronary artery aneurysm in patients with Kawasaki syndrome receiving GAMMAGARD either at a single dose of 1 g/kg (n=22) or at a dose of 400 mg/kg for four consecutive days (n=22), beginning within seven days of onset of fever, was 3/44 (6.8%). This was significantly different (p=0.008) from a comparable group of patients that received aspirin only in previous trials and of whom 42/185 (22.7%) experienced coronary artery aneurysms. ^10,11,12 All patients in the GAMMAGARD trial received concomitant aspirin therapy and none experienced hypersensitivity-type reactions (urticaria, bronchospasm or generalized anaphylaxis).¹³

Several studies have documented the efficacy of intravenous gammaglobulin in reducing the incidence of coronary artery abnormalities resulting from Kawasaki syndrome.^{10-12, 14-17}

DOSAGE AND ADMINISTRATION

PRIMARY IMMUNODEFICIENCY DISEASES

For patients with primary immunodeficiencies, monthly doses of at least 100 mg/kg are recommended. Initially, patients may receive 200-400 mg/kg. As there are significant differences in the half-life of IgG among patients with primary immunodeficiencies, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response. The minimum serum concentration of IgG necessary for protection has not been established.

B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

For patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell Chronic Lymphocytic Leukemia, a dose of 400 mg/kg every 3 to 4 weeks is recommended.

KAWASAKI SYNDROME

For patients with Kawasaki syndrome, either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses) is recommended.

IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

For patients with acute or chronic Idiopathic Thrombocytopenic Purpura, a dose of 1 g/kg is recommended. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.

No prospective data are presently available to identify a maximum safe dose, concentration, and rate of infusion in patients determined to be at increased risk of acute renal failure. In the absence of prospective data, the recommended doses should not be exceeded and the concentration and infusion rate selected should be the minimum level practicable. Reduction in dose, concentration, and/or rate of administration in patients at risk of acute renal failure has been proposed in the literature in order to reduce the risk of acute renal failure.³²

RECONSTITUTION: USE ASEPTIC TECHNIQUE

When reconstitution is performed aseptically outside of a sterile laminar air flow hood, administration should begin as soon as possible, but not more than 2 hours after reconstitution.

When reconstitution is performed aseptically in a sterile laminar air flow hood, the reconstituted product may be either maintained in the original glass container or pooled into VIAFLEX bags and stored under constant refrigeration (2-8°C), for up to 24 hours. (The date and time of reconstitution/pooling should be recorded). If these conditions are not met, sterility of the reconstituted product cannot be maintained. Partially used vials should be discarded.

1. 5% Solution
   
   1. Note: Reconstitute immediately before use.
   2. If refrigerated, warm the Sterile Water for Injection, USP (diluent) and GAMMAGARD S/D, Immune Globulin Intravenous (Human) (dried concentrate), to room temperature.
   3. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers.
   4. Cleanse stoppers with germicidal solution.
   5. Remove protective covering from the spike at one end of the transfer device (Fig. 1)
      
   6. Place the diluent bottle on a flat surface and, while holding the bottle to prevent slipping, insert the spike of the transfer device perpendicularly through the center of the bottle stopper.
   7. Press down firmly so that the transfer device fits snugly against the diluent bottle (Fig. 2). Caution: Failure to use center of stopper may result in dislodging the stopper.
      
   8. Remove the protective covering from the other end of the transfer device. Hold diluent bottle to prevent slipping.
   9. Hold concentrate bottle firmly and at an angle of approximately 45 degrees. Invert the diluent bottle with the transfer device at an angle complementary to the concentrate bottle (approximately 45 degrees) and firmly insert the transfer device into the concentrate bottle through the center of the rubber stopper (Fig. 3).
      
      Note: Invert the diluent bottle with attached transfer device rapidly into the concentrate bottle in order to avoid loss of diluent.
      Caution: Failure to use center of stopper may result in dislodging the stopper and loss of vacuum.
   10. The diluent will flow into the concentrate bottle quickly. When diluent transfer is complete, remove empty diluent bottle and transfer device from concentrate bottle. Discard transfer device after single use.
   11. Thoroughly wet the dried material by tilting or inverting and gently rotating the bottle (Fig. 4). Do not shake. Avoid foaming.
       
   12. Repeat gentle rotation as long as undissolved product is observed.
2. 10% Solution
   Follow steps 1-4 as previously described in A.
   5.To prepare a 10% solution, reconstitute with the appropriate volume of diluent as indicated in Table 2, which indicates the volume of diluent required for a 5% or 10% concentration. Using aseptic technique, draw the required volume of diluent into a sterile hypodermic syringe and needle. Discard the filled syringe.
   6. Using the residual diluent in the diluent vial, follow steps 5-12 as previously described in A.

RATE OF ADMINISTRATION

It is recommended that initially a 5% solution be infused at a rate of 0.5 mL/kg/Hr. If infusion at this rate and concentration causes the patient no distress, the administration rate may be gradually increased to a maximum rate of 4 mL/kg/Hr. Patients who tolerate the 5% concentration at 4 mL/kg/Hr can be infused with the 10% concentration starting at 0.5 mL/kg/Hr. If no adverse effects occur, the rate can be increased gradually up to a maximum of 8 mL/kg/Hr. For patients judged to be at risk for developing renal dysfunction, it may be prudent to reduce the amount of product infused per unit time by infusing GAMMAGARD S/D, at a rate less than 4 mL/kg/Hr (<3.3 mg IG/kg/min) for a 5% solution or at a rate less than 2 mL/kg/Hr (< 3.3 mg IG/kg/min) for a 10 % solution.

It is recommended that antecubital veins be used especially for 10% solutions, if possible. This may reduce the likelihood of the patient experiencing discomfort at the infusion site (see ADVERSE REACTIONS).

A rate of administration which is too rapid may cause flushing and changes in pulse rate and blood pressure. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.

DRUG INTERACTIONS

Admixtures of GAMMAGARD S/D, Immune Globulin Intravenous (Human), with other drugs and intravenous solutions have not been evaluated. It is recommended that GAMMAGARD S/D be administered separately from other drugs or medications which the patient may be receiving. The product should not be mixed with Immune Globulin Intravenous (Human) from other manufacturers.

Antibodies in immune globulin preparations may interfere with patient responses to live vaccines, such as those for measles, mumps, and rubella. The immunizing physician should be informed of recent therapy with Immune Globulin Intravenous (Human) so that appropriate precautions can be taken.

ADMINISTRATION

GAMMAGARD S/D should be administered as soon after reconstitution as possible, or as described in the DOSAGE AND ADMINISTRATION section.

The reconstituted material should be at room temperature during administration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Reconstituted material should be a clear to slightly opalescent and colorless to pale yellow solution. Do not use if particulate matter and/or discoloration is observed.

Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter.

HOW SUPPLIED

GAMMAGARD S/D is supplied in 2.5 g, 5 g, or 10 g single use bottles. Each bottle of GAMMAGARD S/D is furnished with a suitable volume of Sterile Water for Injection, USP, a transfer device and an administration set which contains an integral airway and a 15 micron filter.

STORAGE

GAMMAGARD S/D is to be stored at a temperature not to exceed 25°C (77°F). Freezing should be avoided to prevent the diluent bottle from breaking.