Amy E. Clarke, DNP, RN, IgCN®
Chief Clinical Officer
Immunoglobulin National Society
Calabasas, California
Luba Sobolevsky, PharmD, IgCP®
President and CEO
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/mLFDA-labeled indications
20200PI, CIDP (single product approval)
16.5165PI
10100PI
10 + rHuPH20100PI, 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

image
Figure 1. Conventional SCIG (10%, 16.5%, and 20%) administration sites.a
SCIG, subcutaneous immunoglobulin.
a Abdomen, thighs, upper arms, or back and/or lateral hip
Based on references 8-14.
image
Figure 2. fSCIG administration sites.a
fSCIG, facilitated subcutaneous immunoglobulin.
a Upper or middle abdomen, upper thighs

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
RegimenPI starting dose rangeCIDP dose starting rangeClinical rationale for dose adjustment
Weekly SCIG (dosing may be calculated to infuse daily through biweekly)0.1-0.2 g/kg0.2 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 wk300-600 mg/kgSame as maintenance IVIG dosePI: 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/functionResponsibilities and monitoring activities
Pharmacist
  • Perform initial assessment: review renal/hepatic function, IgA levels, allergies, and contraindications
  • Confirm product, dose, and rate prior to each dispense
  • Monitor site reactions, leakage, pain, and weight status
  • Reassess for dosing adequacy, preventable infusion issues such as leaking, localized reactions, and need for reeducation, and evaluate dose adequacy monthly or with clinical changes
Nurse
  • Conduct baseline assessment: vital signs, screen for infection, and evaluate skin integrity
  • Provide training on technique, verify site selection, and deliver safety education
  • Follow-up by phone/telehealth within 24-72 h of first infusion or equipment/technique change
Patient
  • Monitor for changes in health status between visits
  • Report fever >100.4°F, neurologic changes, or systemic symptoms
  • Recognize site complications (eg, leakage, erythema >10 cm for >24 h)
  • Document each infusion: time, rate, site, volume, and reactions
  • Participate in teach-back and journal review to reinforce adherence
Care team
(pharmacist, prescriber, nurse)
  • Conduct huddles at therapy initiation and every 90 d
  • Evaluate dosing accuracy, outcomes, adherence, and technique
  • Adjust therapy based on clinical goals and patient feedback
  • Use formal tools (eg, infection tracking for PI, INCAT/R-ODS for CIDP) at least every 4 wk
CIDP, chronic inflammatory demyelinating polyneuropathy; fSCIG, facilitated subcutaneous immunoglobulin; Ig, immunoglobulin; INCAT, Inflammatory Neuropathy Cause and Treatment; PI, primary immunodeficiency; R-ODS, Rasch-built Overall Disability Scale.
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
IssueSuggested interventions
Site leakage
  • Use longer needles
  • Reduce flow rate
  • Use transparent dressing
  • Add an additional infusion site
Pain or firmness
  • Apply warm compresses
  • Divide volume into another site
  • Use smaller gauge needle
Persistent localized reactions
  • Rotate injection sites
  • Consider topical corticosteroid or oral antihistamine (per prescriber)
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
DomainHighlights
Site selection
  • Rotate sites on the abdomen, thighs, flank, and upper arm sites (see Figures 1 and 2); selection of site is based on diagnosis and method of administration
  • Avoid bony prominences, scars, nonintact or inflamed skin, tattoos, or areas with visible blood vessels
Supplies
  • Needle set (up to 8 needles based on product administered)
  • 1-8 infusion sites, dependent on total volume, tissue tolerance of volume and rate, and patient preference
  • 24- to 27-gauge needles (rates =50 mL/h may require high-flow needle gauge)
  • 6- to 14-mm needle length
  • Syringe driver set or pump administration set
  • Syringe driver pump (for SCIG) or infusion pump capable of titration (for fSCIG)
  • Epinephrine auto-injector
  • Sharps container
  • Adhesive bandages or medical tape
  • Topical numbing agent, if prescribed
Preparation
  • Bring vials or prefilled syringes to room temperature
  • Perform hand hygiene
  • Prepare needle sets and connect flow rate or pump administration tubing
Infusion
  • Insert needle at 90° (for 6- to 14-mm needles)
  • Limit volume per site and hourly rate based on product specifications, site tolerance, and patient preference
  • If leakage or discomfort occurs, reduce the rate or distribute volume to additional sites
Post-infusion
  • Apply gentle pressure for 30 s
  • Massage, if tolerated, to aid dispersion of fluid
  • Document lot number, dose, site selection, rate, and site reactions with each 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.

Illustrative Case Example

A 34-year-old woman (weight, 80 kg) with CVID transitioned from IVIG therapy (administered at 600 mg/kg every 4 weeks) to weekly SCIG therapy due to recurrent migraine headaches and progressive difficulty with venous access. She was prescribed 20% SCIG to be administered at a dose of 0.15 g/kg (12 g weekly) over 60 minutes into 2 abdominal sites using a spring-powered syringe pump.

Over the first 3 months of SCIG therapy, the patient demonstrated excellent adherence, confirmed by pharmacy refill records and consistent infusion log documentation. She experienced no systemic adverse events, such as headaches, nausea, fatigue, or flu-like symptoms. She did not report any local complications, such as site swelling, pain, or leakage. Her infection frequency declined, and her self-reported quality of life, as measured by the EQ-5D utility score, improved from 0.71 to 0.89.

This patient’s case highlights the importance of individualized treatment planning, proper technique training, and consistent interdisciplinary follow-up to enhance safety, adherence, and improved outcomes in SCIG therapy.

CVID, common variable immunodeficiency; EQ-5D, EuroQol 5-Dimension; IVIG, intravenous immunoglobulin; SCIG, subcutaneous immunoglobulin.

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
DomainHighlights
Multimodal instruction
  • Use of video tutorials, printed materials, and live demonstrations to reinforce proper technique and increase retention
  • Many product manufacturers (eg, those offering SCIG and fSCIG formulations) provide structured training kits and access to certified infusion nurses through sponsored support programs
Teach-back methodology
  • Patients or caregivers should demonstrate all setup and infusion steps and describe first-line troubleshooting for issues such as:
    • Site pain or swelling
    • Leakage or displacement
    • Pump interruption or alarms
Safety communication
  • Patients must be able to:
    • Identify when to contact the specialty pharmacy or prescriber for guidance
    • Recognize red-flag symptoms requiring urgent care (eg, fever >100.4°F, persistent site pain, neurologic changes, signs of systemic reaction)
Infusion tracking
  • Use of a digital or paper infusion journal to document:
    • Infusion start and stop times
    • Volume and rate administered
    • Local site reactions or systemic symptoms
Emergency planning
  • Provide written emergency instructions with 24-h contact numbers for the specialty pharmacy and prescriber, including guidance for when to seek immediate medical attention
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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  14. Gammagard Liquid. Package insert. Takeda Pharmaceuticals USA, Inc; 2024. Accessed June 23, 2025. www.shirecontent.com/PI/PDFs/Gamliquid_USA_ENG.pdf
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