Injection Site Reaction

Adverse reactions that occur initially at the site of injection or infusion. Milder type is confined to a local allergic flare reaction. A more severe reaction is caused by extravasation of VESICANTS from the blood vessel at the site of injection and can cause damage to the surrounding tissue. In tumor flare reaction symptoms involve well beyond the injection site such as an increase in the tumor size and tumor markers levels, bone pain, and HYPERCALCEMIA.

Also Known As:

Networked: 1253 relevant articles (25 outcomes, 117 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Psoriasis (Pustulosis Palmaris et Plantaris)
2.	Pain (Aches)
3.	Infections
4.	Vomiting
5.	Delayed Hypersensitivity (Hypersensitivity, Type IV)

Experts

1.	Kastelein, John J P: 11 articles (09/2020 - 08/2007)
2.	Halperin, Scott A: 11 articles (05/2019 - 01/2002)
3.	Yancopoulos, George D: 10 articles (01/2020 - 08/2008)
4.	Baccara-Dinet, Marie T: 9 articles (10/2020 - 09/2014)
5.	Pirozzi, Gianluca: 9 articles (01/2020 - 06/2013)
6.	Keating, Gillian M: 9 articles (06/2016 - 01/2002)
7.	Graham, Neil M H: 8 articles (01/2020 - 07/2016)
8.	Stahl, Neil: 8 articles (01/2020 - 08/2008)
9.	Pordy, Robert: 8 articles (11/2018 - 07/2012)
10.	Blauvelt, Andrew: 7 articles (09/2021 - 12/2016)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Injection Site Reaction:

1.	VaccinesIBA 02/01/2018 - "Adverse effects were primarily injection site reactions and flu-like symptoms under grade 2. The efficacy of vaccines defined by regression of CIN2/3 to no CIN or CIN1 ranged from 17 to 59% following a minimum of a 12-week follow-up. " 12/05/2017 - "Systemic and injection site reactions were mild, transient, and similar in each group, whereas none of the spontaneously reported adverse events, serious or nonserious, were considered related to study vaccine. " 12/01/2000 - "All study vaccines were well-tolerated, and the rates of systemic and injection site reactions were similar between groups. " 11/01/2023 - "In the reactogenicity subset with available data, solicited reactions (solicited injection-site reactions and solicited systemic reactions) within 7 days after any injection occurred in 1398 (57·8%) of 2420 vaccine recipients and 983 (40·9%) of 2403 placebo recipients. " 01/01/2023 - "Injection site reactions consisted mainly of swelling reactions, which were more frequent, more pronounced and long-lasting in the adjuvanted vaccine group. "
2.	Omalizumab (Xolair)FDA Link 01/13/2014 - "Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab).To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. " 07/01/2013 - "Omalizumab was generally well tolerated in clinical trials; the most common adverse event was transient injection-site reactions. " 01/01/2009 - "In addition, the overall incidence of drug-related adverse events and injection site reactions in the re-treatment study did not increase compared with those in the omalizumab group in the core study. " 01/01/2008 - "Injection-site reactions were the most commonly reported adverse events in clinical trials with omalizumab. " 11/01/2022 - "Results: The most common adverse effect of omalizumab treatment was injection-site reactions (4.7%) in both groups. "
3.	Enfuvirtide (Fuzeon)FDA Link 01/01/2010 - "The fusion inhibitor enfuvirtide has demonstrated efficacy in heavily treatment-experienced patients, although injection-site reactions can be problematical. " 07/01/2008 - "The aim of this study was to evaluate the quality of life and the intensity of the injection site reactions during the first 6 months of treatment with enfuvirtide according to the counseling and training provided by nurses and physicians. " 01/01/2008 - "A randomized study to evaluate injection site reactions using three different enfuvirtide delivery mechanisms (the OPTIONS study)." 01/01/2008 - "This study correlated the clinical and histopathological pattern of injection-site reactions (ISRs) to the pharmacokinetics of enfuvirtide in patients with HIV. " 10/01/2012 - "Enfuvirtide and cutaneous injection-site reactions."
4.	Adalimumab (Humira)FDA Link 01/01/2021 - "In this study, we analyzed the data obtained from the 'Rete Nazionale di Farmacovigilanza' (Pharmacovigilance National Network) to investigate whether, and to what extent, the differences in the formulation of the various adalimumab versions had an impact on the rate of injection site reactions reported in Italy in the period 2016-2019. " 09/01/2008 - "To our knowledge, there have been no published studies on immunologic mechanism of injection site reactions to adalimumab to date. " 01/01/2021 - "Relationship between injection site reactions and different adalimumab formulations. " 11/01/2020 - "The most commonly reported adalimumab adverse event was injection-site reaction. " 12/01/2017 - "Cephalea and injection site reactions were more prevalent in adalimumab patients. "
5.	Glatiramer Acetate (Copaxone)FDA Link 07/06/2015 - "Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a), SC IFNb-1b, glatiramer acetate), the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. " 01/01/2004 - "However, efficacy of blinding should be balanced against well-known side effects, including injection-site reactions in glatiramer acetate-treated patients. " 11/01/2016 - "Given the relatively short duration of trials leading to FDA approval of thrice weekly dosing of glatiramer acetate, clinicians should perform careful clinical and histopathological evaluation and reporting of patients who experience injection site reactions." 05/12/2010 - "Local injection-site reactions were observed in up to a half of patients treated with glatiramer acetate, thus making a blind assessment of outcomes questionable. " 10/31/2009 - "The most common adverse events in the glatiramer acetate group were injection-site reactions (135 [56%] glatiramer acetate vs 56 [24%] placebo) and immediate post-injection reactions (47 [19%] vs 12 [5%]). "
6.	dupilumabIBA 11/14/2023 - "Dupilumab was the only biologic associated with injection-site reactions (7.98%, ROR = 8.17, 95% CI: 7.98, 8.37). " 11/01/2023 - "The most common treatment-emergent adverse events were injection-site reactions (ten [14%] in the weekly dupilumab/weekly dupilumab group and four [11%] in the placebo/weekly dupilumab group). " 04/01/2023 - "We present a case of delayed hyperpigmented injection site reactions following chronic dupilumab use." 04/01/2023 - "The most common adverse reactions from dupilumab use are temporary injection site reactions and ocular surface reactions; however, a variety of both acute and delayed cutaneous reactions have also been described. " 04/01/2023 - "Delayed Hyperpigmented Injection Site Reactions Due to Chronic Dupilumab Use."
7.	Infliximab (Remicade)FDA Link 02/01/2015 - "There may be an advantage from the PEGylated formulation of CZP in terms of reduced injection-site reactions, reduced placental transfer in pregnancy and as a treatment option in patients who are unable to tolerate infliximab." 01/01/2011 - "One of the more common adverse effects continues to be infusion or injection-site reactions, although children tend to have a lower rate of infusion reactions with infliximab compared to adults. " 02/01/2014 - "All six patients showed improvement in their psoriasis after the initiation of infliximab and no significant tolerability issues or injection site reactions were reported, despite the presence of several comorbid conditions or patient characteristics that traditionally reduce the efficacy of psoriasis treatments. " 08/01/2013 - "For adverse reactions, there were also no significant differences except for injection site, reactions which were more frequent with etanercept, with a mean difference of 26% relative to infliximab. " 05/01/2013 - "There have also been a number of reports of the development of anti-drug antibodies, of which those against infliximab can interfere with the drug's pharmacokinetics (and therefore its effects), and may also cause acute and delayed infusion and injection site reactions. "
8.	LipidsIBA 02/05/2009 - "Subcutaneous administration of lipid-formulated live or HK 316F-induced significantly fewer adverse injection site reactions than Gudair; adverse injection site reactions were eliminated altogether by intraperitoneal (i.p.) injection of lipid-formulated live 316F. " 03/01/2015 - "Mipomersen resulted in a significant improvement in lipid parameters except for HDL-C and increased the risks of injection-site reactions, flu-like symptoms, and hepatic steatosis compared with placebo." 11/01/2022 - "The most common adverse reactions to rilonacept include injection-site reactions, upper respiratory tract infections, and increased lipids. " 04/23/2022 - "The safety profile of most current RNA-based lipid therapies is acceptable but adverse events associated with various therapies targeting lipid pathways have included injection site reactions, inflammatory reactions, hepatic steatosis and thrombocytopenia. "
9.	Etanercept (Enbrel)FDA Link 06/01/1999 - "Injection site reactions occurred more frequently in etanercept- than placebo-treated patients, but did not bias the results of any study. " 01/28/1999 - "The only adverse events associated with etanercept were mild injection-site reactions, and no patient withdrew from the study because of adverse events associated with etanercept. " 09/01/2021 - "Injection site reactions occurred in 67.7% and 66.0% of subjects treated with EtaBS and etanercept, respectively. " 01/01/2018 - "Also, all 11 patients who stopped etanercept with injection site reactions were receiving a single use prefilled syringe. " 07/01/2017 - "Etanercept showed the highest risk to develop infusion site reaction (RR: 5.33, NNH: 4.65). "
10.	InterferonsIBA 07/01/2020 - "Large randomized controlled clinical trials have confirmed the efficacy of interferons for the treatment of relapsing MS. The most frequent adverse events in patients receiving IFNs include injection site reactions and flu-like symptoms. " 07/01/2022 - "So far, various side effects have been reported in connection with interferon use, including lupus-like reaction, which is relatively rare and classified as an injection-site reactions (ISR). " 04/01/2021 - "However, the use of an interferon may lead to flu-like symptoms (FLS) and injection-site reactions (ISR) that results in drug discontinuation. " 03/01/2012 - "Known features of lupus-like reactions at SC interferon-α injection sites are reviewed, and cutaneous injection site reactions to SC interferon-α are summarized." 09/01/2005 - "Classical systemic side effects related to all beta interferons can effectively be managed by dose escalation, and the use of an autoinjector minimises injection site reactions. "

Therapies and Procedures

1.	Therapeutics 04/01/2015 - "Efficacy of combination light-emitting diode (635 and 830 nm) therapy in treating local injection-site reactions after filler." 01/01/2020 - "Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. " 01/01/2023 - "Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. " 10/01/2021 - "The most common side effect is represented by local skin injection site reactions after 1-2 weeks of therapy. " 11/01/2018 - "Injection site reactions (ISRs) and other adverse side effects are commonly observed during therapy with biologics. "
2.	Injections 07/01/2023 - "A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections." 03/28/2023 - "Four of 328 injections were associated with an injection-site reaction (1%). " 11/01/2021 - "Injection site reactions were the most common adverse event, occurring after 914 (21%) of 4442 injections in the extension switch population and 3732 (21%) of 17 392 injections in the randomly assigned long-acting group. " 01/01/2021 - "Three-fourths experienced gastrointestinal (GI) side effects after injections, and 77% experienced treatment-related injection site reactions (ISRs). " 01/01/2020 - "Five localised and self-limiting injection site reactions were identified in 3 horses out of 98 injections (5.1%). "
3.	Intranasal Administration 01/01/2004 - "Although the efficacy of intranasal agents varies with the product used, intranasal delivery may be both convenient and more effective than other modes of drug delivery for a variety of reasons: (i) intranasal administration bypasses small bowel gastrointestinal tract absorption, which is often significantly delayed during the acute phase of a migraine attack; (ii) nauseated patients may prefer non-oral formulations as they decrease the chance of vomiting and are more rapidly effective; (iii) intranasal administration causes no pain or injection site reaction and is easier and more convenient to administer than injection or suppository and so may be used earlier in a migraine attack, resulting in better efficacy; (iv) intranasal medication produces the same number or fewer adverse events than injections; and (v) intranasal formulations offer a more rapid onset of action than oral medications, for some of the above reasons and, as such, may be more useful in patients with cluster headache, although this needs to be verified. "
4.	Subcutaneous Injections 07/01/2023 - "Injection site reactions following subcutaneous injection of biologic agents is not well described in the literature. " 11/01/2017 - "Injection-site reactions were more common with subcutaneous injections (5.7% versus 0%, respectively). " 08/01/2016 - "This prospective study evaluated the frequency and type of injection site reactions when the maximum subcutaneous injection volume was increased from 2 to 3 ml per injection site. " 10/01/1995 - "With the subcutaneous injection, injection site reactions occur in approximately 30%. " 02/01/2010 - "Subcutaneous injections may be associated with local injection site reactions (LISRs), which can include itching, pain, swelling, or redness. "
5.	Intravenous Administration 09/01/2013 - "Patients who received at least 1 dose each of subcutaneous and intravenous administration were surveyed regarding preference, satisfaction, injection site reactions, and quality of life measures. " 08/01/2001 - "After intravenous administration, the main adverse events are injection site reaction and flu-like syndrome. " 07/01/2019 - "Updated report on incidence of infusion-site reactions associated with peripheral intravenous administration of fosaprepitant." 06/01/2014 - "Incidence of infusion-site reactions associated with peripheral intravenous administration of fosaprepitant." 01/01/2021 - "This study aimed to compare the incidence of infusion site reactions (ISRs) induced by intravenous administration of brand-name and generic vinorelbine (VNR) for treating non-small cell lung cancer. "