Product information and disease description Place of product in therapy Approaches to treatment

Heterogeneity of treatment effect

10 evidence topics · 5 sources

Children and adolescents: pharmacokinetic data limited to participants weighing more than 30 kg

“today announced positive topline results from its pediatric study for Anaphylm™ (epinephrine) sublingual film in patients aged seven to seventeen and weighing greater than thirty kilograms with a personal history of allergic reactions.” (opens the source at this quote in a new tab)
“The pediatric study was a multi-site, single treatment study designed to evaluate the PK, pharmacodynamics (PD), safety, and tolerability of Anaphylm. A total of thirty-two patients completed the study. The PK results were consistent with previous adult studies.” (opens the source at this quote in a new tab)

Infants and toddlers: dose and device uncertainty below 15 kg

“Thus, the actual necessary and sufficient mg/kg dose is unknown, though the 0.01 mg/kg recommendation seems to be at least anecdotally supported by evidence of efficacy.” (opens the source at this quote in a new tab)
“Lack of data to determine whether needle length of available 0.1 mg and 0.15 mg autoinjectors provides more optimal intramuscular delivery of epinephrine.” (opens the source at this quote in a new tab)

High body weight: route of delivery and bioavailability of injected epinephrine

“Overweight women were more likely to experience subcutaneous injection (n = 10 of 12) compared with non-overweight men (n = 1 of 18).” (opens the source at this quote in a new tab)
“However, when the researchers evaluated the bioavailability of epinephrine after an injection, the initial plasma peak was similar in both groups, and the overall bioavailability of epinephrine was higher in the overweight women.” (opens the source at this quote in a new tab)
“There is emerging evidence that the pharmacokinetics of epinephrine may vary between individual patients and between different devices and methods used for administration.” (opens the source at this quote in a new tab)

Oral allergy syndrome and oropharyngeal involvement

“Pollen-food allergy syndrome (PFAS) is another important factor in food-induced anaphylaxis. Although PFAS usually causes mild symptoms limited to the mouth and throat, it can sometimes lead to severe systemic reactions, including anaphylaxis.” (opens the source at this quote in a new tab)

Administration after food exposure

“Its absorption and effectiveness are not notably reduced when taken immediately after eating, which supports its practical use for managing food-related anaphylaxis.” (opens the source at this quote in a new tab)

Concomitant beta-blockers: reduced responsiveness to epinephrine

“Some patients may not respond well to standard doses of adrenaline. Beta-blockers are the most common reason of adrenaline resistance, as they block beta-adrenergic receptors. In these cases, glucagon should be considered because it works independently of these receptors. ACE inhibitors, angiotensin receptor blockers, tricyclic antidepressants, preexisting cardiovascular disease, and older age can also decrease responsiveness to adrenaline.” (opens the source at this quote in a new tab)

Concomitant beta-blockers and angiotensin-converting enzyme inhibitors: severity of reactions

“In both human and mouse models, BBs and ACEIs have been found to increase the severity of anaphylaxis and may have an additive effect when used in combination (which has become a common therapeutic approach in severe CVD).” (opens the source at this quote in a new tab)
“These medications are associated with an increased relative risk that any anaphylactic reaction will be more severe, although the absolute risk of severe anaphylaxis remains small and the risk of stopping or changing the medications may be greater than the risk of continuing them during any planned treatment or procedure.” (opens the source at this quote in a new tab)

Pregnancy: treatment should not be delayed

“Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.” (opens the source at this quote in a new tab)
“During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. Treatment of anaphylaxis during pregnancy should not be delayed.” (opens the source at this quote in a new tab)

Pregnancy: positioning during an episode

“if pregnant, position the patient in a semi-recumbent position on the left side; if unconscious, place in the recovery position.” (opens the source at this quote in a new tab)

Older adults and cardiovascular comorbidity

“Retrospective cohort studies suggest that the risk of adverse cardiac events after epinephrine use is higher in older patients (age ≥50 years).” (opens the source at this quote in a new tab)
“However, those same populations have increased risk of severe or fatal anaphylaxis.” (opens the source at this quote in a new tab)