Cross-sensitivity Entries

Cross-sensitivity Overview

The term "cross-sensitivity" refers to an increased likelihood of a patient experiencing an allergic reaction to a given drug or drug allergy category based on a pre-existing allergy to a separate drug or category. Each cross-sensitivity entry provides information on known associations between drugs/categories that result in an increased risk of allergic reactions.

Mechanisms underlying the existence of cross-sensitivity are varied and not fully understood. The majority of cross-sensitivities can be understood through similar structural features between drugs/drug classes. For example, the β-lactam antibiotics possess similar groupings of side chains (R1/R2 groups), which are the best predictors of cross-sensitivity, even among members of different β-lactam classes.

In some cases, the cross-sensitive agents require transformation to a common product or set of products, either through metabolic reactions or exposure to specific environmental triggers. For example, quinine and quinidine are not normally cross-sensitive. However, they pose a risk of cross-sensitive reactions in patients when exposed to sunlight.

Finally, in other cases, the mechanism underlying cross-sensitivity is not predictable based on chemical structure and needs to be further studied. For example, cross-sensitivity has been described between diltiazem and verapamil, two structurally unrelated calcium channel blockers, though the mechanism is not currently known.

A given pair of drugs may show up in multiple cross-sensitivity entries. This most often occurs when a drug is part of a category that has category-level cross-sensitivity entries. For example, clarithromycin belongs to the macrolide antibiotic category. Due to this, it has the potential to be cross-sensitive with other macrolides and tacrolimus. However, specific cross-sensitivity information for clarithromycin with azithromycin and erythromycin (both macrolides) also exist based on specific case reports.

Notably, although the underlying mechanisms remain uncertain, all cross-sensitivity entries are based on documented real-world clinical or theoretical evidence. Given that the rate of cross-sensitivities vary greatly and are influenced by individual patient characteristics, it is impossible to document every possibility. However, every drug/category in our dataset has been investigated for known cross-sensitivities in the literature. Therefore, the lack of a cross-sensitivity entry between two drugs/categories means that we did not find evidence for this reaction in the literature. The lack of an entry does not mean a patient will not experience cross-sensitivity between drugs.

Cross-sensitivity Incidence

The incidence field provides a representation of the reported cross-sensitivity rate. As information regarding the exact rate is not available for all drug/category combinations, it is impossible to provide a single value. However, we limit possible values to the following:

  • At least X%
  • Up to X%
  • X%
  • X-Y%
  • Common
  • Uncommon
  • Rare
  • Single case reports
  • Theoretical (cross-sensitivity is possible based on in vitro results or other evidence)

Cross-sensitivity Evidence Type

The evidence_type field returns a list of tags indicating the kinds of sources that the provided information is from. These are the same as for allergy detail evidence types.

Cross-sensitivity Description

The description field returns a concise (1-2 paragraph) overview of clinical/theoretical evidence supporting the possibility of cross-sensitivity between two drugs. This field's content varies depending on the understanding of the cross-sensitivity based on information available in the literature. In general, the description discusses the incidence of the cross-sensitivity, which includes specific details from case reports and other resources. If the underlying mechanism is hypothesized or known, it is mentioned. Finally, if general guidelines for the management or avoidance of cross-sensitive reactions are outlined in the literature, they are also included.

Cross-sensitivity Structure Overview

    "drug": {
"name": "Acetaminophen", "drugbank_id": "DB00316"
"summary": "Acetaminophen is known to be cross-sensitive with NSAIDs (Salicylates)"
"description": "While acetaminophen is considered a tolerable drug in patients with sensitivity to several non-steroidal anti-inflammatory drugs (NSAIDs),[T803] cross-sensitivity between aspirin and acetaminophen in aspirin-sensitive asthmatic patients has previously been reported with frequencies ranging from 0% to 29%. In one prospective study, there was no cross-sensitivity demonstrated between aspirin and acetaminophen in non-aspirin-sensitive asthmatic patients. In contrast, about 34% of aspirin-sensitive asthmatic patients reacted to high-doses (1000 to 1500 mg) of acetaminophen. Most reactions were limited to bronchospasm and unspecified nose and eye reactions.[A222814]"
"incidence": "Up to 34%"
, "evidence_type": [
], "cross_sensitive_drugs": [ {
"name": "Acetylsalicylic acid", "drugbank_id": "DB00945"
}, {
"name": "Balsalazide", "drugbank_id": "DB01014"
}, {
"name": "Benorilate", "drugbank_id": "DB13657"
}, {
"name": "Carbaspirin calcium", "drugbank_id": "DB13612"
This is a response to a cross-sensitivity API call for an acetaminophen product concept. This structure tells us that acetaminophen (DB00316) is known to be cross-sensitive with NSAIDs (Saliscylates)with an incidence rate up to 34%. Prior allergic reactions to other drugs such as Acetylsalicylic acid (DB00945), Balsalazide (DB01014), Benorilate (DB13657), Carbaspirin calcium (DB13612), and other NSAIDs can increase the likelihood of an allergic reaction to acetaminophen; the reverse is also true. The evidence supporting this comes from an uncontrolled trial. For more details you can take a look at the description, where you will find additional information like a short summary of the research that has shown this cross-sensitivity.