Allergy to penicillin

– PRE-PEN® (benzylpenicilloyl polylysine injection USP) is the only FDA-approved diagnostic skin test for the evaluation of penicillin allergyi,ii – BEDMINSTER, N.J., Jan. 4, 2024 /PRNewswire/ -- The Danish, pharmaceutical company ALK (ALKB:DC / OMX: ALK B / AKBLF), today announced it has successfully completed its acquisition of the business assets of AllerQuest, a U.S.-based company dedicated to manufacturing PRE-PEN® (benzylpenicilloyl polylysine injection USP) Skin Antigen Test. This acquisition makes ALK the sole manufacturer and distributor of PRE-PEN in the U.S. and Canada, with global ownership rights to all assets of AllerQuest. PRE-PEN is the only FDA-approved diagnostic skin test for the evaluation of penicillin allergy and is indicated for the assessment of sensitization to penicillin (benzylpenicillin or penicillin G) in patients suspected to have clinical penicillin hypersensitivity.i,ii (Please see Important Safety Information below.) Hans Lindeberg, senior vice president of ALK in North America, says: "This transaction reaffirms ALK's commitment to penicillin allergy testing and antimicrobial stewardship as well as supporting action plans, including that of the World Health Organization (WHO), in response to the growing threat of antibiotic resistance and infectious diseases. We are proud to ensure continued delivery of quality products and services to healthcare providers and their patients to ultimately help improve outcomes for those who might be affected by a penicillin allergy, and we thank AllerQuest for trusting us on this matter." In the U.S., 10% of people report that they have a penicillin allergy yet, according to the Centers for Disease Control and Prevention (CDC), less than 1% of the population is actually allergic.iii,iv Correctly identifying patients who are not allergic to penicillin can help them receive first-line antibiotic therapy recommended by guidelines, and decrease exposure to broad-spectrum antibiotics, which can reduce incidence of adverse events and antibiotic resistance.v Antibiotic resistance is a growing concern worldwide, with the CDC estimating that more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, and more than 35,000 resulting deaths.vi By ensuring continued availability of skin antigen tests for penicillin, and through its deep allergy expertise, ALK aims to be part of the solution to help address this public health concern. James Wolfe, M.D., President of AllerQuest says: "We are proud of our partnership with ALK for over 14 years to distribute PRE-PEN in the U.S. and Canada. ALK is well-positioned to assume manufacturing capabilities for PRE-PEN and will continue to provide this important test to the millions of patients who are labelled as penicillin allergic." ALK expects the acquisition to strengthen its American business, but it will not have a material financial impact on the company's financial results for 2024. For further information, please contact ALK Headquarters in Denmark (CET): Investor Relations: Per Plotnikof, tel. +45 4574 7527, mobile +45 2261 2525 Media: Maiken Riise Andersen, tel. +45 5054 1434 About PRE-PEN PRE-PEN is indicated for the assessment of sensitization to penicillin (benzylpenicillin or penicillin G) in patients suspected to have clinical penicillin hypersensitivity. A negative skin test to PRE-PEN is associated with an incidence of immediate allergic reactions of less than 5% after the administration of therapeutic penicillin, whereas the incidence may be more than 50% in a history-positive patient with a positive skin test to PRE-PEN. These allergic reactions are predominantly dermatologic. Whether a negative skin test to PRE-PEN predicts a lower risk of anaphylaxis is not established. Similarly, when deciding the risk of proposed penicillin treatment, there are not enough data at present to permit relative weighing in individual cases of a history of clinical penicillin hypersensitivity as compared to positive skin tests to PRE-PEN and/or minor penicillin determinants. About ALK ALK is a global specialty pharmaceutical company focused on allergy and allergic asthma. It markets allergy immunotherapy treatments and other products and services for people with allergy and allergy doctors. Headquartered in Hørsholm, Denmark, ALK employs around 2,700 people worldwide and is listed on Nasdaq Copenhagen. Find more information at IMPORTANT SAFETY INFORMATION The risk of sensitization to repeated skin testing with PRE-PEN is not established. Rarely, a systemic allergic reaction including anaphylaxis (see below) may follow a skin test with PRE-PEN. To decrease the risk of a systemic allergic reaction, puncture skin testing should be performed first. Intradermal skin testing should be performed only if the puncture test is entirely negative. PRE-PEN is contraindicated in those patients who have exhibited either a systemic or marked local reaction to its previous administration. Patients known to be extremely hypersensitive to penicillin should not be skin tested. No reagent, test, or combination of tests will completely assure that a reaction to penicillin therapy will not occur. The value of the PRE-PEN skin test alone as a means of assessing the risk of administering therapeutic penicillin (when penicillin is the preferred drug of choice) in the following situations is not established: Adult patients who give no history of clinical penicillin hypersensitivity. Pediatric patients. In addition, the clinical value of PRE-PEN where exposure to penicillin is suspected as a cause of a current drug reaction or in patients who are undergoing routine allergy evaluation is not known. Likewise, the clinical value of PRE-PEN skin tests alone in determining the risk of administering semisynthetic penicillins (phenoxymethylpenicillin, ampicillin, carbenicillin, dicloxacillin, methicillin, nafcillin, oxacillin, amoxicillin), cephalosporin-derived antibiotics, and penem antibiotics is not known. In addition to the results of the PRE-PEN skin test, the decision to administer or not administer penicillin should take into account individual patient factors. Healthcare professionals should keep in mind the following: A serious allergic reaction to therapeutic penicillin may occur in a patient with a negative skin test to PRE-PEN. It is possible for a patient to have an anaphylactic reaction to therapeutic penicillin in the presence of a negative PRE-PEN skin test and a negative history of clinical penicillin hypersensitivity. If penicillin is the drug of choice for a life-threatening infection, successful desensitization with therapeutic penicillin may be possible irrespective of a positive skin test and/or a positive history of clinical penicillin hypersensitivity. Occasionally, patients may develop an intense local inflammatory response at the skin test site. Rarely, patients will develop a systemic allergic reaction, manifested by generalized erythema, pruritus, angioedema, urticaria, dyspnea, hypotension, and anaphylaxis. The usual methods of treating a skin test antigen-induced reaction—the applications of a venous occlusion tourniquet proximal to the skin test site and administration of epinephrine—are recommended. The patient should be kept under observation for several hours. Pregnancy Category C: Animal reproduction studies have not been conducted with PRE-PEN. It is not known whether PRE-PEN can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. The hazards of skin testing in such patients should be weighed against the hazard of penicillin therapy without skin testing. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. Please see full Prescribing Information for additional Important Safety Information. References ____________________________ i Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. US Food and Drug Administration. Accessed December 2023. . ii PRE-PEN. Prescribing information. ALK-Abelló, Inc.;2013. iii Evaluation and diagnosis of penicillin allergy for healthcare professionals. Centers for Disease Control and Prevention. Updated October 31, 2017. Accessed December 2023. . iv U.S. and world population clock. Accessed December 2023. . v Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183-198. doi:10.1016/S0140-6736(18)32218-9. vi About U.S. Antibiotic Awareness Week (USAAW). Centers for Disease Control. Accessed December 2023. . SOURCE ALK, INC.

TUESDAY, July 25, 2023 -- For patients with low-risk penicillin allergy, direct oral penicillin challenge is noninferior to standard-of-care skin testing followed by oral challenge, according to a study published online July 17 in JAMA Internal Medicine . Ana Maria Copaescu, M.D., from the Centre for Antibiotic Allergy and Research at Austin Health in Heidelberg, Australia, and colleagues examined whether a direct oral penicillin challenge is noninferior to the standard-of-care penicillin skin testing followed by oral challenge in an international randomized clinical trial. A total of 377 patients with a low-risk penicillin allergy were randomly assigned to direct oral challenge with penicillin (intervention arm; 187 patients) or standard-of-care penicillin skin testing (190 patients). Most of the patients had a PEN-FAST score of 0 or 1. The researchers found that the primary outcome of physician-verified positive immune-mediated oral penicillin challenge within one-hour postintervention occurred in 0.5 and 0.5 percent of patients in the intervention and control groups, respectively, with a risk difference of 0.0084 percentage points (90 percent confidence interval, −1.22 to 1.24 percentage points). The one-sided 95 percent confidence interval was below the noninferiority margin of 5 percentage points. Nine immune-mediated adverse events were recorded in the intervention group and 10 were recorded in the control group in the five days following the oral penicillin challenge (risk difference, −0.45 percentage points; 95 percent confidence interval, −4.87 to 3.96 percentage points). There were no serious adverse events reported. "Compared with skin testing, a direct oral penicillin challenge is less resource and time intensive, is less expensive, and has the potential to be performed outside of the specialist allergy setting, providing a scalable approach to address low-risk, unverified penicillin allergy in diverse treatment settings internationally," the authors write. Two authors disclosed ties to the biopharmaceutical and medical technology industries. Abstract/Full Text (subscription or payment may be required) Posted July 2023

Many low-risk patients with a penicillin allergy were able to have their penicillin allergy label removed through a simple procedure known as 'direct oral challenge' as part of a world-first multicenter randomized control trial known as the Penicillin Allergy Clinical Decision Rule (PALACE) study. Penicillin allergy affects more than 25 million people in the United States (up to 1 in 10 Americans) and has been shown to lead to particularly poor health outcomes in pregnant women and surgical patients. It is also a public health threat, leading to antibiotic resistance and infections in hospitalized patients that can be life threatening. Seventy-five% or more penicillin allergy labels come on by age 3 due to, for example, confusion with a viral rash. The majority of these rashes were never allergic, but the labels 'stick' into adulthood and carry many adverse consequences." Many low-risk patients with a penicillin allergy were able to have their penicillin allergy label removed through a simple procedure known as "direct oral challenge" as part of a world-first multicenter randomized control trial known as the Penicillin Allergy Clinical Decision Rule (PALACE) study. In the PALACE study, investigators randomized low-risk penicillin allergic patients to two different approaches to remove their allergy label. They either underwent the current standard of care to have skin testing followed if negative by oral challenge with a penicillin or they went straight to oral challenge ("direct oral challenge") without preceding skin testing. "The majority of patients labeled as penicillin allergic, more than 90%, have low-risk histories, meaning they did not have a history to suggest a severe or more recent reaction to a penicillin," said PALACE study protocol member and Vanderbilt University Medical Center principal investigator Elizabeth Phillips, MD, the John Oates Professor of Clinical Research. "We would expect more than 95% of these patients to have negative testing and be able to take penicillin in the future." The study, undertaken by a team of researchers from specialized centers in North America and Australia, enrolled 382 adults who were assessed using a specialized risk assessment tool called PEN-FAST. Participants were randomly assigned to receive either a direct oral penicillin challenge or the standard approach (penicillin skin testing followed by an oral challenge). The primary goal was to determine if the direct oral penicillin challenge was no worse than the standard method of skin testing followed by oral challenge which needs to be performed in an allergist's office. Only one patient (0.5%) in each group experienced a positive reaction to the penicillin challenge, demonstrating that the direct oral penicillin challenge performs just as well as the standard method. Importantly, there were no significant differences in adverse events between the two groups, and no serious adverse events were reported. The findings have wide-ranging implications for patients. By accurately identifying low-risk penicillin allergy patients, health care providers can ensure appropriate antibiotic prescriptions. Patients with a documented penicillin allergy are more likely to be prescribed alternative antibiotics, known as second-line antibiotics, which are often not as effective against certain infections and may have more side effects. "Patients with penicillin allergy are more likely to get second-line or broader spectrum antibiotics that lead to risk of antibiotic resistance and serious infections such as antibiotic-associated diarrhea due to Clostridioides difficile, which can spread through hospitals and become a major public health problem." Phillips said. "In the U.S. increasingly we also have a major problem with other antibiotic-resistant 'superbugs' such as multi-resistant gram-negative infections, Candida auris and even a resurgence of syphilis for which penicillin is the best treatment and the only treatment that should be used in pregnancy to prevent transmission to an unborn child. "The evidence provided by the PALACE study will change clinical practice. Many patients in the United States do not have direct access to an allergist to provide specialized testing such as skin testing. Therefore, the ability to go to direct oral challenge with a penicillin in low-risk patients which can be carried out in any observed setting will make it easier for patients in the United States to access health care to safely and effectively remove the label of penicillin allergy," she said. The PALACE study was led by Ana-Maria Copaescu, MD, PhD, McGill University Health Centre, Montréal, and senior author Jason Trubiano. PhD, Center for Antibiotic Allergy and Research, Department of Infectious Diseases at Austin Health. Cosby Stone, MD, assistant professor of Medicine in the Division of Allergy, Pulmonology, and Critical Care Medicine, was a co-investigator for VUMC.