Is there a difference or increased risk of skin staining with Venofer if given as an infusion vs. IV push? Is it more likely to occur in certain patient populations?

Comment by InpharmD Researcher

The literature evaluating skin staining with intravenous (IV) iron therapy is limited and largely descriptive. Skin staining is characterized as an uncommon extravasation-related adverse reaction, with reported rates generally ranging from 0.68% to 1.3%, most clearly quantified for ferric carboxymaltose but also reported for other IV iron formulations, including iron sucrose (Venofer). Iron sucrose product labeling lists skin or injection-site discoloration following extravasation documented in postmarketing reports, consistent with other IV iron formulations. Available data on skin staining associated with IV iron sucrose is limited to descriptive case reports of extravasation following IV infusion administration, and comparative studies on skin staining rates with IV push vs IV infusion administration of iron sucrose were not identified. Given limitations of the available literature, patient populations or demographics at greatest risk cannot be identified or quantified at this time; however, it is reasonable to expect that those demographics with routine usage of IV iron sucrose (e.g., patients with iron-deficiency anemia or anemia of chronic kidney disease) may carry a higher risk of this adverse reaction.
Background

A 2020 review describes skin staining as an uncommon but recognized adverse effect of intravenous (IV) iron that occurs following extravasation and may be permanent. Clinical trial data cited in the article report skin discoloration rates with IV iron preparations ranging from 0.68% to 1.3%, while postmarketing surveillance suggests lower reported rates, acknowledging likely underreporting. A review of the French pharmacovigilance database (2000 to 2016) identified 51 cases of cutaneous pigmentation associated with iron; reports from the Australian adverse event database (2014 to 2019) documented 27 cases with ferric carboxymaltose and 8 cases with iron polymaltose, while no cases with iron sucrose were documented in this database. The authors emphasize that skin staining is cosmetically significant, warrants informed consent, and is best prevented through appropriate cannulation, close monitoring, and immediate cessation of infusion if extravasation is suspected. [1]

However, an earlier 2015 review evaluating the safety profile of IV iron formulations reported that, based on pooled phase II/III clinical trial data in 5,799 patients exposed to IV ferric carboxymaltose, injection-site reactions (defined as discoloration, extravasation, or pain) occurred in 1.6% of ferric carboxymaltose patients vs 1.8% of patients receiving other IV iron formulations, including iron sucrose, ferric gluconate, and iron dextran. The review notes that injection-site discoloration may be long-lasting and cosmetically concerning, but occurs across intravenous iron products rather than being unique to a specific formulation. Unfortunately, rates of skin reactions specific to IV iron sucrose could not be derived, as adverse reaction rates for all non-ferric carboxymaltose IV iron formulations were reported collectively. Similarly, injection-site reactions were also reported collectively, thus the specific incidence of skin discoloration/staining vs other injection-site reactions was not able to be identified. [2]

According to the Food and Drug Administration Adverse Event Reporting System (FAERS) database, as of September 14, 2026, skin discoloration reports within the skin and subcutaneous tissue disorders category included 93 cases associated with iron sucrose, of which 72 were classified as serious and no reported deaths, with reports submitted between 2003 and 2025. Given the nature of FAERS as a passive, voluntary reporting system with potential underreporting, duplicate submissions, and variable data quality, these counts reflect reported cases rather than true incidence rates and do not establish causality. [3]

Background References: [1] Canning M, Grannell L. A stain on iron therapy. Aust Prescr. 2020;43(5):160-163. doi:10.18773/austprescr.2020.051
[2] Friedrisch JR, Cançado RD. Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia. Rev Bras Hematol Hemoter. 2015;37(6):400-405. doi:10.1016/j.bjhh.2015.08.012
[3] U.S. Food and Drug Administration. FDA Adverse Event Reporting System (FAERS) Public Dashboard. Accessed September 14, 2026. https://fis.fda.gov/sense/app/95239e26-e0be-42d9-a960-9a5f7f1c25ee/sheet/33a0f68e-845c-48e2-bc81-8141c6aaf772/state/analysis
Relevant Prescribing Information

6.2 Adverse Reactions from Post-Marketing Experience [4]
Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.

Relevant Prescribing Information References: [4] Venofer (iron sucrose injection). Prescribing information. American Regent; March 2026.
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there a difference or increased risk of skin staining with Venofer if given as an infusion vs. IV push? Is it more likely to occur in certain patient populations?

Level of evidence

D - Case reports or unreliable data  Read more→


Please see Tables 1-2 for your response.

 

A permanent tan from iron

Design

 Case report

Case presentation

 A 68-year-old Caucasian female patient with a history of type II diabetes mellitus and chronic kidney disease stage 4 was found to have iron deficiency anemia and subsequently treated with intravenous (IV) iron sucrose. Following extensive extravasation of IV iron, she developed a permanent ‘suntan’ discoloration of her right arm, which persisted for 6 months. Despite the pigmentation, the patient was completely asymptomatic. 

Study Author Conclusions

Iron deposition is known to cause hyperpigmentation in hemochromatosis patients (‘bronze diabetes’). This is the first report of skin pigmentation developing from extravasation of IV iron sucrose, per the authors' conclusion. 

This short case report supports skin discoloration as a rare and potentially benign adverse reaction associated with IV iron sucrose therapy, but the report is limited in its documentation (i.e., number of doses given prior to the skin reaction, use of IV push vs IV infusion for all doses, actual mg dosage administered per treatment). However, it can be inferred from the reporting that this rare adverse reaction is an extravasation-related occurrence resulting from administration via IV infusion.
Table 1 References:
[5] Lim R, Irvine T, Ahmed MS, Abraham K, Wong CF. A permanent tan from iron. Kidney Int. 2008;73(7):898. doi:10.1038/sj.ki.5002649

 

Successful treatment with 532-nm Q-switched Nd:YAG laser of cutaneous siderosis following intravenous iron extravasation

Design

 Case report

Case presentation

A 65-year-old female patient with chronic anemia secondary to gastric polyposis underwent intravenous (IV) iron sucrose (Venofer®) therapy. During her third infusion session, an inadvertent paravenous injection led to extensive extravasation of iron sucrose. This complication resulted in a permanent brownish hyperpigmentation localized to the elbow crease and extending to the forearm, measuring approximately 10 x 9 x 15 cm, consistent with cutaneous siderosis. The discoloration persisted for one year prior to referral to dermatology.

Treatment commenced conservatively with a test session using a 532 nm Q-switched Nd:YAG laser (Alex Tradvantage®, Syneron/Candela). Topical anesthesia with prilocaine-lidocaine cream was administered to improve patient comfort. Post-laser care involved topical trolamine ointment. Immediately following treatment, purpura developed with crusting evident by day two; both resolved within two weeks without sequelae. Clinical evaluation at two months post-initial session demonstrated marked improvement in the treated pigmented area. Subsequently, four additional laser treatments were administered at two-month intervals.

Six months following the final session, near-complete resolution of hyperpigmentation was observed without evidence of scarring or dyschromia. The patient expressed satisfaction with the cosmetic outcome.

Study Author Conclusions

The 532 nm Q-switched Nd:YAG laser is an effective and safe treatment option for cutaneous siderosis due to intravenous iron extravasation.

Althought this study is limited by its single-patient case report design, limiting broader generalizability, it provides valuable insight into a potential treatment for a rare condition resulting from extravasation or inadvertent IV administration with significant cosmetic impact. The report does not note whether IV push iron sucrose has been associated with similar iron-deposit hyperpigmentation of the skin.
Table 2 References:
[6] Hammami Ghorbel H, Lacour JP, Passeron T. Successful treatment with 532-nm Q-switched Nd:YAG laser of cutaneous siderosis following intravenous iron extravasation. J Eur Acad Dermatol Venereol. 2015;29(4):818-819. doi:10.1111/jdv.12417