Agammaglobulinemia Medication
- Author: Terry W Chin, MD, PhD; Chief Editor: Harumi Jyonouchi, MD more...
Medication Summary
Replacement therapy with intravenous immunoglobulin in patients with primary immune deficiencies
The overall consensus among clinical immunologists is that a dose of intravenous immunoglobulin (IVIG) of 400-600 mg/kg/mo or a dose that maintains trough serum IgG levels greater than 500 mg/dL is desirable. Patients with X-linked agammaglobulinemia (XLA) with meningoencephalitis require much higher doses (1 g/kg) and perhaps intrathecal therapy. Measurement of preinfusion (trough) serum IgG levels every 3 months until a steady state is achieved and then every 6 months if the patient is stable. It may be helpful in adjusting the dose of IVIG to achieve adequate serum levels. For persons who have a high catabolism of infused IgG, more frequent infusions (eg, every 2-3 wk) of smaller doses may maintain the serum level in the reference range. The rate of elimination of immunoglobulin (Ig)G may be higher during a period of active infection; measuring serum IgG levels and adjusting to higher dosages or shorter intervals may be required.
For replacement therapy for patients with primary immune deficiency, all brands of IVIG are probably equivalent, although differences in viral inactivation processes are observed (eg, solvent detergent vs pasteurization and liquid vs lyophilized). The choice of brands may depend on the hospital or home care formulary and the local availability and cost. The dose, manufacturer, and lot number should be recorded for each infusion in order to review for adverse events or other consequences.
Recording all side effects that occur during the infusion is crucial. Monitoring liver and renal function test results periodically, approximately 3-4 times yearly, is also recommended. The US Food and Drug Administration (FDA) recommends that, for patients at risk for renal failure (eg, those with preexisting renal insufficiency, diabetes, volume depletion, sepsis, paraproteinemia; those older than 65 y; those who use nephrotoxic drugs), recommended doses should not be exceeded and infusion rates and concentrations should be the minimum levels that are practicable.
The initial treatment should be administered under the close supervision of experienced personnel. The risk of adverse reactions in the initial treatment is high, especially in patients with infections and those who form immune complexes. In patients with active infection, infusion rates may need to be slower and the dose halved (ie, 200-300 mg/kg), with the remaining dose given the next day to achieve a full dose. Treatment should not be discontinued. After achieving normal serum IgG levels, adverse reactions are uncommon unless patients have active infections.
With the new generation of IVIG products, adverse effects are much reduced. Adverse effects include tachycardia, chest tightness, back pain, arthralgia, myalgia, hypertension or hypotension, headache, pruritus, rash, and low-grade fever. More serious reactions are dyspnea, nausea, vomiting, circulatory collapse, and loss of consciousness. Patients with more profound immunodeficiency or patients with active infections have more severe reactions.
Anticomplementary activity of IgG aggregates in the IVIG and the formation of immune complexes are thought to be related to the adverse reactions. The formation of oligomeric or polymeric IgG complexes that interact with Fc receptors and trigger the release of inflammatory mediators is another cause. Most adverse reactions are rate related. Slowing the infusion rate or discontinuing therapy until symptoms subside may diminish the reaction. Pretreatment with ibuprofen (5-10 mg/kg every 6-8 h), acetaminophen (15 mg/kg/dose), diphenhydramine (1 mg/kg/dose), and/or hydrocortisone (6 mg/kg/dose, maximum 100 mg) 1 hour before the infusion may prevent adverse reactions. In some patients with a history of severe side effects, analgesics and antihistamines may be repeated.
Acute renal failure is a rare but significant complication of IVIG treatment. Reports suggest that IVIG products using sucrose as a stabilizer may be associated with a greater risk for this renal complication. Acute tubular necrosis, vacuolar degeneration, and osmotic nephrosis are suggestive of osmotic injury to the proximal renal tubules. The infusion rate for sucrose-containing IVIG should not exceed 3 mg sucrose/kg/min. Risk factors for this adverse reaction include preexisting renal insufficiency, diabetes mellitus, dehydration, age older than 65 years, sepsis, paraproteinemia, and concomitant use of nephrotoxic agents. For patients at increased risk, monitoring BUN and creatinine levels before starting the treatment and prior to each infusion is necessary. If renal function deteriorates, the product should be discontinued.
IgE antibodies to IgA have been reported to cause severe transfusion reactions in IgA-deficient patients. True anaphylaxis has been reported in patients with selective IgA deficiency and common variable immunodeficiency (CVID) who developed IgE antibodies to IgA after treatment with Ig. In actual experience, however, this is very rare. In addition, this is not a problem for patients with XLA (Bruton disease) or severe combined immunodeficiency (SCID). Caution should be exercised in patients who are IgA deficient (< 7 mg/dL) and need IVIG because of IgG subclass deficiencies. IVIG preparations with very low concentrations of contaminating IgA are advised.
Subcutaneous immunoglobulin (SCIG) administration is also possible. The recommended dose is 100-200 mg/kg SC every week. The initial weekly SC dose can be calculated by multiplying the previous IVIG dose by 1.37 and then dividing that dose into weekly doses, based on the patient's previous IVIG treatment interval. For example, if IVIG dosage is 200 mg/kg every 3 weeks, multiply 200 mg/kg by 1.37 and then divide by 3 to get a calculated dose of 91 mg/kg SC every week. The calculated SCIG dose provides systemic exposure similar to that of the previous IVIG dose. SCIG dose should be initiated 1 week after the last IVIG dose. For SCIG administration, do not exceed 15 mL (3200 mg) per injection site, and the administration rate is not to exceed 20 mL/h per injection site.
SCIG therapy has been widely used in Europe for a number of years and has been introduced to the United States in 2006 with a FDA-approved product. A cost comparison analysis was made in France between SCIG and IVIG. SCIG was found to be 25% less expensive.
Table 1. Immune Globulin, Intravenous[42, 43, 44, 45] (Open Table in a new window)
| Brand(Manufacturer) | Manufacturing Process | pH | Additives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs].) | Parenteral Form and Final Concentrations | IgA Content (mcg/mL) |
| Carimune NF (ZLB Behring) | Kistler-Nitschmann fractionation; pH 4 incubation, nanofiltration | 6.4-6.8 | 6% solution: 10% sucrose, < 20 mg NaCl/g protein | Lyophilized powder 3%, 6%, 9%, 12% | Trace |
| Flebogamma (Grifols USA) | Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization | 5.1-6 | Sucrose free, contains 5% D-sorbitol | Liquid 5% | < 50 |
| Gammagard Liquid 10% (Baxter Bioscience) | Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation | 4.6-5.1 | 0.25M glycine | Ready-for-use liquid 10% | 37 |
| Gammar-P IV (ZLB Behring) | Cohn-Oncley fraction II/III; ultrafiltration; pasteurization | 6.4-7.2 | 5% solution: 5% sucrose, 3% albumin, 0.5% NaCl | Lyophilized powder 5% | < 20 |
| Gamunex (Talecris Biotherapeutics) | Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation | 4-4.5 | Contains no sugar, contains glycine | Liquid 10% | 46 |
| Gammaplex (Bio Products) | Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation | 4.8-5.1 | Contains sorbitol (40 mg/mL); do not administer if fructose intolerant | Ready-for-use solution 5% | < 10 |
| Iveegam EN (Baxter Bioscience) | Cohn-Oncley fraction II/III; ultrafiltration; pasteurization | 6.4-7.2 | 5% solution: 5% glucose, 0.3% NaCl | Lyophilized powder 5% | < 10 |
| Polygam S/D Gammagard S/D (Baxter Bioscience for the American Red Cross) | Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated | 6.4-7.2 | 5% solution: 0.3% albumin, 2.25% glycine, 2% glucose | Lyophilized powder 5%, 10% | < 1.6 (5% solution) |
| Octagam (Octapharma USA) 9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events | Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization | 5.1-6 | 10% maltose | Liquid 5% | 200 |
| Panglobulin (Swiss Red Cross for the American Red Cross) | Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration | 6.6 | Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl | Lyophilized powder 3%, 6%, 9%, 12% | 720 |
| Privigen (CSL Behring) | pH 4 incubation; octanoic acid fractionation, depth filtration, and virus filtration | 4.6-5 | 10% solution; Preservative-free, sucrose-free, and maltose-free | Ready-to-use solution 10% | < 25 |
Although IVIG has improved the patient's ability to handle infections, aggressive treatment for acute bacterial infections with specific antibiotics continues to be necessary. No difference in efficacy among the brands of IVIG is recognized. One review indicated that IVIG at a mean dose of 0.42 g/kg in 162 treatment years resulted in an infection rate similar to the general pediatric population. All 18 children in that study had normal growth patterns. Thus far, the possibility of other infectious agents, notably hepatitis C virus (HCV), has not been a problem in the newer preparations of IVIG, with the additional viral inactivations steps incorporated into the manufacturing processes.
Table 2. Immune Globulin, Subcutaneous (Open Table in a new window)
| Brand(Manufacturer) | Manufacturing Process | pH | Additives | Parenteral Form and Final Concentrations | IgA Content mcg/mL |
| Vivaglobin (ZLB Behring) | Cold ethanol fractionation, pasteurization | 6.4-7.2 | 2.25% glycine, 0.3% NaCl | Liquid 16% (160 mg/mL) | < 50 mcg/mL |
Antibodies
Class Summary
Prevention of respiratory syncytial virus (RSV) in immunodeficient patients is possible with passive immunization humanized mouse monoclonal IgG.
Palivizumab (Synagis)
A humanized mouse monoclonal IgG preparation specifically directed toward RSV.
Immune Globulin, Subcutaneous
Class Summary
Subcutaneous administration of immune globulin provides an alternative method of administration to intravenous in select patients.
Immune globulin, subcutaneous (Vivaglobin)
IgG antibodies that neutralize a wide variety of bacterial and viral agents. Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade. Peak serum IgG levels are lower and trough IgG levels are higher than those achieved with IVIG. SC administration results in stable steady-state IgG levels when administered weekly. Available as a 160-mg/mL SC injectable.
Conley ME, Famer DM, Dobbs AK, et al. A minimally hypomorphic mutation in Btk resulting in reduced B cell numbers but no clinical disease. Clin Exp Immunol. 2008;152:39-44.
Ferrari S, Lougaris V, Caraffi S, et al. Mutations of the Igbeta gene cause agammaglobulinemia in man. J Exp Med. Sep 3 2007;204(9):2047-51. [Medline].
Litzman J, Brysova V, Gaillyova R, et al. Agammaglobulinaemia in a girl with a mosaic of ring 18 chromosome. J Paediatr Child Health. Feb 1998;34(1):92-4. [Medline].
Ohga S, Nakao F, Narazaki O, et al. Hypogammaglobulinaemia in a patient with ring chromosome 21. Arch Dis Child. Sep 1997;77(3):252-4. [Medline].
Revy P, Busslinger M, Tashiro K, et al. A syndrome involving intrauterine growth retardation, microcephaly, cerebellar hypoplasia, B lymphocyte deficiency, and progressive pancytopenia. Pediatrics. Mar 2000;105(3):E39. [Medline].
Roifman CM. Antibody deficiency, growth retardation, spondyloepiphyseal dysplasia and retinal dystrophy: a novel syndrome. Clin Genet. Feb 1999;55(2):103-9. [Medline].
Stewart DM, Tian LL, Notaranelo LD, Nelson DL. X-linked hypogammaglobulinemia and isolated growth hormone deficiency: an update. Immunol Rev. 2008;40:262-70. [Medline].
al-Attas RA, Rahi AH. Primary antibody deficiency in Arabs: first report from eastern Saudi Arabia. J Clin Immunol. Sep 1998;18(5):368-71. [Medline].
Mila J, Matamoros N, Pons de Ves J, et al. [The Spanish Registry of Primary Immunodeficiencies. REDIP-1998]. Sangre (Barc). Apr 1999;44(2):163-7. [Medline].
Leal RC, Bertelli EC, Soler ZA. Recurrent pneumonia caused by genetic immunodeficiency: a prophylactic and rehabililtative approach. Braz J Infect Dis. 2007;11:307-10. [Medline].
Eley BS, Hughes J, Cooper M, Pienaar S, Beatty DW. Primary immunodeficiency diseases at Red Cross War Memorial Children's Hospital. S Afr Med J. Dec 1997;87(12):1684-8. [Medline].
Baumgart KW, Britton WJ, Kemp A, et al. The spectrum of primary immunodeficiency disorders in Australia. J Allergy Clin Immunol. Sep 1997;100(3):415-23. [Medline].
Lam DS, Lee TL, Chan KW, et al. Primary immunodeficiency in Hong Kong and the use of genetic analysis for diagnosis. Hong Kong Med J. Apr 2005;11(2):90-6. [Medline].
Freeman AF, Holland SM. Persistent bacterial infections and primary immune disorders. Curr Opin Microbiol. 2007;10:70-5. [Medline].
Mamishi S, Shahmahmoudi S, Tabatabaie H, et al. Novel BTK mutation presenting with vaccine-associated paralytic poliomyelitis. Eur J Pediatr. Nov 2008;167(11):1335-8. [Medline]. [Full Text].
Hidalgo S, Garcia Erro M, Cisierna D, Freire MC. Paralytic poliomyelitis caused by a vaccine-derived polio virus in an antibody-deficient Argentinean child. Pediatr Infect Dis J. 2003;22:570-2. [Medline].
Rudge P, Webster AD, Revesz T, et al. Encephalomyelitis in primary hypogammaglobulinaemia. Brain. Feb 1996;119 ( Pt 1):1-15. [Medline].
Katamura K, Hattori H, Kunishima T, et al. Non-progressive viral myelitis in X-linked agammaglobulinemia. Brain Dev. Mar 2002;24(2):109-11. [Medline].
Tasca G, Iorio R, Basile U, et al. Progressive multifocal leukoencephalopathy in a patient with Franklin disease and hypogammaglobulinemia. J Neurol Sci. Sep 15 2009;284(1-2):203-4. [Medline].
Bloom KA, Chung D, Cunningham-Rundles C. Osteoarticular infectious complications in patients with primary immunodeficiencies. Curr Opin Rheumatol. Jul 2008;20(4):480-5. [Medline]. [Full Text].
Bonkowsky JL, Bohnsack JF, Pennington MJ, et al. Leukoencephalopathy, arthritis, colitis, and hypogammaglobulinemia (LACH) in two brothers: a novel syndrome?. Am J Med Genet A. 2004;128:52-6. [Medline].
Akman S, Guven AG, Ince S, et al. IgG and IgG subclasses deficiency in children undergoing continuous ambulatory peritoneal dialysis and its provocative factors. Pediatr Int. Jun 2002;44(3):273-6. [Medline].
Rehman S, Bytnar D, Berkenbosch JW, et al. Hypogammaglobulinemia in pediatric ICU patients. J Intensive Care Med. Sep-Oct 2003;18(5):261-4. [Medline].
Gulino AV. WHIM syndrome: a genetic disorder of leukocyte trafficking. Curr Opin Allergy Clin Immunol. 2003;3:443-50. [Medline].
Lynn J, Knight AK, Kamoun M, Levinson AI. A 55-year-old man with hypogammaglobulinemia, lymphopenia, and unrelenting cutaneous warts. J Allergy Clin Immunol. Aug 2004;114(2):409-14. [Medline].
Agarwal S, Cunningham-Rundles C. Thymoma and immunodeficiency (Good syndrome): a report of 2 unusual cases and review of the literature. Ann Allergy Asthma Immunol. 2007;98:185-90. [Medline].
Onigbanjo MT, Orange JS, Perez EE, Sullivan KE. Hypogammaglobulinemia in a pediatric tertiary care setting. Clin Immunol. 2007;125:52-9. [Medline].
Sawada A, Takihara Y, Kim JY, et al. A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans. J Clin Invest. Dec 2003;112(11):1707-13. [Medline].
Okumura A, Tsuge I, Kamachi Y et al. Transient hypogammaglobulinemia after antileptic drug hypersensitivity. Pediatr Neurol. 2007;36:342-4. [Medline].
Boccara O, Valevrie-Allanore L, Crickx B et al. Association of hypogammaglobulinemia with DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Eur J Dermatol. 2006;16:666-8. [Medline]. [Full Text].
Kawano T, Matsuse H, Obase Y, et al. Hypogammaglobulinemia in steroid-dependent asthmatics correlates with the daily dose of oral prednisolone. Int Arch Allergy Immunol. Jul 2002;128(3):240-3. [Medline].
Kitamura A, Takiguchi Y, Tochigi N, et al. Durable hypogammaglobulinemia associated with thymoma (Good syndrome). Intern Med. 2009;48(19):1749-52. [Medline].
Yong PF, Aslam L, Karim MY, Khamashta MA. Management of hypogammaglobulinaemia occurring in patients with systemic lupus erythematosus. Rheumatology (Oxford). Sep 2008;47(9):1400-5. [Medline].
Carneiro-Sampaio M, Liphaus BL, Jesus AA, Silva CA, Oliveira JB, Kiss MH. Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies. J Clin Immunol. May 2008;28 Suppl 1:S34-41. [Medline].
Orange JS, Geha RS, Bonilla FA. Acute chylothorax in children: selective retention of memory T cells and natural killer cells. J Pediatr. 2003;143:243-9. [Medline].
Bezrodnik L, Raccio AC, Canil LM, Rey MA, Carabajal PC, FOssati CA, et al. Hypogammaglobulinemia secondary to cow-milk allergy in children under 2 years of age. Immunology. 2007;122:140-6. [Medline].
Bondioni MP, Duse M, Plebani A et al. Pulmonary and sinusal changes in 45 patients with primary immunodeficiencies: computed tompgraphy evaluation. J Comput Assist Tompgr. 2007;31:620-8. [Medline].
Rusconi F, Panisi C, Dellepiane RM, et al. Pulmonary and sinus diseases in primary humoral immunodeficiencies with chronic productive cough. Arch Dis Child. Dec 2003;88(12):1101-5. [Medline].
Chinen J, Shearer WT. Subcutaneous immunoglobulins: alternative for the hypogammaglobulinemic patient?. J Allergy Clin Immunol. 2004;114:934-5. [Medline].
Ochs, HD, Gupta S, Kiseeling P et al. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006;26:265-73. [Medline].
Gustafson R, Gardulf A, Hansen S et al. Rapid subcutaneous immunoglobulin administration every second week results in high and stable serum immunoglobulin G levels in patients with primary antibody deficiencies. Clin Exp Immunol. 2008;152:274-9. [Medline].
Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug Information Handbook 2008-2009. 16th edition. Cleveland, OH: Lexi-Comp Inc; 2008.
Hooper JA. Intravenous immunoglobulins: evolution of commercial IVIG preparations. Immunol Allergy Clin North Am. Nov 2008;28(4):765-78, viii. [Medline].
Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health Syst Pharm. Aug 15 2005;62(16 Suppl 3):S5-11. [Medline].
Siegel J. The Product: All intravenous immunoglobulins are not equivalent. Pharmacother. 2005;25(11 Pt 2):78S-84S.
Howard V, Myers LA, Williams DA, et al. Stem cell transplants for patients with X-linked agammaglobulinemia. Clin Immunol. May 2003;107(2):98-102. [Medline].
Quinti I, Pierdominici M, Marziali M, et al. European surveillance of immunoglobulin safety--results of initial survey of 1243 patients with primary immunodeficiencies in 16 countries. Clin Immunol. Sep 2002;104(3):231-6. [Medline].
Buckley RH. Pulmonary complications of primary immunodeficiencies. Paediatr Respir Rev. 2004;5 (Suppl A):S225-33. [Medline].
Patiroglu T, Akyildiz B, Patiroglu TE, Gulmez IY. Recurrent pulmonary alveolar proteinosis secondary to agammaglobulinemia. Pediatr Pulmonol. Jul 2008;43(7):710-3. [Medline].
Berlucchi M, Soresina A, Redaelli De Zinis LO, et al. Sensorineural hearing loss in primary antibody deficiency disorders. J Pediatr. Aug 2008;153(2):293-6. [Medline].
Brosens LA, Tytgat KM, Morsink FH et al. Multiple colorectal neoplasms in X-linked agammaglobulinemia. Clin Gastroenterol Hepatol. 2008;6:115-9. [Medline].
Ziegner UH,, Kobayashi RH, Cunningham-Rundles C, et al. Progressive neurodegeneration in patients with primary immunodeficiency disease on IVIG treatment. Clin Immunol. 2002;102:19-24. [Medline].
Papapetropoulos S, Friedman J, Blackstone C et al. A progressive, fatal dystonia-Parkinsonism syndrome in a patient with primary immunodeficiency receiving chronic IBIG therapy. Mov Disord. 2007;22:1664-6. [Medline].
Dalal I, Reid B, Nisbet-Brown E, Roifman CM. The outcome of patients with hypogammaglobulinemia in infancy and early childhood. J Pediatr. Jul 1998;133(1):144-6. [Medline].
Kidon MI, Handzel ZT, Schwartz R, et al. Symptomatic hypogammaglobulinemia in infancy and childhood - clinical outcome and in vitro immune responses. BMC Fam Pract. Oct 21 2004;5:23. [Medline].
Desar IM, Weemaes CM, van Deuren M et al. Reversible hypogammaglubulinaemia. Neth J Med. 2007;65:381-5. [Medline].
Abe S, Suzuki T, Hori T, Baba A, Shiraishi H. Hypogammaglobulinemia during antipsychotic therapy. Psychiatry Clin Neurosci. Feb 1998;52(1):115-7. [Medline].
Aghamohammadi A, Moin M, Farhoudi A, et al. Efficacy of intravenous immunoglobulin on the prevention of pneumonia in patients with agammaglobulinemia. FEMS Immunol Med Microbiol. Mar 8 2004;40(2):113-8. [Medline].
Asmar BI, Andresen J, Brown WJ. Ureaplasma urealyticum arthritis and bacteremia in agammaglobulinemia. Pediatr Infect Dis J. Jan 1998;17(1):73-6. [Medline].
Black C, Zavod MB, Gosselin BJ. Haemophilus influenzae lymphadenopathy in a patient with agammaglobulinemia: clinical-histologic-microbiologic correlation and review of the literature. Arch PatholLab Med. 2005;129:100-3. [Medline].
Buehring I, Friedrich B, Schaaf J, et al. Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies. Clin Exp Immunol. Sep 1997;109(3):468-72. [Medline].
Conley ME. Early defects in B cell development. Curr Opin Allergy Clin Immunol. 2002;2:517-22. [Medline].
Conley ME, Broides A, Hernandez-Trujillo V, et al. Genetic analysis of patients with defects in early B-cell development. Immunol Rev. 2005;203:216-34. [Medline].
Conley ME, Dobbs AK, Farmer DM, et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol. 2009;27:199-227. [Medline].
Dittrich AM, Schulze I, Magdorf K, et al. X-linked agammaglobulinaemia and Pneumocystis carinii pneumonia--an unusual coincidence?. Eur J Pediatr. Jun 2003;162(6):432-3. [Medline].
Eijkhout HW, van Der Meer JW, Kallenberg CG, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. Aug 7 2001;135(3):165-74. [Medline].
Feydy A, Sibilia J, De Kerviler E, et al. Chest high resolution CT in adults with primary humoral immunodeficiency. Br J Radiol. Dec 1996;69(828):1108-16. [Medline].
Fijolek J, Wiatr E, Demkow U, Orlowsk TM. Immunological disturbances in Good's syndrome. Clin Invest Med. Aug 1 2009;32(4):E301-6. [Medline].
Halsey NA, Pinto J, Espinosa-Rosales F et al. Search for poliovirus carriers among people with primary immune deficiency diseases in the United States, Mexico, Brazil and the United Kingdom. Bull World Heatlh Organ. 2004;82:3-8. [Medline].
Kainulainen L, Nikoskelainen J, Vuorinen T, et al. Viruses and bacteria in bronchial samples from patients with primary hypogammaglobulinemia. Am J Respir Crit Care Med. Apr 1999;159(4 Pt 1):1199-204. [Medline].
Kano Y, Inaoka M, Shiohara T. Association between anticonvulsant hypersensitivity syndrome and human herpes 6 reactivation and hypogammaglobulinemia. Arch Dermatol. 2004;140:183-8. [Medline].
Kawai T, Malech HL. WHIM syndrome: congenital immune deficiency disease. Curr Opin Hematol. Jan 2009;16(1):20-6. [Medline]. [Full Text].
Kutukculer N, Gulez N. The outcome of patients with unclassified hypogammaglobulinemia in early childhood. Pediatr Allergy Immunol. Nov 2009;20(7):693-8. [Medline].
Morales P, Hernandez D, Vicente R, et al. Lung transplantation in patients with x-linked agammaglobulinemia. Transplant Proc. Aug 2003;35(5):1942-3. [Medline].
Mueller BU, Pizzo PA. Cancer in children with primary or secondary immunodeficiencies. J Pediatr. Jan 1995;126(1):1-10. [Medline].
Ozdoba C, Ramelli G, Schroth G. MRI in a patient with congenital agammaglobulinaemia. Neuroradiology. Aug 1998;40(8):516-8. [Medline].
Plebani A, Soresina A, Rondelli R, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin Immunol. Sep 2002;104(3):221-30. [Medline].
Quartier P, Debre M, De Blic J, et al. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr. May 1999;134(5):589-96. [Medline].
Raynaud M, Ronce N, Ayrault AD, et al. X-linked mental retardation with isolated growth hormone deficiency is mapped to Xq22-Xq27.2 in one family. Am J Med Genet. Mar 19 1998;76(3):255-61. [Medline].
Skull S, Kemp A. Treatment of hypogammaglobulinaemia with intravenous immunoglobulin, 1973-93. Arch Dis Child. Jun 1996;74(6):527-30. [Medline].
Teramoto T, Kaneko H, Funato M, et al. Progressive multifocal leukoencephalopathy in a patient with X-linked agammaglobulinemia. Scand J Infect Dis. 2003;35(11-12):909-10. [Medline].
Tokuda K, Nishi J, Miyanohara H, et al. Relapsing cellulitis associated with Campylobacter coli bacteremia in an agammaglobulinemic patient. Pediatr Infect Dis J. Jun 2004;23(6):577-9. [Medline].
Wang LJ, Yang YH, Lin YT, Chiang BL. Immunological and clinical features of pediatric patients with primary hypogammaglobulinemia in Taiwan. Asian Pac J Allergy Immunol. 2004;22:25-31. [Medline].
| Brand(Manufacturer) | Manufacturing Process | pH | Additives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs].) | Parenteral Form and Final Concentrations | IgA Content (mcg/mL) |
| Carimune NF (ZLB Behring) | Kistler-Nitschmann fractionation; pH 4 incubation, nanofiltration | 6.4-6.8 | 6% solution: 10% sucrose, < 20 mg NaCl/g protein | Lyophilized powder 3%, 6%, 9%, 12% | Trace |
| Flebogamma (Grifols USA) | Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization | 5.1-6 | Sucrose free, contains 5% D-sorbitol | Liquid 5% | < 50 |
| Gammagard Liquid 10% (Baxter Bioscience) | Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation | 4.6-5.1 | 0.25M glycine | Ready-for-use liquid 10% | 37 |
| Gammar-P IV (ZLB Behring) | Cohn-Oncley fraction II/III; ultrafiltration; pasteurization | 6.4-7.2 | 5% solution: 5% sucrose, 3% albumin, 0.5% NaCl | Lyophilized powder 5% | < 20 |
| Gamunex (Talecris Biotherapeutics) | Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation | 4-4.5 | Contains no sugar, contains glycine | Liquid 10% | 46 |
| Gammaplex (Bio Products) | Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation | 4.8-5.1 | Contains sorbitol (40 mg/mL); do not administer if fructose intolerant | Ready-for-use solution 5% | < 10 |
| Iveegam EN (Baxter Bioscience) | Cohn-Oncley fraction II/III; ultrafiltration; pasteurization | 6.4-7.2 | 5% solution: 5% glucose, 0.3% NaCl | Lyophilized powder 5% | < 10 |
| Polygam S/D Gammagard S/D (Baxter Bioscience for the American Red Cross) | Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated | 6.4-7.2 | 5% solution: 0.3% albumin, 2.25% glycine, 2% glucose | Lyophilized powder 5%, 10% | < 1.6 (5% solution) |
| Octagam (Octapharma USA) 9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events | Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization | 5.1-6 | 10% maltose | Liquid 5% | 200 |
| Panglobulin (Swiss Red Cross for the American Red Cross) | Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration | 6.6 | Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl | Lyophilized powder 3%, 6%, 9%, 12% | 720 |
| Privigen (CSL Behring) | pH 4 incubation; octanoic acid fractionation, depth filtration, and virus filtration | 4.6-5 | 10% solution; Preservative-free, sucrose-free, and maltose-free | Ready-to-use solution 10% | < 25 |
| Brand(Manufacturer) | Manufacturing Process | pH | Additives | Parenteral Form and Final Concentrations | IgA Content mcg/mL |
| Vivaglobin (ZLB Behring) | Cold ethanol fractionation, pasteurization | 6.4-7.2 | 2.25% glycine, 0.3% NaCl | Liquid 16% (160 mg/mL) | < 50 mcg/mL |
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