What data are available to direct dosing of intravenous immunoglobulin G based
on total versus ideal or adjusted body weight?
Intravenous immunoglobulin (IVIG) is a serum antibody preparation of human immunoglobulin
G (IgG) manufactured from pooled human plasma.1 IVIG is Food and Drug
Administration (FDA)-approved for the treatment of various primary immunodeficiency
syndromes and is also utilized in numerous off-label immune-related conditions.2
Although the dosing of IVIG varies by indication, the administered dose is usually
weight-based. Despite the frequent use of weight-based dosing, little data exist
to clarify a safe and efficacious dosing weight for IVIG in overweight or obese
patients. 3 This lack of data is relevant to pharmacy departments, as
unwarranted supratherapeutic dosing may compromise supplies of this costly resource.
This article aims to review clinical and pharmacokinetic data, guideline recommendations,
practice patterns, and practical considerations relevant to weight-based dosing
Body weight is one of the determinants of appropriate IVIG dosing, along with trough
serum levels of immunoglobulin G (IgG) and clinical response. 1 Therefore,
it is important to consider pharmacokinetic parameters when dosing IVIG. The low
volume of distribution (Vd) of IVIG indicates that it minimally distributes
into fat.3,4 Therefore, an overweight or obese patient may not necessarily
experience subtherapeutic outcomes when IVIG is dosed based on ideal body weight
(IBW) or adjusted body weight (ABW). Despite the potential for dosing weight to
influence safety and efficacy of IVIG treatment, few investigations have evaluated
this factor. The ideal trial evaluating clinical efficacy and safety of different
weight-based dosing regimens of IVIG has not been performed. However, some data
demonstrate that body weight and body mass index (BMI) do not influence the IVIG
dose required to produce a target trough IgG level.4
Khan and colleagues evaluated immunoglobulin therapy in 107 patients with common
variable immunodeficiency to evaluate the correlation between IVIG dose and trough
levels of IgG when adjusted for patient weight or BMI.4 All patients
were on a clinician-determined IVIG replacement dose that was stable for at least
6 months. Patients had mean ± standard deviation (SD) weight of 70.8 ± 14.6 kg and
received a mean ± SD annual dose of 383 ± 118 mg/kg every 3 weeks. The analysis
found that trough IgG levels were not correlated with the dose of IVIG when adjusted
for patient weight (R2=0.06, p=0.1) or BMI (R2=0.04, p=0.1),
indicating that dosing based on IBW or ABW may still yield appropriate trough levels
of IgG in patients who receive IVIG.
Guidelines and Expert Opinion
Currently, guidelines in the United States for labeled and unlabeled uses of IVIG
do not provide recommendations on the most appropriate weight to use when calculating
IVIG doses.5-9 However, international guidelines and institutional protocols
provide guidance in this area.10-16
Guidelines from the United Kingdom on the use of IVIG recommended dosing of IVIG
based on ABW in 2007.11 While these 2007 guidelines supported adjusted
doses, this recommendation was removed from the 2008 second edition and the 2011
update, citing the limited evidence to support a firm recommendation.12-13
However, 2008 and 2011 guidelines still provide the formula for dosing based on
ABW, stating there is evidence to support this approach. Also, guidelines published
in Australia and various Canadian provinces recommend adjustment of IVIG dosing
based on ABW.14-16
Citing the pharmacokinetic properties of IVIG presented earlier, Siegel at Ohio
State University Medical Center recommends patients with a BMI of 30 kg/m 2
or higher or who weigh greater than 120% of IBW should be dosed based on ABW.10
The ABW is calculated by adding IBW and 40% of the difference between actual and
IBW. Similarly, the Hospital Corporation of America (HCA) created a policy requiring
all IVIG doses to be based on IBW (except in neonates), rather than total body weight.17
Besides choosing the most appropriate dosing weight, additional steps in dosing
IVIG include rounding the dose to be administered in order to avoid product waste.10
For example, doses can be rounded to the nearest whole vial size to avoid discarding
product from partially used vials. This practice is included in the HCA IVIG policy.17
A recent comprehensive study of global markets found that the use of IVIG is rapidly
growing.18 From 1984 to 2008, the use of IVIG increased by 12% per year,
with the United States and Canada being the leading consumers. Furthermore, usage
can reasonably be expected to increase based on the rise in obesity, the potential
expansion of labeled indications, and continuing widespread use in off-label indications.18-20
Despite the likely rise in demand, the manufacture of IVIG is dependent on supply
of human plasma and whole blood; thus, supplies are ultimately limited.1
Institutions have published results of attempts to address such limited supplies.21,22
A pilot study in Australia reported a 3-year cost savings of at least $781,830 and
reduced consumption of IVIG by 2.4% to 4.2% after instituting a protocol for dosing
IVIG on ABW.21 As such, dosing considerations for IVIG may become increasingly
relevant to maximize product stewardship and cost-effectiveness.
There is a paucity of data evaluating the effect of weight-based dosing of IVIG
on clinical outcomes, and no data clearly indicate whether actual, ideal, or adjusted
body weight is optimal. However, pharmacokinetic studies suggest that dosing based
on ABW may be appropriate and this practice is advocated by various international
guidelines and required by some institutional policies. As consumption of IVIG continues
to increase despite limited supply, stewardship measures including dosing based
on ABW or IBW may promote product conservation and cost-effective drug use.
1. Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health Syst
Pharm. 2005;62(16 Suppl 3):S5-S11.
2. Micromedex Healthcare Series [database online]. Greenwood Village, CO: Thomson
Reuters (Healthcare), Inc; 2013. http://www.thomsonhc.com/hcs/librarian. Accessed
October 19, 2013.
3. Koleba T, Ensom MH. Pharmacokinetics of intravenous immunoglobulin: a systematic
review. Pharmacotherapy. 2006;26(6):813-27.
4. Khan S, Grimbacher B, Boecking C, et al. Serum trough IgG level and annual intravenous
immunoglobulin dose are not related to body size in patients on regular replacement
therapy. Drug Metabolism Letters. 2011;5(2):132-6.
5. Orange JS, Hossny EM, Weiler CR. Use of intravenous immunoglobulin in human disease:
a review of evidence by members of the Primary Immunodeficiency Committee of the
American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol.
6. Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for the diagnosis
and management of primary immunodeficiency. Ann Allergy Asthma Immuno.
2005;94(5 Suppl 1):S1-63.
7. Neunert C, Lim W, Crowther M. The American Society of Hematology 2011 evidence
based practice guideline for immune thrombocytopenia. Blood. 2011 21;117(16):4190-4207.
8. Newburger JW, Takahashi M, Gerber MA. Diagnosis, treatment and long-term management
of Kawasaki disease: a statement for health professionals from the Committee on
Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease
in Young, American Heart Association. Pediatrics. 2004;114(6):1708-1733.
9. Patwas HS, Chaudhry V, Katzberg H, Rae-Grant AD, So YT. Evidence-based guideline:
intravenous immunoglobulin in the treatment of neuromuscular disorders: report of
the Therapeutics and Technology Assessment Subcommittee of the American Academy
of Neurology. Neurology. 2012 ;78(13):1009-1015.
10. Siegel J. Immunoglobulins and obesity. Pharmacy Practice News.
. Accessed September 30, 2013.
11. Wimperis J, Lunn M, Jones A, et al. Clinical guidelines for immunoglobulin use:
second edition update. National Health Services website.
http://www.ivig.nhs.uk/clinicinfo.html. Updated July 2011. Updated January
2010. Accessed September 30, 2013.
12. Provan D, Nokes TJC, Agrawal S, Winer JB, Wood P. Clinical guidelines for the
use of intravenous immunoglobulin. National Health Services website.
http://www.ivig.nhs.uk/clinicinfo.html. Updated 2007. Accessed September 30,
13. Provan D, Nokes TJC, Agrawal S, Winer JB, Wood P. Clinical guidelines for immunoglobulin
use. National Health Services website.
http://www.ivig.nhs.uk/clinicinfo.html. Updated May 2008. Accessed September
14. Criteria for clinical use of intravenous immunoglobulin in Australia. National
Blood Authority Australia website.
http://www.blood.gov.au/ivig-criteria. Updated July 2012. Accessed September
15. Utilization of intravenous immunoglobulin. Newfoundland Labrador Department
of Health and Community Resources website.
http://www.health.gov.nl.ca/health/index.html. Accessed September 30, 2013.
16. Intravenous immunoglobulin. British Columbia Provincial Blood Coordinating Office
. Updated August 2012. Accessed September 30, 2013.
17. IVIG HCA Pharmacy Protocol. ASHP website. http://www.ashp.org/s_ashp/docs/files/DShort_IVIGHCAPharmacyProtocol.doc
. Updated 1995. Accessed October 19, 2013.
18. Research and markets: immunoglobulins market to 2019. Wall Street Journal website.
Updated May 20, 2013. Accessed October 19, 2013.
19. Loeffler DA. Intravenous immunoglobulin and Alzheimer’s disease: what now.
J Neuroinflammation. 2013;10(1):70.
20. Leong H, Stachnik J, Bonk ME, Matuszewski KA. Unlabeled uses of intravenous
immune globulin. Am J Health Syst Pharm. 2008;65(19):1815-1824.
21. Aston L, McNae A, Taylor J. The effect of ideal body weight adjusted dosing
on the use of intravenous immunoglobulin in Western Australia. Australian Red Cross
Blood Service website. http://www.transfusion.com.au.
Accessed September 30, 2013.
22. Chow S, Salmasi G, Callum JL, Lin Y. Trimming the fat with an IVIG approval
process. Transfus Apher Sci. 2012;46(3):349-52.
Prepared by: Aparna Reddy, PharmD
PGY-2 Drug Information Specialty
University of Illinois at Chicago