Drug Detail:Carimune (igiv) (Immune globulin (igiv) (intravenous) [ im-myoon-glob-yoo-lin ])
Generic Name: HUMAN IMMUNOGLOBULIN G 6g
Dosage Form: injection, powder, lyophilized, for solution
Drug Class: Immune globulins
It is generally advisable not to dilute plasma derivatives with other infusable drugs. 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. For patients judged to be at risk for developing renal dysfunction, Carimune® NF should be infused at a rate less than 2 mg/kg/min.
For patients judged to be at an increased risk for thrombosis, a maximum infusion rate of less than 2 mg/kg/min for patients is recommended (see PRECAUTIONS: Thrombosis).
If side effects occur, the infusion should be stopped or slowed until the symptoms subside.
Adult and Child Substitution Therapy
The recommended dose of Carimune® NF in primary immunodeficiency is 0.4 to 0.8 g/kg of body weight administered once every three to four weeks by intravenous infusion.
The first infusion of Carimune® NF in previously untreated agammaglobulinemic or hypogammaglobulinemic patients must be given as a 3% immunoglobulin solution (see Reconstitution). Subsequent infusions may be administered at a higher concentration if the patient shows good tolerance.
An initial infusion rate of 0.5 mg/kg/min is recommended. If tolerated, after 30 minutes, the rate may be increased to 1 mg/kg/min for the next 30 minutes. Thereafter, the rate may be gradually increased in a stepwise manner up to a maximum of 3 mg/kg/min as tolerated. Refer to Table 3 for the corresponding infusion rates in mg/kg/min or mL/kg/min for all product concentrations.
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.67,68 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
The recommended dose of Carimune® NF for the treatment of ITP is 0.4 g/kg of body weight on 2–5 consecutive days. An immunoglobulin solution of 6% (see Reconstitution) is recommended for use in ITP.
The recommended initial infusion rate for the treatment of ITP is 0.5 mg/kg/min. If tolerated, after 30 minutes, the rate may be increased to 1 mg/kg/min for the next 30 minutes. Thereafter, the rate may be gradually increased in a stepwise manner up to a maximum of 3 mg/kg/min as tolerated. Refer to Table 3 for the corresponding infusion rates in mg/kg/min or mL/kg/min for all product concentrations.
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.35
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 g/kg of body weight given as a single infusion.36,69,70
| Concentration (%) |
Initial Infusion Rate: 0.5 mg/kg/min |
1 mg/kg/min | 2 mg/kg/min* | Maximum Infusion Rate†: 3 mg/kg/min |
|---|---|---|---|---|
|
||||
| 3% | 0.0167 mL/kg/min | 0.033 mL/kg/min | 0.067 mL/kg/min | 0.10 mL/kg/min |
| 6% | 0.008 mL/kg/min | 0.0167 mL/kg/min | 0.033 mL/kg/min | 0.050 mL/kg/min |
| 9% | 0.006 mL/kg/min | 0.011 mL/kg/min | 0.022 mL/kg/min | 0.033 mL/kg/min |
| 12% | 0.004 mL/kg/min | 0.008 mL/kg/min | 0.016 mL/kg/min | 0.025 mL/kg/min |
Reconstitution
(see also pictures next page)
| 1. | Remove the protective plastic caps from the lyophilisate (LYO) 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 (picture 1). |
| 2a. and 2b. | Remove the second protective cover from the other end of the transfer set. Grasp both bottles as shown in picture 2a, 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 (picture 2b). |
| 3. | Once the appropriate amount of diluent is transferred (see Table 4), lift the diluent bottle off the spike to release the vacuum (picture 3). This will reduce foaming and facilitate dissolution. Remove the spike. |
| 4. | Swirl vigorously but do not shake, otherwise foam will form which is very slow to subside (picture 4). 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 4 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.
| Target Concentration | 6 g Vial | 12 g Vial | |
|---|---|---|---|
|
|||
| 3% | 200 mL | † | |
| 6% | 100 mL | 200 mL | |
| 9% | 66 mL | 132 mL | |
| 12% | 50 mL | 100 mL | |
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.
