Immunoglobulin National Society
Calabasas, California
Immunoglobulin National Society
Calabasas, California
Immunoglobulin (Ig) therapy, first introduced in the 1950s, began with intramuscular formulations that were limited by small volumes, frequent dosing, and significant tissue irritation.
Subsequent advances in plasma fractionation, filtration, pathogen safety, and stabilizers have led to the development of highly purified 5% and 10% intravenous immunoglobulin (IVIG), allowing higher doses to be administered under clinical supervision. Over time, these innovations paved the way for subcutaneous Ig (SCIG) and facilitated SCIG (fSCIG) products. These formulations enable patients to self-administer Ig therapy at home, promoting autonomy, flexibility, and improved quality of life.1-6
Defining SCIG and fSCIG Formulations
SCIG is available in 10%, 16.5%, and 20% concentrations. These include conventional SCIG products and a single 10% immune globulin coadministered subcutaneously (fSCig) with recombinant human hyaluronidase PH20 (rHuPH20).7-14 Table 1 outlines the current concentrations and FDA-approved indications for each formulation. For an inclusive reference listing all currently approved SCIG/fSCIG formulations and their labeled indications, see the IgNS Ig Product and Risk Factor Chart (https://ig-ns.org/product/ig-therapy-products-and-risk-factor-chart/).
Table 1. SCIG and fSCIG Formulations With Approved Indications | ||
Concentration, % | Ig, mg/mL | FDA-labeled indications |
---|---|---|
20 | 200 | PI, CIDP (single product approval) |
16.5 | 165 | PI |
10 | 100 | PI |
10 + rHuPH20 | 100 | PI, CIDP |
CIDP, chronic inflammatory demyelinating polyneuropathy; Ig, immunoglobulin; PI, primary immunodeficiency; rHuPH20, recombinant human hyaluronidase PH20; SCIG, subcutaneous immunoglobulin. Based on references 4, 8-10, and 13-16. |
Mechanism of Action and Pharmacokinetics
All IgG preparations supply exogenous antibodies that neutralize pathogens, modulate complement activation, and downregulate pro-inflammatory cytokines. Compared with IVIG, conventional SCIG yields a steadier serum concentration curve, with minimal peak-to-trough fluctuations. The bioavailability of SCIG typically ranges from 65% to 69%, and steady state is achieved after 2 to 3 weekly infusions. fSCIG coadministered with rHuPH20 enhances tissue permeability and absorption, resulting in more than 92% bioavailability and allowing 3- to 4-week dosing intervals with similar IgG trough levels comparable to IVIG.1,3,4,8-10,13-16
Indications and Patient Selection
All conventional SCIG and fSCIG formulations are approved for primary immunodeficiency (PI); one 20% conventional SCIG and the fSCIG product are approved for chronic inflammatory demyelinating polyneuropathy (CIDP). Candidates for SCIG/fSCIG include individuals with poor venous access, a desire for autonomy, poor IVIG tolerability, or significant quality-of-life disruption with IVIG. As with IVIG, contraindications of SCIG and fSCIG include IgA deficiency with IgE anti-IgA antibodies or hypersensitivity to any component of the formulation. Product selection should be based on shared decision-making, and the patient’s preference, lifestyle, comorbidities, and insurance coverage should be considered.1,3,4,7-16
Dosing Strategies
Two practical, evidence-based approaches guide initial SCIG dosing: weight-based initiation and conversion from IVIG to SCIG.
The weight-based method starts at an ideal body weight of 0.15 g/kg weekly for PI and 0.2 g/kg weekly for CIDP (20% SCIG only), and then is adjusted to maintain infection control and appropriate serum IgG levels (in PI) or symptom improvement/stabilization (in CIDP).
The IVIG-to-SCIG dose conversion method (20% and 10% SCIG) divides the patient’s total monthly IVIG dose by 4 to obtain a weekly dose. The dose adjustment factor of 1.37 is used to compensate for the lower bioavailability of SCIG, resulting in the target weekly dose. In clinical practice, prescribers may opt for a 1:1 conversion factor when transitioning from IVIG to SCIG.
When dosing fSCIG, the patient should be on stable doses of IVIG. The maintenance dosing and frequency of fSCIG should be the same as the patient’s previous IVIG treatment (the typical dosing interval range being every 2-4 weeks).1,3,4,7-14
Table 2 presents typical starting dose ranges and the clinical rationale for subsequent dose adjustments.
Table 2. Evidence-Based Starting Doses and Adjustment Triggers | |||
Regimen | PI starting dose range | CIDP dose starting range | Clinical rationale for dose adjustment |
---|---|---|---|
Weekly SCIG (dosing may be calculated to infuse daily through biweekly) | 0.1-0.2 g/kg | 0.2 g/kg, increasing to 0.4 g/kg | PI: =2 infections in 6 mo CIDP: clinical decline as indicated by patient-reported outcome measures |
fSCIG every 3-4 wk | 300-600 mg/kg | Same as maintenance IVIG dose | PI: breakthrough infections CIDP: functional decline |
CIDP, chronic inflammatory demyelinating polyneuropathy; fSCIG, facilitated subcutaneous immunoglobulin; Ig, immunoglobulin; IVIG, intravenous immunoglobulin; PI, primary immunodeficiency. Based on references 1, 4, 8-10, and 13-16. |
Risk Assessment, Ongoing Clinical Monitoring, and Interdisciplinary Care Planning
Interdisciplinary care planning is essential to minimize preventable adverse reactions during and after SCIG/fSCIG therapy. Each team member—pharmacist, nurse, prescriber, and patient—plays a defined role in promoting safe and effective long-term administration. Ongoing interdisciplinary communication paired with empowered patient self-monitoring is critical for safe and sustainable SCIG therapy (Table 3).1
Table 3. Interdisciplinary Roles and Monitoring Responsibilities In SCIG/fSCIG Therapy | |
Role/function | Responsibilities and monitoring activities |
---|---|
Pharmacist |
|
Nurse |
|
Patient |
|
Care team (pharmacist, prescriber, nurse) |
|
CIDP, chronic inflammatory demyelinating polyneuropathy; fSCIG, facilitated subcutaneous immunoglobulin; Ig, immunoglobulin; INCAT, Inflammatory Neuropathy Cause and Treatment; PI, primary immunodeficiency; Based on reference 1. |
ADRs and Risk Mitigation Strategies
Adverse drug reactions (ADRs) are possible with SCIG and fSCIG therapy but generally mild and subside after the first few infusions. Local site reactions, such as erythema, swelling, or pruritus, typically peak within eight hours of administration and often resolve after 2 to 3 treatment cycles. Conservative management includes the use of cold compresses, nonsedating antihistamines, and rotating infusion sites to minimize recurrence.1,3-14
Systemic ADRs, including headache, nausea, or fatigue, are less common with SCIG than with IVIG, but they may occur with either conventional SCIG or fSCIG. Higher monthly doses, such as those used with fSCIG, may increase the likelihood of these effects. Although rare, serious complications such as aseptic meningitis, thromboembolic events, and hemolysis have been reported with both SCIG and fSCIG and warrant prompt evaluation and possible transition to an alternate preparation (Table 4).1,3-14
Table 4. Common SCIG/fSCIG Adverse Effects and Suggested Interventions | |
Issue | Suggested interventions |
---|---|
Site leakage |
|
Pain or firmness |
|
Persistent localized reactions |
|
fSCIG, facilitated subcutaneous immunoglobulin. Based on references 1 and 3-16. |
Administration Fundamentals And Best Practices
Safe and effective SCIG/fSCIG administration depends on 4 integrated domains: site selection, supplies, preparation, and infusion technique. A well-structured approach across these areas reduces preventable infusion-related adverse events and ensures consistent therapeutic outcomes (Table 5).1,7-16
Table 5. Best–Practice Checklist for SCIG and fSCIG Administration | |
Domain | Highlights |
---|---|
Site selection |
|
Supplies |
|
Preparation |
|
Infusion |
|
Post-infusion |
|
fSCIG, facilitated subcutaneous immunoglobulin. Based on references 1, 4, 8-10, and 13-16. |
Site selection
Appropriate sites include the abdomen, thighs, upper arms, and flanks, with attention to tissue integrity, previous reactions, and patient comfort. Rotating sites with each infusion reduces the risk for local inflammation, scarring, and thickening of subcutaneous fatty tissue, which can affect absorption.
Supplies
Needle length and angle are chosen based on patient body habitus and product guidelines:
- 6- to 14-mm needles: Insert at a 90-degree angle.
- This technique is supported by manufacturer training guides and validated clinical checklists.
Preparation
Dry priming (pushing solution to the needle hub without wetting the tip) helps eliminate air and minimizes local irritation by reducing histamine release at the injection site. All preparations should be conducted aseptically with visual inspection of the product for clarity and expiration.
Infusion technique and monitoring
The infusion rate and volume must align with the product label, patient age/weight, and prior tolerance. Starting with conservative rates and escalating slowly minimize systemic ADRs.
Patients should be observed during initial infusions, especially when transitioning from IVIG or increasing doses.
Technique-related issues, such as needle dislodgement, high back pressure, leakage, or tissue resistance, can cause discomfort, swelling, and underdosing. These should be addressed during nurse training and reinforced at follow-up.
Common preventable ADRs include pain from improper angle/depth, delayed leakage from unstable needle placement, and extended erythema due to rapid delivery. Interventions include slowing the rate, changing sites, or modifying the needle length/angle.
Documentation
Complete, real-time documentation should include:
- product lot number;
- dose and volume per site;
- programmed rate and total infusion time;
- injection site(s) used; and
- local or systemic reactions observed.
Proper monitoring and meticulous technique during SCIG/fSCIG delivery reduce avoidable complications and support consistent patient outcomes.
Equipment and Supply Selection
Infusion pumps may include FDA-approved non–battery syringe drivers (for SCIG) or peristaltic pumps with programmable pressure limits and occlusion alarms (for SCIG/fSCIG), which maintain a constant flow regardless of viscosity. Needle sets range from single- to multi-leg configurations. Transparent dressings permit visualization without disturbing the site. Patient hypersensitivity to ancillary supply components must be considered when selecting a product.1,3
Training and Transition to Self-Administration
A combination of educational strategies, including video-based instruction, hands-on training, and manufacturer-supported programs, has been shown to streamline the transition to independent self-administration of SCIG and fSCIG, often within 3-4 sessions. Studies have demonstrated that most patients or caregivers can safely and confidently self-administer therapy after 3 to 4 structured training visits.1,7-18
Effective patient education should include the following the components outlined in Table 6.1,7-18
Table 6. Key Components of Effective Patient Education | |
Domain | Highlights |
---|---|
Multimodal instruction |
|
Teach-back methodology |
|
Safety communication |
|
Infusion tracking |
|
Emergency planning |
|
fSCIG, facilitated subcutaneous immunoglobulin. Based on references 1 and 7-18. |
When implemented systematically, this approach supports patient autonomy, improves adherence, and reduces preventable complications during SCIG/fSCIG therapy.
Conclusion
Subcutaneous Ig therapy, including both SCIG and fSCIG formulations, offers patients a flexible, self-directed alternative to IV administration. With proper product selection, evidence-based dosing strategies, and a robust training and monitoring framework, SCIG and fSCIG therapies can optimize clinical outcomes, minimize adverse effects, and support long-term adherence.
Pharmacists, nurses, prescribers, and patients must collaborate to ensure that therapy is personalized, well tolerated, and responsive to evolving clinical needs. As the field continues to evolve, ongoing research and practice innovations will further refine SCIG delivery and enhance the quality of care for individuals with PI and CIDP.
The authors reported no relevant financial disclosures.
References
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- Gamunex-C. Package insert. Grifols Therapeutics LLC; 2024. Accessed July 16, 2025. https://www.gamunex-c.com/documents/648456/5516391/Gamunex-C+Prescribing+Information.pdf
- Gammagard Liquid. Package insert. Takeda Pharmaceuticals USA, Inc; 2024. Accessed June 23, 2025. www.shirecontent.com/PI/PDFs/Gamliquid_USA_ENG.pdf
- Cutaquig. Package insert. Octapharma USA, Inc; 2024. Accessed July 14, 2025. www.cutaquig.com/pdf/PrescribingInformation.pdf
- Gammaked. Package insert. Grifols Therapeutics LLC; 2022. Accessed July 16, 2025. https://www.gammaked.com/downloads/Gammaked_Package_Insert_2022_Letter.pdf
- Moral P, et al. Front Immunol. 2025;15:1527514.
- Murphy E, et al. J Infus Nurs. 2021;44(5):289-297.
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