If a reaction is happening now
If this might be anaphylaxis, use epinephrine if it has been prescribed and call 911. Follow the written emergency plan if there is one. Guidelines agree that prompt epinephrine injected into the muscle of the mid-outer thigh comes first, with calling for help.E2Good3
What is anaphylaxis?
The World Allergy Organization describes anaphylaxis as the most severe presentation of an acute, whole-body allergic reaction.E2Good1
International guidelines agree on the clinical features that point to anaphylaxis: a life-threatening, generalized allergic or hypersensitivity reaction.E2Good3
In children with peanut or tree nut reactions, 89% of reactions involved the skin (hives, swelling). The airway was involved in 52% (wheezing, throat tightness, repeated coughing, trouble breathing) and the gut in 32% (vomiting, diarrhea).E2Good7
In infants and toddlers, symptoms can look different from those in older children and adults. Age does not predict how severe a reaction will be.E2Good8
The Zyrtec Hives label warns that some symptoms may be signs of anaphylactic shock. These can appear when hives first appear or up to a few hours later.Official text4
Why does every guideline put epinephrine first?
The World Allergy Organization calls intramuscular epinephrine the first-line treatment for anaphylaxis. It notes that epinephrine is still used less often than it should be.E2Good1
International guidelines agree on prompt epinephrine injected into the muscle of the mid-outer thigh. They also agree on lying the person down (or semi-reclining if they are short of breath or vomiting) and calling for help.E2Good3
The EpiPen label explains how epinephrine works. Through alpha receptors it reduces the blood vessel widening and leaking that can drop blood pressure. Through beta receptors it relaxes the airways and helps relieve wheezing and breathlessness.Official text9
US practice parameters state that epinephrine is the first-line drug for both single-phase and two-phase (biphasic) anaphylaxis. They also state that people should be observed until symptoms fully resolve.E2Good10
What do studies of fatal reactions show?
In a study of children with fatal and near-fatal food reactions, the six who died had symptoms within 3 to 30 minutes. Only two of them received epinephrine in the first hour. All who survived received it, all but one within 30 minutes.E2Good5
The authors concluded that failing to recognize how severe a reaction is, and to give epinephrine promptly, increases the risk of death.E2Good5
In a UK study of fatal reactions, all fatal food reactions caused breathing difficulty. The median time to arrest after food was 30 minutes, and epinephrine was given before arrest in only 14%.E2Good6
In a US series of food fatalities, all but one person was known to have asthma, and most did not have epinephrine available. Peanuts and tree nuts caused more than 90% of those deaths.E2Good11
A review found that upright posture is a feature of fatal anaphylaxis, and that delayed epinephrine is a risk factor.Review12
Death from food anaphylaxis is rare. Among people with food allergy, a pooled analysis estimated 1.81 deaths per million person-years, rarer than accidental death in the general population.E1Strong13
Antihistamines, steroids and second reactions
International guidelines agree that H1 and H2 antihistamines and steroids are not the first medicines of choice.E2Good3
A Cochrane review looking for trials of antihistamines in anaphylaxis found no studies that met its criteria, and could make no recommendation for practice.E1Strong14
The over-the-counter Zyrtec Hives label carries this warning, quoted as written:
Not a Substitute for Epinephrine. If your doctor has prescribed an epinephrine injector for "anaphylaxis" or severe allergy symptoms that could occur with your hives, never use this product as a substitute for the epinephrine injector.
Severe anaphylaxis, or needing more than one dose of epinephrine, are risk factors for a second (biphasic) reaction. Antihistamines and steroids are not reliable ways to prevent one.E2Good10
The 2023 US practice parameter adds that when epinephrine is used promptly and the response is prompt, complete and lasting, immediate emergency services may not be required. Counseling on when to call 911 is part of prescribing.E2Good8
What the epinephrine device labels say
The EpiPen label lists emergency treatment of allergic reactions, including anaphylaxis, to stinging and biting insects, allergen immunotherapy, foods, drugs, diagnostic substances and other allergens. It also lists idiopathic and exercise-induced anaphylaxis.Official text9
The EpiPen label says to inject into the front and outer side of the thigh. The injection goes into the muscle or under the skin, through clothing if necessary. The label says never to inject into a vein, the buttocks, fingers, hands or feet.Official text9
The Auvi-Q label covers adults and children who weigh 7.5 kg or more. It recommends that patients have immediate access to two devices at all times.Official text15
Neffy is an epinephrine nasal spray for adults and children who weigh 15 kg or more. Its label says that if it is frozen and needed in an emergency, do not wait for it to thaw; seek emergency care right away.Official text16
The Auvi-Q and neffy labels address symptoms that do not improve or get worse. In that case, they say a second dose may be given with a second device starting 5 minutes after the first. The EpiPen label says more than two doses in a row should be given only under direct medical supervision.Official text9,15,16
The labels' own weight tables follow, shown whole and word for word. They are reference text, not a choice of dose for anyone.
| Weight on the label | Device and dose on the label |
|---|---|
| Patients greater than or equal to 30 kg (approximately 66 pounds or more) | EpiPen 0.3 mg |
| Patients 15 kg to 30 kg (33 pounds to 66 pounds) | EpiPen Jr 0.15 mg |
The label's table, shown whole and word for word. The prescriber or pharmacist chooses the device and dose for each person.
| Weight on the label | Device and dose on the label |
|---|---|
| 30 kg or greater | AUVI-Q 0.3 mg |
| 15 kg to less than 30 kg | AUVI-Q 0.15 mg |
| 7.5 kg to less than 15 kg | AUVI-Q 0.1 mg |
The label's table, shown whole and word for word. The prescriber or pharmacist chooses the device and dose for each person.
| Weight on the label | Spray and dose on the label |
|---|---|
| 30 kg or Greater | One spray of neffy 2 mg |
| 15 kg to less than 30 kg | One spray of neffy 1 mg |
The label's table, shown whole and word for word. The prescriber or pharmacist chooses the device and dose for each person.
| Weight on the label | Dose on the label |
|---|---|
| 30 kg or greater | 0.3 mg |
| 15 kg to less than 30 kg | 0.15 mg |
The label's table, shown whole and word for word. The prescriber or pharmacist chooses the device and dose for each person.
The doses from that auto-injector are fixed. For this reason, its label says other forms of injectable epinephrine are used if a dose lower than 0.15 mg is needed.Official text17
Things that can make a reaction more likely
Exercise, alcohol, anti-inflammatory painkillers (NSAIDs) and infections are well-documented cofactors: they lower the amount of allergen needed to trigger anaphylaxis. Registries find a cofactor in about 30% of anaphylactic reactions.Review18
In wheat-dependent exercise-induced anaphylaxis, reactions happen only when a cofactor is present.Review18
Plans, training and follow-up
For people at risk in the community, international guidelines recommend carrying epinephrine auto-injectors and a written emergency action plan made for the person. They also recommend follow-up with a physician, ideally an allergy specialist.E2Good3
US practice parameters say good prescribing requires counseling and training for patients and caregivers. This includes when and how to use the device and whether and when to call 911.E2Good8
European guidelines recommend structured, comprehensive training for people at risk.E2Good2
After anaphylaxis, the World Allergy Organization advises referral to a specialist to look for the cause and to learn prevention and self-management.E2Good1
What is not known yet
Antihistamines remain widely used as an add-on. But no trials met the Cochrane review's criteria, so their role in anaphylaxis has not been tested properly.E1Strong14
Questions you might bring to your clinician
- Is there a written anaphylaxis action plan, and does it match the device prescribed?
- Which device fits, and how many should be on hand at all times?
- What is the plan for a second dose, and when to call 911?
- Are there cofactors, such as exercise or NSAIDs, worth knowing about in this case?
- Should a tryptase level or a referral to an allergist be part of the follow-up?