Immediate reactions - Within 1(-2) hours, mainly IgE mediated; silent sensitization; initially well tolerated; quick development of symptoms at re-exposure; e.g. urticaria, angioedema, bronchospasm and anaphylaxis Delayed reactions - After 1(-2) hours (often > 6hrs up to 6 weeks), mainly T cell and occasionally IgG mediated; Cytotoxic mechanisms are always involved; sensitisation and symptoms often at 8-10th day of therapy; e.g. Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN) and Drug reaction with eosinophilia and systemic symptoms (DRESS)
Because penicillin-related compounds are produced by the cephalosporiummold, early cephalosporin antibiotics contained trace amounts of penicillin. Thus, penicillin contamination may have led early studies of allergy to cephalosporins and penicillin to overestimate the degree of cross-reactivity.
Spelling with ‘f’ is approved by TGA not ‘ph’
More examples:Feverfew has aspirin-like activity and may increase the risk of bleeding while taking blood thinners like warfarin or aspirin.Milk thistle and chamomile can interfere with some of the liver enzymes and increase or decrease the effects of some medications.St John’s wort can cause serotonin toxicity in patients on other antidepressants
Alert Documentation PolicyThe admitting Medical Officer or the first Health Care Provider who is made aware of an allergy or adverse drug reaction is responsible for documenting in HealthSMART CS and on Medication Chart. If the patient is not known to have allergies then ‘No Known Allergies’ (NKA) must be recordedMedication Prescribing PolicyAll drug allergies and/or adverse drug reactions must be documented and verified in HealthSMART CS on the medication chart, patient medical record, clinical alert sheet by the admitting prescriber or other Healthcare Professionals associated with the patient’s care Medication Administration PolicyCheck for patient sensitivities and allergies (i.e. from patient, alerts sheet, ID band, treatment sheet, admission notes or other sources)
C is correct
C is correct
A is correct
Are you allergic to any medication?
Mazdak Zamani SHPA VIC Branch October 2012 Melbourne AustraliaAre you allergic to anymedication?
Objectives Learn about Common ADR & Medicines Prevention ALLERGY involved & Treatment The best approach to ‘Adverse Drug Reactions’ is to prevent them
Adverse Drug Reactions Very common and can occur in 10-15% of courses of drug therapy Account for 3-6% of all hospital admissions Mostly occur due to non-immunological or unknown mechanisms Allergic or immunological mechanisms accounting for 5-10% of all ADRsBackground Stevens-Johnson Syndrome Angioedema Severe Rash Anaphylaxis References 6, 10, 11
ADR- Adverse Drug Reactions All unintended pharmacological effects of a drug except therapeutic failures, intentional over dosage, abuse of the drug or errors in administration Predictable Unpredictable • 85% of all ADR • 15% of all ADR • Dose dependent • Dose independent • Related to pharmacologic actions • Unrelated to pharmacologic actions • Caused by Active ingredients • Active ingredients or excipients • e.g. side effects • e.g. allergic reactionsReferences 1, 6, 10
Predictable ADR Pharmacological side effects - known adverse effects of a pharmaceutical e.g. constipation caused by opiate analgesics Drug-drug interactions - known interactions of a pharmaceutical e.g. tramadol induced serotonin toxicity in patients under treatment with antidepressants Drug-disease/patient interactions - known contraindications of a pharmaceutical e.g. worsening of Parkinson’s disease induced by metoclopramideReferences 1, 6, 9, 10
Un-predictable ADR Drug allergy - an immunologically mediated response to a pharmaceutical or excipient agent in a sensitised person e.g. urticaria or anaphylaxis to penicillins Pseudoallergy - a reaction that mimics an allergy but is caused by non–IgE mediated release of histamine e.g. NSAID/Aspirin induced asthma and bronchospasm Drug intolerance (sensitivity) - an undesirable pharmacologic effect that may occur at low or usual doses of the drug e.g. low dose morphine/codeine induced hallucination Drug idiosyncrasy - a non-immunological reaction that has an unknown mechanism and may be due to underlying genetic or acquired abnormalities of metabolism, excretion, or bioavailability e.g. haemolytic anaemia induced by sulfa meds in G6PD patientsReferences 1, 6, 9, 10
Allergy Sub-Types Immediate reactions - Within 1(-2) hours, mainly IgE mediated (usually type 1 allergy); e.g. urticaria, angioedema, bronchospasm and anaphylaxis Both immediate Delayed reactions - After 1(-2) hours (e.g. anaphylaxis) (often > 6hrs up to 6 weeks), mainly and delayed T-cell mediated (usually type 4 reactions (e.g. SJS) allergy); e.g. Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN) and may be potentially Drug reaction with eosinophilia and systemic life-threatening symptoms (DRESS)References 1, 10
Allergy Risk Factors Drug related factors • Nature of the drug • Degree of exposure - dose, duration, frequency and repeated administration • Route of administration - e.g. allergic reactions to penicillins occur more frequently following parenteral rather than oral administration • Cross Sensitisation - Reactivity either to drugs with a close structural chemical relationship or to immunochemically similar metabolites Host related factors • Age - ages between 20 and 49 at higher risk of allergic reactions • Sex - slightly more common in women • Genetic factors • Concurrent medical illness - asthma, EBV or HIV infection, etc • Previous exposure - e.g. via meat from antibiotic fed animalsReferences 1, 4, 10
Common Medications with potential for serious allergy • Antibiotics • Radio Contrast Media • Aspirin and NSAIDs • Chemotherapeutic Agents • Opiates • Preoperative Agents • Anticonvulsants • Complementary Medicine • ACE Inhibitors • DMARDs Drug allergic reactions have been reported to almost all medications,however certain drugs are more frequently associated with specific types of reactions
β-Lactam Antibiotcs Penicillin Allergy is the most prevalent medication allergy 10% of all patients claim to be penicillin allergic but 9 out of 10 are often able to tolerate penicillin Most common true reactions are urticaria, pruritis and angioedema Possible cross reaction may occur with other β-lactam antibiotics such as cephalosporins and carbapenems Penicillin Core Structure Beta-Lactam Core CephalexinReferences 4, 5, 10
β-Lactam Antibiotcs Cross reactivity is controversial and reported to be between 6-47% Possible 3-11% cross reactivity in those with immediate reactions (type 1 allergy) Penicillin ‘skin allergy testing‘ is recommended before choosing broad spectrum antibiotics Most hypersensitivity reactions to cephalosporins are probably directed at the side chains rather than the core β-lactam So if allergic to cephalosporins, other β-lactam antibiotics can be used cautiouslyReferences 4, 5, 10
Sulfonamide Antibiotics Commonly known as Sulfa Meds Being told that one is allergic to ‘Sulfur’ or ‘Sulphur’ commonly causes confusion Sulfur is an important building block of life Allergy to sulfonamide antibiotics (Sulfa Meds) DOES NOT increase the likelihood of allergy to sulfur powder, sulfite preservatives, sulfate salts (e.g. morphine sulfate) or non-antibiotic sulfonamide medicines Non-antibiotic sulfonamides include frusemide, gliclazide, celecoxib, hydrochlorthiazide, probenecid, etc DO NOT cross react with Sulfa medsReferences 1, 2, 8
Sulfonamide Antibiotics Sulfonamide antibiotics (Sulfa meds): 1. Sulfamethoxazole (Bactrim, Resprim & Septrim) 2. Sulfadiazine (Silvazine cream, Flamazine cream & tablets) 3. Sulfadoxine (for malaria) 4. Sulfacetamide (Bleph-10 eye drop) 5. Sulfapyridine which is part of Sulfasalazine (Pyralin, Salazopyrin) If you have had an allergic reaction to Bactrim there is no way of knowing whether the allergy was to sulfamethoxazole or to trimethoprim, therefore you should avoid trimethoprim (Alprim, Triprim) as well as sulfonamide antibiotics (Sulfa meds)References 1, 2, 8
Radiocontrast Agents Also known as IV Contrast ‘Iodine Allergy’ is misleading! Iodine is an essential trace mineral required for thyroid hormone synthesis Severe allergic reactions occur in 1-3% of patients Older high-osmolar and ionic agents have a greater risk of reactionsReferences 1, 9, 10
Radiocontrast Agents Cross-reactivity between seafood or shellfish and radiocontrast agents is a common misconception (both contain iodine) Shellfish or seafood allergy is related to the proteins found in the meat of the fish NOT iodine Allergy to iodinated antiseptics (Betadine) is due to other parts of the molecule NOT iodineReferences 1, 9, 10
Hypersensitivity reactions have been reported for virtually all commonly used chemotherapeutic agents Reactions range from mild cutaneous eruptions to fatal anaphylaxis Some cases may be due to non-immune mediated release of histamine or cytokines ChemotherapyReferences 1, 10
Most commonly occurs with: – Platinum compounds (cisplatin, carboplatin) – Epipodophyllotoxins (teniposide, etoposide) – Asparaginase – 6-mercaptopurine – Taxanes (paclitaxel) – Procarbazine – Doxorubicin Both cutaneous and systemic allergic reactions have been reported after treatment with mabs ChemotherapyReferences 1, 10
Complementary Medicine • While complementary and alternative medicines are often considered to be safe, adverse drug reactions may occur • Allergic reactions are most common in people with other allergic diseases, such as asthma or allergic rhinitis • Example: – Echinacea is a popular herbal medicine found in some cold and flu remedies. Allergic reactions to Echinacea can be severe including severe urticaria and anaphylaxis, as well as acute asthma attacksReferences 6, 7
Cross Reactivity Avoid Glucosamine and Protmaine in patients allergic to seafood and shellfish. Some vaccines contain traces of egg and some antibiotics such as gentamicin and neomycin. Codeine and Hydromorphone are derivatives of Morphine. Avoid if truly allergic to one. Always document and compare the generic names of the medications vs ADRReferences 1, 10
Prevention and TreatmentThe best approach to ‘Adverse Drug Reactions’ is to prevent them
There is generally no way to prevent development of a drug allergy. However, we can prevent the recurrence of known ADR. A. A thorough history is essential: B. Check the generic names of the 1. What is the name of the medication? prescribed medicines against the 2. What were the reactions? known ADR thoroughly 3. How severe were the reactions? C. Avoid the offending agents and those 4. How long ago did this occur? with the high risk of cross reactivity if 5. Have you tried similar medicines? severe hypersensitivity existsReferences 4, 9, 10
TREATMENT » Discontinue the medication when possible » Mild to moderate reactions: o Antihistamines o Corticosteroids » Resuscitation in serious reactions » Anaphylactic reactions: o Adrenaline o Oxygen o Inhaled β agonist o IV Fluids o BP support o Antihistamines o CorticosteroidsReferences 4, 10
Desensitization Desensitization is contraindicated in • Temporary induction of drug patients with severe tolerance to a drug they are allergic delayed reactions such to when there are no reasonable as Stevens-Johnson alternatives Syndrome and TEN • Anaphylaxis is not a contraindication • Two types: After desensitization, – Rapid desensitization in immediate patient still considered hypersensitivity e.g. penicillin allergic to the medication – Slow desensitization in delayed hypersensitivity e.g. TB drugsReferences 1, 10
? Case Scenarios Let see who has been listening!
Your patient has past history of angioedema to penicillin. She has accidently received one dose of ceftriaxone for urosepsis in emergency department yesterday. She has not experienced any adverse reaction. What is the best advice? A. Suggest prescribing hydrocortisone to prevent anaphylaxis and observe the patient closely1 B. Suggest ceasing ceftriaxone immediately and change to moxifloxacin due to β-lactam hypersensitivityCase C. Document that patient ‘well-tolerated’ ceftriaxone and continue the treatment
Which of the following medications must be avoided in a 33 year old male patient with documented severe skin ADR (Steven’s- Johnson Syndrome) to “Sulfur”? A. Morphine Sulfate B. Selenium Sulfide C. Pyralin EN2 D. Sulfur 2% CreamCase E. Frusemide F. Sodium Sulfite (preservative 221)
Your patient is allergic to penicillin but cannot remember the reaction (happened over 20 years ago). He was given three doses of flucloxacillin for severe cellulitis before you noticed the error. What is the most appropriate intervention? A. Suggest ceasing flucloxacillin and changing to cephazolin B. Suggest continuing flucloxacillin as no reaction has been observed3 C. Suggest ceasing flucloxacillin and prescribing lincomycinCase
References1. Annals of Allergy, Asthma & Immunology. Drug Allergy: An Updated Practice Parameter. October 2010: VOLUME 105.2. William B Smith. Sulfur allergy label is misleading. Aust Prescr 2008; 31: 8–10.3. Constance H Katelaris. Iodine allergy label is misleading. Aust Prescr 2009; 32: 125–8.4. American Academy of Allergy, Asthma and Immunology. Medication and Drug Allergic Reaction: Tips to Remember. 2012.5. The Australasian Society of Clinical Immunology and Allergy (ASCIA) Education Resources. Allergic Reactions to Antibiotics. January 2010.6. The Australasian Society of Clinical Immunology and Allergy (ASCIA) Education Resources. Adverse Drug Reactions. January 2010.7. The Australasian Society of Clinical Immunology and Allergy (ASCIA) Education Resources. Adverse Reactions to Alternative Medicines. January 2010.8. The Australasian Society of Clinical Immunology and Allergy (ASCIA) Education Resources. Sulfonamide Antibiotic Allergy. January 2010.9. Steven Blanner. Drug Allergies and Cross Reactivities. March 2011.10. Werner Pichler, Bernard Thong. Drug Allergy. June 2011.11. The Australasian Society of Clinical Immunology and Allergy (ASCIA) Education Resources. Common Myths About Allergy and Asthma Exposed. January 2010.
SummaryWe cause more harm to our patients by not looking or listening than not knowing! www.slideshare.net
Thank you…Questions? Image from http://www.pharmainfo.net/cartoons/patient-allergy-information