Carimune NF (Immune Globulin Intravenous (Human)) - Indications and Dosage

INDICATIONS AND USAGE

IMMUNODEFICIENCY

Immune Globulin Intravenous (Human), Carimune™ NF, is indicated for the maintenance treatment of patients with primary immunodeficiencies (PID), e.g., common variable immunodeficiency, X-linked agammaglobulinemia, severe combined immunodeficiency (15,17,18,19). Carimune™ NF is preferable to intramuscular Immune Globulin (Human) preparations in treating patients who require an immediate and large increase in the intravascular immunoglobulin level (13), in patients with limited muscle mass, and in patients with bleeding tendencies for whom intramuscular injections are contraindicated. The infusions must be repeated at regular intervals. Please see DOSAGE AND ADMINISTRATION section.

IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

Acute

A controlled study was performed in children in which Immune Globulin Intravenous (Human), Carimune™, was compared with steroids for the treatment of acute (defined as less than 6 months duration) ITP. In this study sequential platelet levels of 30,000, 100,000, and 150,000/µL were all achieved faster with Carimune™ than with steroids and without any of the side effects associated with steroids (14,20). However, it should be noted that many cases of acute ITP in childhood resolve spontaneously within weeks to months. Carimune™ has been used with good results in the treatment of acute ITP in adult patients (21,22,23). In a study involving 10 adults with ITP of less than 16 weeks duration, Carimune™ therapy raised the platelet count to the normal range after a 5 day course. This effect lasted a mean of over 173 days, ranging from 30 to 372 days (24).

Chronic

Children and adults with chronic (defined as greater than 6 months duration) ITP have also shown an increase (sometimes temporary) in platelet counts upon administration of Immune Globulin Intravenous (Human), Carimune™, (20,24,25,26,27,28). Therefore, in situations that require a rapid rise in platelet count, for example prior to surgery or to control excessive bleeding, use of Carimune™ should be considered. In children with chronic ITP, Carimune™ therapy resulted in a mean rise in platelet count of 312,000/µL with a duration of increase ranging from 2 to 6 months (25,28). Carimune™ therapy may be considered as a means to defer or avoid splenectomy (27,28,29). In adults, Carimune™ therapy has been shown to be effective in maintaining the platelet count in an acceptable range with or without periodic booster therapy. The mean rise in platelet count was 93,000/µL and the average duration of the increase was 20-24 days (24,25). However, it should be noted that not all patients will respond. Even in those patients who do respond, this treatment should not be considered to be curative.

DOSAGE AND ADMINISTRATION

It is generally advisable not to dilute plasma derivatives with other infusable drugs. Immune Globulin Intravenous (Human), Carimune™ NF, should be given by a separate infusion line. No other medications or fluids should be mixed with Carimune™ NF preparation.

Carimune™ NF should be used with caution in patients with pre-existing renal insufficiency and in patients judged to be at increased risk of developing renal insufficiency (including, but not limited to those with diabetes mellitus, age greater than 65, volume depletion, paraproteinemia, sepsis, and patients receiving known nephrotoxic drugs). In these cases especially it is important to assure that patients are not volume depleted prior to Carimune™ NF infusion. 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, recommended doses should not be exceeded and the concentration and infusion rate selected should be the minimum practicable. The product should be infused at a rate less than 2 mg/kg/min.

ADULT AND CHILD SUBSTITUTION THERAPY

The usual dose of Immune Globulin Intravenous (Human), Carimune™ NF in immunodeficiency syndromes is 0.2 g/kg of body weight administered once a month by intravenous infusion. If the clinical response is inadequate, the dose may be increased to 0.3 g/kg of body weight or the infusion may be repeated more frequently than once a month (15,17,18,19).

The first infusion of Carimune™ NF in previously untreated agammaglobulinemic or hypogammaglobulinemic patients must be given as a 3% immunoglobulin solution (use the total volume of fluid provided, or see Table 3, to reconstitute the lyophilized product).

1. Start with a flow rate of 10-20 drops (0.5-1.0 mL) per minute.
2. After 15-30 minutes the rate of infusion may be further increased to 30-50 drops (1.5-2.5 mL) per minute.
3. After the first bottle of 3% solution is infused and the patient shows good tolerance, subsequent infusions may be administered at a higher rate or concentration. Such increases should be made gradually allowing 15-30 minutes before each increment.

The first infusion of Carimune™ NF in previously untreated agammaglobulinemic and hypogammaglobulinemic patients may lead to systemic side effects. The nature of these effects has not been fully elucidated. Some of them may be due to the release of proinflammatory cytokines by activated macrophages in immunodeficient recipients (56,57). Subsequent administration of Carimune™ NF to immunodeficient patients as well as to normal individuals usually does not cause further untoward side effects.

THERAPY OF IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

INDUCTION

0.4 g/kg of body weight on 2-5 consecutive days.

ACUTE ITP-CHILDHOOD

In acute ITP of childhood, if an initial platelet count response to the first two doses is adequate (30-50,000/µL), therapy may be discontinued after the second day of the 5 day course (20).

MAINTENANCE-CHRONIC ITP

In adults and children, if after induction therapy the platelet count falls to less than 30,000/µL and/or the patient manifests clinically significant bleeding, 0.4 g/kg of body weight may be given as a single infusion. If an adequate response does not result, the dose can be increased to 0.8-1.0 g/kg of body weight given as a single infusion (21,58,59).

RECONSTITUTION

(see also pictures next page)

1. Remove the protective plastic caps from the lyophilisate and diluent bottles and disinfect both rubber stoppers with alcohol. Remove the protective cover from one end of the transfer set and insert the exposed needle through the rubber stopper into the bottle containing the diluent.

2. & 3. Remove the second protective cover from the other end of the transfer set. Grasp both bottles as shown in picture 2, quickly plunge the diluent bottle onto the lyophilisate bottle and bring the bottles into an upright position. Only if this is done quickly and the bottles are immediately brought into an upright position can the vacuum in the lyophilisate bottle be maintained, thus speeding up reconstitution and facilitating the transfer. Allow the diluent to flow into the lyophilisate bottle.

4. Once the appropriate amount of diluent is transferred (see Table 3), lift the diluent bottle off the spike to release the vacuum. This will reduce foaming and facilitate dissolution. Remove the spike.

5. Swirl vigorously but do not shake, otherwise a foam will form which is very slow to subside. The lyophilisate dissolves within a few minutes.

To reconstitute Carimune™ NF from the individual vial package, or when using other diluents or higher concentrations, Table 3 indicates the volume of sterile diluent required. Observing aseptic technique, this volume should be drawn into a sterile hypodermic syringe and needle. The diluent is then injected into the corresponding Carimune™ NF vial size.

If large doses of Carimune™ NF are to be administered, several reconstituted vials of identical concentration and diluent may be pooled in an empty sterile glass or plastic i.v. infusion container using aseptic technique. Carimune™ NF normally dissolves within a few minutes, though in exceptional cases it may take up to 20 minutes.

DO NOT SHAKE! Excessive shaking will cause foaming.

Any undissolved particles should respond to careful rotation of the bottle. Avoid foaming. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Filtering of Carimune™ NF is acceptable but not required. Pore sizes of 15 microns or larger will be less likely to slow infusion, especially with higher Carimune™ NF concentrations. Antibacterial filters (0.2 microns) may be used. When reconstitution of Carimune™ NF occurs outside of sterile laminar air flow conditions, administration must begin promptly with partially used vials discarded. When reconstitution is carried out in a sterile laminar flow hood using aseptic technique, administration may begin within 24 hours provided the solution has been refrigerated during that time. Do not freeze Carimune™ NF solution.

PROCEED WITH INFUSION ONLY IF SOLUTION IS CLEAR AND AT APPROXIMATELY ROOM TEMPERATURE!

HOW SUPPLIED

Immune Globulin Intravenous (Human), Carimune™ NF Nanofiltered is available as a white lyophilized powder in 1, 3, 6 and 12 g size vials. The only diluents which may be used to reconstitute the product are sterile (0.9%) Sodium Chloride Injection USP, 5% Dextrose, or Sterile Water.

Carimune™ NF is available in individual vial packages.

1g Individual vial package (NDC 44206-415-01)

3g Individual vial package (NDC 44206-416-03)

6g Individual vial package (NDC 44206-417-06)

12g Individual vial package (NDC 44206-418-12)

Please see Table 2 for Calculated Carimune™ NF Osmolality (mOsmol/kg).

STORE AND DISPENSE

Immune Globulin Intravenous (Human), Carimune™ NF, should be stored at room temperature not exceeding 30 °C (86 °F). The preparation should not be used after the expiration date printed on the label.