Explore Safety Evaluated in Multiple Major Studies1
Systemic AEs
Side effects commonly seen with IVIg occurred at a lower rate with Hizentra1,2
Lower incidence of systemic AEs compared to IVIg in a pooled analysis of 7 clinical studies (N=125).1
Systemic AEs included fatigue, vomiting, fever, headache, and nausea.
POOLED ANALYSIS
~10x
Lower incidence of systemic AEs1
≤0.22 events/infusion with IVIg vs ≤0.00915 events/infusion with Hizentra.
This indirect comparison was not part of a randomized, head-to-head trial; results should be interpreted with caution.
Local reactions
Most local reactions were mild and decreased over time
Across all 7 studies, the most common treatment-related AEs were injection site reactions (2919 events; 0.001-0.592 AEs per infusion).1
US PIVOTAL STUDY
93.4%
OF LOCAL REACTIONS
WERE MILD AND DID NOT INTERFERE WITH ROUTINE ACTIVITIES2
EUROPEAN PIVOTAL STUDY*
- Local reactions, often associated more with SCIg than IVIg, decreased over time from ~20% to <5% during the efficacy period3
- Patients rated local tolerability as “good/very good” for 96.5% of infusions3
*In a prospective, open-label, single-arm, Phase 3 European study, the safety and efficacy of weekly Hizentra were evaluated for 10 months (3-month wash-in/wash-out period followed by a 7-month efficacy period) in 51 subjects with PI who had been treated previously with IVIg every 3 or 4 weeks or with SCIg weekly.3
Common Aes
Clinically established tolerability for Hizentra2
Most common AEs (experienced by ≥5% of patients; ITT population; US study)
| All events | Temporally associated (72 hours) | |
|---|---|---|
| No. (%) of patients (n=49) | No. (rate) of events (n=2264) | |
| Any AE | 49 (100) | 1749 (0.773) |
| Injection site reaction | 49 (100) | 1314 (0.580) |
| Sinusitis | 14 (28.6) | 20 (0.009) |
| Headache | 13 (26.5) | 40 (0.018) |
| Nasopharyngitis | 11 (22.4) | 15 (0.007) |
| Cough | 8 (16.3) | 9 (0.004) |
| Diarrhea | 7 (14.3) | 8 (0.004) |
| Bronchitis | 6 (12.2) | 9 (0.004) |
| Fatigue | 6 (12.2) | 6 (0.003) |
| Injection site bruising | 5 (10.2) | 19 (0.008) |
| Back pain | 5 (10.2) | 11 (0.005) |
| Acute sinusitis | 5 (10.2) | 7 (0.003) |
| Nausea | 5 (10.2) | 5 (0.002) |
| Abdominal pain upper | 5 (10.2) | 5 (0.002) |
| Upper respiratory tract infection | 5 (10.2) | 6 (0.003) |
| Rash | 5 (10.2) | 7 (0.003) |
| All events | Temporally associated (72 hours) | |
|---|---|---|
| No. (%) of patients (n=49) | No. (rate) of events (n=2264) | |
| Any AE | 49 (100) | 1566 (0.692) |
| Injection site reaction | 49 (100) | 1298 (0.573) |
| Sinusitis | 7 (14.3) | 10 (0.004) |
| Headache | 12 (24.5) | 32 (0.014) |
| Nasopharyngitis | 8 (16.3) | 8 (0.004) |
| Cough | 5 (10.2) | 6 (0.003) |
| Diarrhea | 5 (10.2) | 6 (0.003) |
| Bronchitis | 5 (10.2) | 6 (0.003) |
| Fatigue | 4 (8.2) | 4 (0.002) |
| Injection site bruising | 5 (10.2) | 18 (0.008) |
| Back pain | 4 (8.2) | 5 (0.002) |
| Acute sinusitis | 4 (8.2) | 5 (0.002) |
| Nausea | 4 (8.2) | 4 (0.002) |
| Abdominal pain upper | 3 (6.1) | 3 (0.001) |
| Upper respiratory tract infection | 3 (6.1) | 3 (0.001) |
| Rash | 2 (4.1) | 3 (0.001) |
LOW DISCONTINUATION RATE
2 patients withdrew from the US pivotal study due to AEs, a discontinuation rate of 4.1%. Both AEs were considered at least possibly related to Hizentra.2
REAL-WORLD DATA
Real-world data support the established safety profile of Hizentra4
- Safety data from real-world postmarketing reports (N=35,255)† across all reporter-designated indications are consistent with the safety profile established in controlled clinical trials
- The most frequently reported AEs were injection site reactions (32%), headache (11.7%), and fatigue (8.9%)
- The estimated overall rates of reported thromboembolic events and infections were 0.18 and 0.63 per 100 patient years, respectively, for the immunodeficiency population
†While spontaneous reports can be useful in signal detection and characterization of an AE, there are limitations associated with the use of postmarketing pharmacovigilance data, including reliance on reporters to register an AE, underreporting, reporting bias, lack of exposure data for risk and rate estimates, and ascertainment bias.
A long legacy of clinical use
>16years of patient experience
19M+doses delivered worldwide5‡
‡Estimated doses based on grams of Hizentra sold worldwide from 2010 through June 2026.
Abbreviations: AE, adverse event; CIDP, chronic inflammatory demyelinating polyneuropathy; ITT, intention-to-treat; IVIg, intravenous immunoglobulin; PI, primary immunodeficiency; SCIg, subcutaneous immunoglobulin.
References: 1. Jolles S, Rojavin MA, Lawo JP, et al. J Clin Immunol. 2018;38(8):864-875. doi:10.1007/s10875-018-0560-5 2. Hagan JB, Fasano MB, Spector S, et al. J Clin Immunol. 2010;30(5):734-745. doi:10.1007/s10875-010-9423-4 3. Jolles S, Bernatowska E, de Gracia J, et al. Clin Immunol. 2011;141(1):90-102. doi:10.1016/j.clim.2011.06.002 4. Sawyer C, Radu A, Hubsch A, Katkade V. Safety of decade plus use of IgPro20 in the real world: post-marketing pharmacovigilance report. Poster: CSL Behring; 2024. Accessed November 5, 2025. https://medicalaffairs.cslbehring.com/-/media/medical-affairs/documents/posters/hizentra/hizentra_long-term-safety-_poster_100051_csl-medical-affairs.pdf 5. Data on File. Available from CSL Behring as DOF HIZ-005.
IMPORTANT SAFETY INFORMATION
WARNING: Thrombosis may occur with immune globulin products, including Hizentra. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors.
For patients at risk of thrombosis, administer Hizentra at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.
Hizentra is contraindicated in patients with a history of anaphylactic or severe systemic reaction to human immune globulin (Ig) or components of Hizentra (eg, polysorbate 80), as well as in patients with immunoglobulin A deficiency with antibodies against IgA and a history of hypersensitivity. Because Hizentra contains L-proline as stabilizer, use in patients with hyperprolinemia is contraindicated.
IgA-deficient patients with anti-IgA antibodies are at greater risk of severe hypersensitivity and anaphylactic reactions. Thrombosis may occur following treatment with Ig products, including Hizentra.
Monitor patients for aseptic meningitis syndrome (AMS), which may occur following treatment with Ig products, including Hizentra. In patients at risk of acute renal failure, monitor renal function, including blood urea nitrogen, serum creatinine and urine output. In addition, monitor patients for clinical signs of hemolysis or pulmonary adverse reactions (eg, transfusion-related acute lung injury [TRALI]).
Hizentra is derived from human blood. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), cannot be completely eliminated.
The most common adverse reactions (observed in ≥5% of study subjects) were local infusion-site reactions, as well as headache, diarrhea, fatigue, back pain, nausea, extremity pain, cough, upper respiratory tract infection, rash, pruritus, vomiting, upper abdominal pain, migraine, arthralgia, pain, fall, and nasopharyngitis.
The passive transfer of antibodies can interfere with response to live virus vaccines and lead to misinterpretation of serologic test results.
Indications
Hizentra®, Immune Globulin Subcutaneous (Human), 20% Liquid, is indicated for:
- Treatment of primary immunodeficiency (PI) in adults and pediatric patients 2 years and older.
- Maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment.
- Limitation of Use: Maintenance therapy in CIDP has been systematically studied for 6 months and for a further 12 months in a follow-up study. Continued maintenance beyond these periods should be individualized based on patient response and need for continued therapy.
For subcutaneous infusion only.
Please see full Prescribing Information for Hizentra including boxed warning.
To report SUSPECTED ADVERSE REACTIONS, contact the CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Hizentra is manufactured by CSL Behring AG and distributed by CSL Behring LLC.
Hizentra® is a registered trademark of CSL Behring AG.
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