Carimune

Generic Name: immune globulin intravenous (human) nanofiltered lyophilized preparation (Carimune)
Brand Name: Carimune
Drug Class: Immune Globulins

Reviewed by Medsayfa.com Last updated october 03, 2024

Patient Information about Carimune

Instruct patients to immediately report symptoms of decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath (which may suggest kidney damage) to their physicians.
Instruct patients to immediately report symptoms of thrombosis. These symptoms may include: pain and/or swelling of an arm or leg with warmth over the affected area, discoloration of an arm or leg, unexplained shortness of breath, chest pain or discomfort that worsens on deep breathing, unexplained rapid pulse, numbness or weakness on one side of the body.

Description of Carimune

Carimune® NF, Nanofiltered, Immune Globulin Intravenous (Human), is a sterile, highly purified polyvalent antibody product containing in concentrated form all the IgG antibodies which regularly occur in the donor population.¹⁵ This immunoglobulin preparation is produced by cold alcohol fractionation from the plasma of US donors. Part of the fractionation may be performed by another US-licensed manufacturer. Carimune® NF is made suitable for intravenous use by treatment at acid pH in the presence of trace amounts of pepsin.^16,17 The manufacturing process by which Carimune® NF is prepared from plasma consists of fractionation and purification steps that comprise filtrations in the presence of filter aids. Four of these steps were validated for virus elimination of both enveloped and non-enveloped viruses. Additionally, the manufacturing process was investigated for its capacity to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE), considered as a model for the vCJD and CJD agents.¹⁸ To complement the existing virus elimination / inactivation mechanism in the Carimune® NF manufacturing process, nanofiltration (removing viruses via size-exclusion) was introduced as an additional virus removal step into the manufacturing process.^19,20 Nanofiltration is performed prior to the viral inactivation step (pH 4 in presence of pepsin) in order to reduce the potential viral load before inactivation is performed. Treatment with pepsin at pH 4 rapidly inactivates enveloped viruses.²¹

The Carimune® NF manufacturing process provides a significant virus reduction capacity as shown in in vitro studies. The results, summarized in Table 1, demonstrate virus clearance during Carimune® NF manufacturing using model viruses for lipid enveloped and nonenveloped viruses.

Table 1: Virus Elimination and Inactivation

Virus	HIV	BVDV	PRV	SFV	SV	BEV
Genome	RNA	RNA	DNA	RNA	RNA	RNA
Envelope	Yes	Yes	Yes	Yes	Yes	No
Size (nm)	80-100	40-60	120-200	50-70	50-70	28-30
Fractionation & Depth filtration	15.5	nt	16.0	9.3	12.4	14.1
pH 4 / pepsin	≥ 6.1	≥ 4.4	≥ 5.3	≥ 6.8	nt	nt
Nanofiltration	≥ 4.9	≥ 4.5	≥ 4.4	nt	≥ 7.5	≥ 5.1
Overall reduction	≥ 26	≥ 9	≥ 25	≥ 16	≥ 19	≥ 19
HIV: Human immunodeficiency virus, model for HIV 1 and HIV 2 BVDV: Bovine viral diarrhea virus, model for HCV (Hepatitis C virus) PRV: Pseudorabies virus, model for large, enveloped DNA viruses (e.g., herpes virus) SFV: Semliki Forest virus, model for HCV SV: Sindbis virus, model for HCV BEV: Bovine enterovirus, model for HAV (Hepatitis A virus) nt: not tested

PRV and the two model viruses for HCV, BVDV and SFV, were inactivated within 1/10, and HIV within ½ of the incubation time (pH 4/pepsin treatment) used during production of Carimune® NF.

Several of the individual production steps in the Carimune® NF manufacturing process have been shown to decrease TSE infectivity of an experimental model agent. TSE reduction steps include precipitation (3.5 logs), depth filtrations (7.3 logs), and nanofiltration (4.4 logs). These studies provide reasonable assurance that low levels of CJD/vCJD agent infectivity, if present in the starting material, would be removed.

The preparation contains at least 96% of IgG and after reconstitution with a neutral unbuffered diluent has a pH of 6.6 ± 0.2. Most of the immunoglobulins are monomeric (7 S) IgG; the remainder consists of dimeric IgG and a small amount of polymeric IgG, traces of IgA and IgM and immunoglobulin fragments.²² The distribution of the IgG subclasses corresponds to that of normal serum.^23–26 Final container lyophilized units are prepared so as to contain 3, 6, or 12 g protein with 1.67 g sucrose and less than 20 mg NaCl per gram of protein. The lyophilized preparation contains no preservative and may be reconstituted with sterile water, 5% dextrose or 0.9% saline to a solution with protein concentrations ranging from 3% to 12% (see Table 4). See Table 2 for calculated Carimune® NF osmolality (mOsm/kg) at each protein concentration. The patient’s fluid, electrolyte, caloric requirements and renal function should be considered in selecting an appropriate diluent and concentration.

Table 2: Calculated Carimune® NF Osmolality (mOsm/kg)

Diluent	Concentration
Diluent	3%	6%	9%	12%
0.9% NaCI	498	690	882	1074
5% Dextrose	444	636	828	1020
Sterile Water	192	384	576	768

REFERENCES

1. Dalakas MC: High-dose intravenous immunoglobulin and serum viscosity: risk of precipitating thromboembolic events. Neurology 1994; 44:223–226.

2. Caress JB, Cartwright MS, Donofrio PD, Peacock JE: The clinical features of 16 cases of stroke associated with administration of IVIg. Neurology 2003; 60:1822–1824.

3. Woodruff RK, Grigg AP, Firkin FC, Smith IL: Fatal thrombotic events during treatment of autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. Lancet 1986; 2:217–218.

4. Jordan S, Cunningham-Rundles C, McEwan R: Utility of intravenous immune globulin in kidney transplantation: efficacy, safety, and cost implications. Am J Transplant 2003; 3:653–664.

5. Wolberg AS, Kon RH, Monroe DM, Hoffman M: Coagulation factor XI is a contaminant in intravenous immunoglobulin preparations. Am J Hematol 2000; 65:30–34.

6. Zaidan R, Al Moallem M, Wani BA, Shameena AR, Al Tahan AR, Daif AK, Al Rajeh S: Thrombosis complicating high dose intravenous immunoglobulin: report of three cases and review of the literature. Eur J Neurology 2003; 10:367–372.

7. Okuda D, Flaster M, Frey J, Sivakumar, K: Arterial thrombosis induced by IVIg and its treatment with tPA. Neurology 2003; 60:1825–1826.

8. Dalakas MC, Clark WM: Strokes, thromboembolic events, and IVIg. Rare incidents blemish an excellent safety record. Neurology 2003; 60:1736–1737.

9. Winward DB, Brophy MT: Acute renal failure after administration of intravenous immunoglobulin: Review of the literature and case report. Pharmacotherapy 1995; 15:765–772.

10. Cantú TG, Hoehn-Saric EW, Burgess KM, Racusen L, Scheel P: Acute renal failure associated with immunoglobulin therapy. Am J Kidney Dis 1995; 25:228–234.

11. Cayco AV, Perazella MA, Hayslett JP: Renal insufficiency after intravenous immune globulin therapy: a report of two cases and an analysis of the literature. J Amer Soc Nephrology 1997; 8:1788–1793.

12. Rault R, Piraino B, Johnston JR, Oral A: Pulmonary and renal toxicity of intravenous immunoglobulin. Clin Nephrol 1991, 36:83–86.

13. Michail S, Nakopoulou L, Stravrianopoulos I, Stamatiadis D, Avdikou K, Vaiopoulos G, Stathakis C: Acute renal failure associated with immunoglobulin administration. Nephrol Dial Transplant 1997; 12:1497–99.

14. Ashan N, Wiegand LA, Abendroth CS, Manning EC: Acute renal failure following immunoglobulin therapy. Am J Nephrol 1996; 16:532–6.

15. Gardi A: Quality control in the production of an immunoglobulin for intravenous use. Blut 1984; 48:337–344.

16. Römer J, Morgenthaler JJ, Scherz R, et al: Characterization of various immunoglobulinpreparations for intravenous application. I. Protein composition and antibody content. Vox Sang 1982; 42:62–73.

17. Römer J, Späth PJ, Skvaril F, et al: Characterization of various immunoglobulin preparations for intravenous application. II. Complement activation and binding to Staphylococcus protein A. Vox Sang 1982; 42:74–80.

18. Gregori L, Maring JA, MacAuley C et al: Partitioning of TSE infectivity during ethanol fractionation of human plasma. Biologicals 2004; 32:1–10.

19. Omar A, and Kempf C: Removal of neutralized model Parvoviruses and Enteroviruses in human IgG solutions by nanofiltration. Transfusion 2002; 42:1005–1010.

20. Späth P, Kempf C, and Gold R: Herstellung, Verträglichkeit und Virussicherheit von intravenösem Immunglobulin. In “Immunglobuline in der Neurobiologie” (P. Berlit, ed.), Steinkopff Verlag, Darmstadt, BRD 2001, pp 1–42.

21. Kempf C, Morgenthaler JJ, Rentsch M, and Omar A: Viral safety and manufacturing of an intravenous immunoglobulin. In “Intravenous Immunoglobulin Research and Therapy” Kazatchkine and Morell, eds. Parthenon Publishing Group. 1996, pp 11–18.

22. Römer J, Späth PJ: Molecular composition of immunoglobulin preparations and its relation to complement activation, in Nydegger UE (ed): Immunohemotherapy: A Guide to Immunoglobulin Prophylaxis and Therapy. London, Academic Press 1981, pp 123–130.

23. Skvaril F, Roth-Wicky B, and Barandun S: IgG subclasses in human-g-globulin preparations for intravenous use and their reactivity with Staphylococcus protein A. Vox Sang 1980; 38:147.

24. Skvaril F: Qualitative and quantitative aspects of IgG subclasses in i.v. immunoglobulin preparations, in Nydegger UE (ed): Immunohemotherapy: A Guide to Immunoglobulin Prophylaxis and Therapy. London, Academic Press, 1981, pp 113–122.

25. Skvaril F, and Barandun S: In vitro characterization of immunoglobulins for intravenous use, in Alving BM, Finlayson JS (eds): Immunoglobulins: Characteristics and Uses of Intravenous Preparations, DHHS Publication No. (FDA)-80-9005. US Government Printing Office, 1980, pp 201–206.

26. Burckhardt JJ, Gardi A, Oxelius V, et al: Immunoglobulin G subclass distribution in three human intravenous immunoglobulin preparations. Vox Sang 1989; 57:10–14.

Indications of Carimune

Immunodeficiency

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.^30,32-34 Carimune® NF is preferable to intramuscular Immune Globulin (Human) preparations in treating patients who require an immediate and large increase in the intravascular immunoglobulin level²⁸, 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 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.^29,35 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.^36–38 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.³⁹

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 Carimune®.^35,39-43 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.^40,43

Carimune® therapy may be considered as a means to defer or avoid splenectomy.^42–44In 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.^39,40 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. 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

Table 3: Infusion Rates for Carimune® NF Concentrations

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	0.016/ 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
* Maximum infusion rate for patients at risk of renal dysfunction or thromboembolic events. † For patients not at risk of renal dysfunction of thromboembolic events.

Reconstitution

(see also pictures next page)

1. Remove the protective plastic caps from the lyophilisate (LYO) and diluents 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 a 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.

Table 4: Required Diluent Volume*

Target	3 g	6 g	12 g
Concentration	Vial	Vial	Vial
3%	100 mL	200 mL	†
6%	50 mL	100 mL	200 mL
9%	33 mL	66 mL	132 mL
12%	25 mL	50 mL	100 mL
* In patients judged to be at increased risk of developing renal insufficiency and thromboembolic events, the concentration and infusion rate of Carimune® NF should be the minimum practicable. † Container not large enough to permit this concentration.

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 the Carimune

Carimune® NF is available as a white lyophilized powder in 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.

Each product presentation includes a package insert and the following components:

Presentation	Carton NDC Number	Components
3 g	44206-416-03	Carimune NF in a single-use vial [NDC 44206-416-90] One double-ended transfer spike for reconstitution
6 g	44206-417-06	Carimune NF in a single-use vial [NDC 44206-417-91] One double-ended transfer spike for reconstitution
12 g	44206-418-12	Carimune NF in a single-use vial [NDC 44206-418-92] One double-ended transfer spike for reconstitution

Storage And Handling

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.

REFERENCES

28. Morell A, Schürch B, Ryser D, et al: In vivo behaviour of gamma globulin preparations. Vox Sang 1980; 38:272.

29. Imbach P, Barandun S, d’Apuzzo V, et al: High-dose intravenous gamma globulin for idiopathic thrombocytopenic purpura in childhood. Lancet 1981; 1:1228.

30. Barandun S, Morell A, Skvaril F: Clinical experiences with immunoglobulin for intravenous use, in Alving BM, Finlayson JS (eds): Immunoglobulins: Characteristics and Uses of Intravenous Preparations. DHHS Publication No. (FDA)-80-9005. US Government Printing Office, 1980, pp 31–35.

32. Joller PW, Barandun S, Hitzig WH: Neue Möglichkeiten der Immunglobulin- Ersatztherapie bei Antikörpermangel-Syndrom. Schweiz Med Wochenschr 1980; 110:1451.

33. Barandun S, Imbach P, Morell A, et al: Clinical indications for immunoglobulin infusion, in Nydegger UE (ed): Immunohemotherapy: A Guide to Immunoglobulin Prophylaxis and Therapy. London, Academic Press, 1981, pp 275–282.

34. Cunningham-Rundles C, Smithwick EM, Siegal FP, et al: Treatment of primary humoral immunodeficiency disease with intravenous (pH 4.0 treated) gamma globulin, in Nydegger UE (ed): Guide to Immunoglobulin Prophylaxis and Therapy. London, Academic Press, 1981, pp 283–290.

35. Imbach P, Wagner HP, Berchtold W, et al: Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood. Lancet 1985; 2:464.

36. Fehr J, Hofmann V, Kappeler U: Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gamma globulin. N Engl J Med 1982; 306:1254.

37. Müller-Eckhardt C, Küenzlen E, Thilo-Körner D, et al: High-dose intravenous immunoglobulin for posttransfusion purpura. N Engl J Med 1983; 308:287.

38. Wenske G, Gaedicke G, Küenzlen E, et al: Treatment of idiopathic thrombocytopenic purpura in pregnancy by high-dose intravenous immunoglobulin. Blut 1983; 46:347–353.

39. Newland AC, Treleaven JG, Minchinton B, et al: High-dose intravenous IgG in adults with autoimmune thrombocytopenia. Lancet 1983; 1:84–87.

40. Bussel JB, Kimberly RP, Inman RD, et al: Intravenous gammaglobulin for chronic idiopathic thrombocytopenic purpura. Blood 1983; 62:480–486.

41. Abe T, Matsuda J, Kawasugi K, et al: Clinical effect of intravenous immunoglobulin in chronic idiopathic thrombocytopenic purpura. Blut 1983; 47:69–75.

42. Bussel JB, Schulman I, Hilgartner MW, et al: Intravenous use of gamma globulin in the treatment of chronic immune thrombocytopenic purpura as a means to defer splenectomy. J Pediatr 1983; 103:651–654.

43. Imholz B, et al: Intravenous immunoglobulin (i.v. IgG) for previously treated acute or for chronic idiopathic thrombocytopenic purpura (ITP) in childhood: A prospective multicenter study. Blut 1988; 56:63–68.

44. Lusher JM, and Warrier I: Use of intravenous gamma globulin in children with idiopathic thrombocytopenic purpura and other immune thrombocytopenias. Am J Med 1987; 83 (suppl 4A):10–16.

69. Bussel JB, Pham LC, Hilgartner MW, et al: Long-term maintenance of adults with ITP using intravenous gamma globulin. Abstract, American Society of Hematology. New Orleans, December, 1985.

70. Imbach PA, Kühne T, Holländer G: Immunologic aspects in the pathogenesis and treatment of immune thrombocytopenic purpura in children. Current opinion in Pediatrics 1997; 9:35–40.

Manufactured by: CSL Behring AG, Bern, Switzerland. Distributed by: CSL Behring LLC, Kankakee, IL 60901 USA. Revised: September 2013

Side Effects

Increases in creatinine and blood urea nitrogen (BUN) have been observed as soon as one to two days following infusion. Progression to oliguria or anuria, requiring dialysis has been observed. Types of severe renal adverse events that have been seen following IGIV therapy include: acute renal failure, acute tubular necrosis, proximal tubular nephropathy and osmotic nephrosis.^{9-14,64,71–73}

Inflammatory adverse reactions have been described in agammaglobulinemic and hypogammaglobulinemic patients who have never received immunoglobulin substitution therapy before or in patients whose time from last treatment is greater than 8 weeks and whose initial infusion rate exceeds 2 mg/kg/min.

This occurs in approximately 10% of such cases. Such reactions may also be observed in some patients during chronic substitution therapy.

Reactions, which may become apparent only 30 minutes to 1 hour after the beginning of the infusion, are as follows: flushing of the face, feelings of tightness in the chest, chills, fever, dizziness, nausea, diaphoresis, and hypotension or hypertension. In such cases, the infusion should be slowed or temporarily stopped until the symptoms subside. The infusion may then be resumed at a lower rate that is comfortable for the patient. If anaphylaxis or other severe reactions occur, the infusion should be stopped immediately.

Arthralgia, myalgia, and transient skin reactions (such as rash, erythema, pruritus, urticaria, eczema or dermatitis) have also been reported.

Immediate anaphylactoid and hypersensitivity reactions due to previous sensitization of the recipient to certain antigens, most commonly IgA, may be observed in exceptional cases, described under CONTRAINDICATIONS.^30,31,65 In patients with ITP, who receive higher doses (0.4 g/kg/day or greater), 2.9% of infusions may result in adverse reactions.²¹ Headache, generally mild, is the most common symptom noted, occurring during or following 2% of infusions. A few cases of usually mild hemolysis have been reported after infusion of intravenous immunoglobulin products.^59–61 These were attributed to transferal of blood group (e.g., anti-D) antibodies.

Postmarketing

The following adverse reactions have been identified and reported during the post-approval use of IGIV products:

Respiratory

Apnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion-Related Acute Lung Injury (TRALI), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm

Cardiovascular

Cardiac arrest, thromboembolism, vascular collapse, hypotension

Neurological

Coma, loss of consciousness, seizures, tremor

Integumentary

Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis

Hematologic

Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs) test

General/Body as a Whole

Pyrexia, rigors

Musculoskeletal

Back pain

Gastrointestinal

Hepatic dysfunction, abdominal pain

Because postmarketing reporting of these reactions is voluntary and the at-risk populations are of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to exposure to the product. Such is also the case with literature reports authored independently.⁶⁶

Drug Interactions

No information provided.