ABSTRACT
Because reactions to intravenous infusions of radiocontrast media, monoclonal antibodies, or chemotherapy agents can be severe and life-threatening, researchers have tried to decrease their rate and severity by giving antihistamines, corticosteroids, or both before the infusions. This review summarizes the information about corticosteroid pretreatment to prevent infusion-related reactions, to help clinicians determine which patients may benefit from it.
Rates of infusion-related reactions vary by medication class and the individual medication, and so do the data and recommendations about corticosteroid pretreatment, necessitating a medication- and patient-specific approach.
For radiocontrast media, it remains reasonable to consider pretreatment in patients with a history of high-grade reactions, multiple comorbidities, or other factors associated with elevated risk.
For monoclonal antibodies, it may be reasonable to give corticosteroids before the first infusion of agents associated with high rates of reactions (ie, cetuximab, trastuzumab, rituximab, and infliximab). Less evidence supports giving them before subsequent doses of these agents (except for rituximab given for B-cell malignancy) or before monoclonal antibodies with low rates of reactions.
For chemotherapy, corticosteroids are recommended before infusions of taxanes but not platinum or pegaspargase.
Giving corticosteroids beforehand can decrease the risk of reactions to infusions of some medications, while for others it does nothing—and for many drugs we don’t have enough evidence to say.
Here, we examine the evidence and recommendations regarding corticosteroid pretreatment before infusions of 3 of the main offending classes of agents: radiographic contrast media, monoclonal antibodies, and cancer chemotherapeutic drugs.
MANY MECHANISMS, SYMPTOMS
Infusion-related reaction is a broadly encompassing term. Medications differ in molecular structure, and so do reactions to them. Reactions can be nonimmune or immune, the latter mediated by immunoglobulin (Ig) E, or not. Furthermore, they can be either immediate or delayed.
Hypersensitivity reactions are a subset of infusion-related reactions that occur at doses that most patients tolerate and that have objectively reproducible signs or symptoms. Examples include IgE-mediated allergy, IgG- or IgM-mediated reactions such as hemolytic reactions, immune complex diseases such as serum sickness, and delayed T-cell–mediated reactions such as severe cutaneous adverse reactions.1
Corticosteroid pretreatment is primarily indicated for non-IgE–mediated hypersensitivity reactions, a subset of immediate nonimmune-mediated reactions. Even in this subset, mechanisms can vary, and thus response to pretreatment regimens varies as well.
Infusion-related reactions present with a wide range of symptoms: mucocutaneous findings such as pruritus, urticaria, and flushing occur in up to 90% of cases; respiratory manifestations such as wheezing and dyspnea in 40%; and circulatory manifestations such as hypotension in 30% to 35%.2 Neurologic or psychiatric symptoms include dizziness, headache, weakness, syncope, or “sense of impending doom”; gastrointestinal symptoms include nausea, vomiting, or diarrhea; and other symptoms include fever and chills.
While the incidence of hypersensitivity reactions varies with the drug and method of administration, it is often highest with the first dose.
Before they get their first infusion, patients need to be informed about the risk of these reactions. If a reaction does occur and it is mild, initial measures include pausing the infusion and restarting it at a lower rate, giving antihistaminergic drugs, or if appropriate, running the infusion with more fluids. Severe reactions such as anaphylaxis are treated with intramuscular epinephrine, supportive measures, and avoiding the causal agent in the future.
Because infusion-related reactions are common and potentially serious, premedication regimens with corticosteroids, antipyretics, and antihistamines have been studied and implemented, with varying success. These agents aim to mitigate infusion reactions by inhibiting the release of leukotrienes, prostaglandins, cytokines, and histamine.
CORTICOSTEROIDS HAVE BEEN USED A LONG TIME
Corticosteroids were first used in the 1940s, initially for their anti-inflammatory effects in managing rheumatoid arthritis.2 Side effects of chronic and high-dose steroid use were quickly identified and include bone necrosis, osteoporotic fractures, hyperglycemia, hypertension, infections, poor wound healing, and edema.
The 1980s saw corticosteroids beginning to be used to try to prevent infusion-related reactions, specifically reactions to contrast media for angiography, urography, and computed tomography.3–5
PREVENTING REACTIONS TO CONTRAST MEDIA
In the past, when high-osmolality iodinated contrast media were used, 2% to 8% of patients had reactions,6 but the risk is lower with the newer low-osmolality media used for radiographic studies and with gadolinium contrast used for magnetic resonance imaging.7
Guidelines have changed
In 2020, the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the American College of Allergy, Asthma, and Immunology (ACAAI)8 recommended against routinely giving glucocorticoids or antihistamines to prevent anaphylaxis in patients who had previously had hypersensitivity reactions to radiocontrast media if they needed to have another infusion of a low- or iso-osmolar, nonionic contrast agent. This was a conditional recommendation, and the level of evidence was rated as very low.
In 2025, however, the AAAAI and the American College of Radiology (ACR)9 recommended premedication for patients with a history of severe reactions to radiocontrast media who cannot undergo an alternative imaging study and for whom the untoward consequences of premedication and delayed diagnosis are small. They did not recommend premedication for patients with a history of mild reaction. They mentioned that the direct risks of corticosteroid premedication are generally minor. Again, the level of evidence was low.
Evidence base
Several early trials of giving corticosteroids to prevent contrast infusion reactions compared high-, iso-, and low-osmolality iodinated contrast media. The high-osmolality agents have a reported adverse event rate 4 to 10 times higher than the event rates of the low- and iso-osmolality agents.10
Two randomized blinded trials3,11 conducted in the 1980s and 1990s are frequently cited as supporting corticosteroid prophylaxis. However, these studies and many others had significant limitations in applicability owing to their design.
Lasser et al,3 in 1987, performed a trial in 6,763 patients who were about to receive high-osmolality contrast media, dividing them into 3 groups: 1 group received methylprednisolone 12 hours before and again 2 hours before the infusion, 1 group received only a single dose of methylprednisolone 2 hours before the infusion, and 1 group received placebo. Compared with the placebo group, the 2-dose group (but not the 1-dose group) had significantly fewer reactions overall (6.4% vs 9.0%, P < .0001), fewer reactions that necessitated therapy (1.2% vs 2.2%, P = .008), and fewer grade 3 reactions (ie, shock, bronchospasm, laryngospasm, loss of consciousness, convulsions, hypotension, arrhythmia, angina, angioedema, or pulmonary edema [0.2% vs 0.7%, P = .04]).
Lasser et al,11 in 1994, performed another randomized trial, this one in 3 institutions with more than 1,000 participants receiving low-osmolality contrast media, who received either oral methylprednisolone 6 to 24 hours before and again 2 hours before the contrast infusion, or placebo. The methylprednisolone group had a significantly lower incidence of overall reactions (1.7% vs 4.7%, P = .005) and mild reactions (0.2% vs 1.9%, P = .004). They also had fewer moderate and severe reactions, but the differences were not statistically significant.
These 2 trials played a pivotal part in establishing the role of giving corticosteroids before contrast media. However, both studies are limited in applicability, as they did not specifically investigate patients who had previously had reactions to radiocontrast media.
The 2020 recommendation against giving corticosteroids and antihistamines8 was based on 6 observational studies10,12–16 of patients who had previously had reactions to radiocontrast media, whereas the 2 trials by Lasser et al3,11 did not have the prior-reaction criterion. Analysis of these 6 studies demonstrated a trend toward increased risk in patients who got premedication, with a risk ratio of 1.07, which failed to reach statistical significance (95% confidence interval 0.67–1.71). Also, there was significant heterogeneity across studies (P < .001, I2 = 93%).8
Overall, counting both medication recipients and nonrecipients, 1,741 (8.6%) of the 20,128 patients in these studies had reactions. Some of the patients received the same radiocontrast media the second time around, but others got different ones.8 Three of the studies12,15,16 found lower rates of reactions when radiocontrast media were switched, but this topic is beyond the scope of this review.
Overall, we lack high-quality data regarding corticosteroid pretreatment in patients with prior reactions to radiocontrast media. The limited data we do have indicate that pretreatment does not decrease the risk with subsequent exposure. However, given the current paucity of evidence, pretreating patients at higher risk (eg, those with a history of high-grade reactions, multiple comorbidities, or considered at high risk for other reasons) seems reasonable, and is our current practice, in line with the 2025 consensus statement.9
PREVENTING REACTIONS TO MONOCLONAL ANTIBODIES
Monoclonal antibodies are key components of cancer and rheumatologic therapy. However, these nonendogenous proteins can elicit multiple reactions, including antidrug antibody formation leading to allergic reactions. Chimeric and murine monoclonal antibodies are more immunogenic than fully humanized ones.17
Infusion-related reactions to monoclonal antibodies occur most frequently with the initial dose, with rates that vary greatly depending on the agent: as high as 77% with the first infusion of rituximab to as low as 0% to 4% with panitumumab.18–20
The number of monoclonal antibodies approved for clinical use has been growing rapidly: as of 2022, 162 had been approved by at least 1 regulatory agency in the world and 122 had been approved in the United States.21 With different mechanisms of actions and rates of reactions, it is not feasible to comment on all these medications. Therefore, here we focus on those with the highest rates of reactions: cetuximab, trastuzumab, rituximab, and infliximab.
Cetuximab
A retrospective study published in 2015 assessed the efficacy of intravenous corticosteroids and histamine 2 blockers in decreasing the risk of infusion reactions in 243 patients receiving cetuximab for squamous cell carcinoma of the head and neck. High-grade reactions occurred in 11 (5.1%) of the 216 patients who received corticosteroids (hydrocortisone or dexamethasone) 1 hour before infusion, compared with 5 (19%) of the 27 patients who did not (P = .023).22
Similarly, a post-hoc analysis of the MABEL (Monoclonal Antibody Erbitux in a European Pre-License) study,23 published in 2010, found a lower overall rate of infusion-related reactions in patients with metastatic colon cancer who received corticosteroids plus antihistamines (9.6%) than in those who received antihistamines alone (25.6%). The trend was similar for grade 3 or 4 reactions (1% vs 4.7%), but it did not reach statistical significance.
There are little data regarding pretreatment with corticosteroids after an initial infusion-related reaction, as rechallenging patients after grade 3 or 4 reactions is not recommended.
Trastuzumab
A retrospective study published in 2023 involved 176 patients who collectively received 2,320 infusions of trastuzumab for breast cancer management.24 The rate of infusion-related reactions was significantly lower in patients who received dexamethasone before the infusion than in those who did not (odds ratio 0.61 for each 1 mg of dexamethasone given, 95% confidence interval 0.43–0.85, P = .003). As with cetuximab, most of these reactions (91.4%) occurred with the first dose.
A 2014 study in 197 patients with breast cancer had similar results when corticosteroids were given before the loading dose of trastuzumab: the rates of infusion-related reactions were 10% vs 19% (P = .065).25 In this study, 32 of the 33 patients who experienced a reaction to trastuzumab were rechallenged. Of these, 20 (63%) received premedication, and only 1 of the 32 patients, who did not receive pretreatment, had a subsequent infusion-related reaction.25
Rituximab
Data on corticosteroid pretreatment for rituximab are complicated by the use of this monoclonal antibody for both rheumatologic and oncologic diseases, as the risk of reactions seems higher when it is given to patients with cancer.
Jung et al26 and Ding et al27 both found significantly lower rates of infusion-related reactions to rituximab given for B-cell malignancies with corticosteroid pretreatment. Jung et al26 retrospectively found that corticosteroids reduced the rate from 41.2% to 8.3% (P = .017) with first infusions. Ding et al27 performed a randomized trial of a novel prednisone premedication protocol with a modified rituximab, cyclophosphamide, epirubicin, vincristine, and prednisone (R-CHOP)–like regimen for each infusion, which reduced the total incidence of infusion reactions in the first cycle from 43.2% to 15.9% (P = .0051) and the second cycle from 27.3% to 6.8% (P = .0107).
Infliximab
Rates of infusion reactions to infliximab varied widely in different studies, ranging from 5% to 23%.28 A comprehensive literature review in 2019 evaluating 10 studies in 3,892 patients found that giving corticosteroids and antihistamines before infliximab infusions did not decrease the risk of acute hypersensitivity reactions.29
The 2020 AAAAI/ACAAI anaphylaxis practice parameters8 included an analysis of 4 studies that evaluated giving corticosteroids before infliximab. This analysis demonstrated no significant benefit from pretreatment, with a relative risk of 1.58 favoring no premedication (95% CI 0.87–2.87).
As more and more monoclonal antibodies get approved, clinicians will need to be aware of rates of infusion-related reactions in clinical trials and any ongoing research evaluating pretreatment regimens for these specific medications. For example, amivantamab received US Food and Drug Administration approval in September 2024 and was noted to have an infusion-related reaction rate of 67%.30 Within a year, Spira et al31 reported that in 40 patients who received dexamethasone 8 mg as pretreatment, infusion reactions occurred in 9 (22.5%).
Based on available data, it seems reasonable to give corticosteroids before the first infusion of monoclonal antibodies that are associated with a high rate of reactions. However, there is less evidence to support corticosteroid pretreatment for monoclonal antibodies with low rates of reactions, or for pretreatment beyond the first dose of high-risk monoclonal antibodies, except for continued corticosteroid pretreatment for rituximab given for B-cell malignancy.
PREVENTING REACTIONS TO CHEMOTHERAPEUTIC AGENTS
Several chemotherapy agents, including pegaspargase, paclitaxel, carboplatin, cisplatin, procarbazine, and anthracyclines, are associated with increased risk of infusion-related reactions, which can result in avoidance or use of a less-effective agent. Because many agents are approved and in use, we will discuss the ones most studied in relation to infusion-related reactions.
The incidence of infusion-related reactions varies greatly among the chemotherapeutic agents, with reported rates of 12% for carboplatin, 0.5% to 25% for oxaliplatin, 21% for docetaxel, and 2% to 45% for paclitaxel.32
Prophylactic corticosteroids, specifically dexamethasone, are currently recommended for patients receiving paclitaxel, docetaxel, cabazitaxel, and procarbazine. In fact, the standard of care for taxane administration includes corticosteroid pretreatment.33,34 The dosing and duration of prophylaxis often varies with the infusion agent.
AlMuhizi et al,35 in 2020, reviewed 73 studies of premedication strategies to reduce the incidence of reactions to the first infusion of chemotherapeutic agents and found that most premedication regimens were derived empirically rather than through randomized trials. Nevertheless, they concluded that the evidence indicates that premedication with corticosteroids, antihistamines, histamine 2 antagonists, and leukotriene receptor antagonists significantly reduces the incidence and severity of infusion-related reactions to chemotherapy agents.
Pegaspargase
Studies have not found corticosteroid pretreatment to reduce the incidence of reactions to pegaspargase.36,37
Paclitaxel
A retrospective cohort study, published in 2002, compared 2 protocols for prophylactic corticosteroids before paclitaxel treatment: 2 doses of oral corticosteroids vs a single dose of intravenous corticosteroid. The rate of hypersensitivity reactions was significantly lower in the 107 patients who received 2 oral doses than in the 110 patients who got a single intravenous dose (7.5% vs 17.3%, P = .047).34
Multiple studies found that the rate of reactions did not increase if corticosteroid pretreatment was stopped after the first 2 infusions of paclitaxel.38–40 A retrospective study in 2014 revealed that 75% of patients with paclitaxel infusion-related reactions underwent rechallenge, and 91% of them tolerated rechallenge without corticosteroid pretreatment.41 Interestingly, 5 of the patients who were rechallenged had an initial infusion-related reaction classified as severe by the Brown classification, and 4 of the 5 tolerated rechallenge.41
Platinum agents
Platinum agents, unlike most other medications, cause more reactions with subsequent exposures. For example, the rate of carboplatin hypersensitivity reactions increases from 1% in the first 6 cycles to 27% after 7 doses.42 The reason for the increase with exposure is that these reactions are due to IgE-mediated allergy, which requires sensitization through previous exposure before a reaction can occur.42 In view of the IgE-mediated mechanisms, skin testing protocols as well as desensitization protocols exist for platinum chemotherapeutics, which have become the standard of care for these medications and allow for continued use after initial hypersensitivity reactions.42
CORTICOSTEROIDS…FOR SOME
Certain medications and classes of medications are prone to cause infusion-related reactions, which may be severe and life-threatening. Efforts to minimize the rates of these reactions have included slowing the infusion rate; premedicating with antihistamines, antipyretics, or corticosteroids; and avoiding agents once they cause problems.
For radiocontrast media, some studies have suggested that premedication with corticosteroids decreases the incidence of infusion-related reactions. However, applicability of the results from these studies is limited, given the study populations. Initial data suggested that corticosteroid premedication before an infusion of radiocontrast media may decrease the likelihood and severity of infusion-related reactions. However, the population assessed in these studies was not limited to those who previously had a reaction to radiocontrast media. A subsequent meta-analysis found no change in reaction rates in patients with a history of prior reactions to radiocontrast media undergoing subsequent exposure to radiocontrast media with corticosteroid pretreatment.8 These data have led to conflicting recommendations between the 2020 AAAAI/ACAAI anaphylaxis practice parameters8 and the 2025 consensus statement from the AAAAI and ACR.9
Some monoclonal antibodies cause more reactions than others. Studies involving cetuximab, trastuzumab, and infliximab have shown lower rates of infusion-related reactions with corticosteroid pretreatment for the loading dose, though data are limited for subsequent doses. Data for rituximab suggest continued benefit for corticosteroid pretreatment with subsequent infusions.26,27 Overall, based on current data, pretreatment with corticosteroids for initial infusions of monoclonal antibodies with high rates of infusion-related reactions is reasonable, though there are less data to support pretreatment for subsequent infusions, except for rituximab.
Chemotherapy agents have been associated with high risk of infusion-related reactions depending on the class of medication. Some classes have stronger recommendations for corticosteroid premedication, given their higher incidences of reactions. Taxanes such as docetaxel, cabazitaxel, and paclitaxel have current recommendations for premedication with corticosteroids before infusion, thanks to studies demonstrating a decreased rate of reactions with premedication. However, steroid premedication is not routinely performed nor recommended before platinum infusions. For pegaspargase, multiple studies did not show a decrease in the incidence of reactions. Overall, pretreatment recommendations vary among chemotherapeutic classes due to the differing benefits in rates of reduction of risk.
CONCLUSION
Rates of infusion-related reactions vary depending on medication classes. Corticosteroid premedication is well established for some medications, has been shown to not be beneficial for other medications, and has little data for yet others, necessitating a medication- and patient-specific approach to pretreatment. Further data and research are necessary to expand recommendations regarding the utility of corticosteroid prophylaxis before infusions.
DISCLOSURES
Dr. Fernandez has disclosed teaching and speaking for Baxalta. The other authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
- Copyright © 2026 The Cleveland Clinic Foundation. All Rights Reserved.
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