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Drug Allergy

Alice Oborne PhD,

Consultant pharmacist-safe medication practice and MSO

Medicines Use and Safety Network, 6 November 2014

Objectives

• Demographics

• Immediate and delayed reactions

• Allergy questions – Allergy vs ADR

• Documentation

• Written information to patients

• Referrals for allergy testing

• Steps to keep us all safe

– “Stop and check”

Allergy vs adverse drug reaction: definitions

Allergy

• Inappropriate immune-mediated response to a harmless substance

Drug allergy: … immune-mediated reaction to medicinal product

Current draft NICE guideline definition

• …Any reaction caused by a drug with clinical features compatible with an immunological mechanism

Differs from Adverse Drug Reaction:

• An unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal

conditions of use, suspected to be drug related

Page 3Drug allergy: demographics

• Most commonly due to penicillins

• No precise prevalence data

• 10-20% of hospitalised patients report a penicillin allergy

– Of these 1-10% are genuinely allergic

• Penicillin causes 0.7% to 10% of all cases of anaphylaxis

• Risk of anaphylaxis is 0.004% and 0.015% for each course

National data from NRLS, April 12 - March 13

15907Total

12287No Harm

2771Low

828Moderate

14Severe

7Death

Number of reportsDegree of Harm to Patient

With thanks to D Cousins and C Rosario, NHSE

100%15907Grand Total

<1%27Supply or use of over-the-counter medicine

<1%71Advice

1%232

Preparation of medicines in all locations /

dispensing in a pharmacy

2%267Monitoring / follow-up of medicine use

4%647Other

46%7288Administration / supply from a clinical area

46%7375Prescribing

Percentage (%)

Number of

reportsMedication Process

National data 2, Stage of Medication Use Process

77Grand Total

1Incorrect documentation of drug allergy

5No known previous drug allergy

15Unclear if previous unknown allergic reaction

56 (73%)

Drug prescribed/administered even with documented

allergy

Frequency

Did an error occur when the patient had a previous

known allergy?

National data 3, Thematic analysis: allergy known?

77Grand Total

1Antiplatelet

1Metoclopramide

1Alcohol wipes

1Xray contrast

1Antihistamine

1Penicillamine

1Gelofusine

1Plasma substitute

1Anti-epileptic

2Excipient

2Chemotherapy/ Cytotoxic

2Unknown

1Codeine

5Anaesthesia

2NSAID

5Opioid

1Tetracycline

1Trimethoprim

3Cephalosporin

44 (57%)Penicillin

FrequencyTherapeutic Group

National data 4, Thematic analysis: Drug involved

1. Immediate reactions, rapidly evolving: anaphylaxis; urticaria or

angiooedema with hypotension or bronchospasm

2. Non-immediate reactions without systemic involvement

• Acute generalised exanthematous pustulosis or fixed drug eruptions

3. Non-immediate reactions with systemic involvement

• Drug reaction with eosinophilia and systemic symptoms (DRESS)

• Drug hypersensitivity syndrome (DHS)

• Toxic epidermal necrolysis (TEN)

• Stevens-Johnson syndrome (SJS)

4. Common disorders caused rarely by drug allergy

• Eczema, hepatitis, photosensitivity, vasculitis

Practical classification of drug allergy Page 8

• Usually type I hypersensitivity

• Occur quickly after a single dose of drug

• Mast cell degranulation, releasing histamine

• Anaphylaxis

• Urticaria

• Angioedema

• Airway compromise

• Or hypotension

Classification1. Immediate reactions Page 9

Classification2. Non-immediate reactions

• Type IV hypersensitivity

• Can take 6-10 days to develop (earlier with subsequent exposures)

No systemic involvement, lower mortality e.g.

• Rash

• Morbilliform

• Exanthematous

• Maculopapular

Classification: 2. Non-immediate severe: Stevens-Johnson Syndrome

• High mortality

• Desquamation

• Mucosal membrane involvement

• Systemic symptoms

Classification: 2. Non-immediate severe:

Toxic Epidermal Necrolysis (TEN)

• High mortality

• Desquamation

• Mucosal membrane involvement

• Systemic symptoms

Questions to establish allergy or adverse drug reaction

1. What drug(s) is suspected?

2. What was time between ingestion/administration of drug and onset of reaction?

3. Was nature of the reaction in keeping with known adverse reactions to drug?

4. If a rash, what is the nature of the rash?

5. Was there swelling? Where (e.g. facial swelling, lips)?

6. Was there respiratory compromise (difficulty breathing) or in maintaining blood

pressure?

7. Was there any other systematic reaction: liver, renal function abnormalities?

8. Did reaction resolve when the drug was stopped?

9. Responded to antihistamines, steroids?

10.Re-challenge: did reaction recur with re-exposure?

11.Were other drugs administered concurrently that could have caused reaction?

12.Did patient have any underlying condition(s) that could explain reaction?

If in doubt, ask a senior colleague

Allergy vs Adverse drug reaction

• Allergy likely:

• Symptoms of urticaria, angioedema, difficulty in breathing and hypotension occurring within one hour of the last dose of drug

• Non-urticarial rash occurring during a course or within a couple of days of completing a course of the during

• Allergy less likely:

• Symptoms not associated with typical allergic reactions, eg headache, tiredness, migraines etc

• Symptoms are recognised side-effects of the drug, eg bronchoconstriction with beta-blockers, gastritis with NSAIDs, diarrhoea with antibiotics

Use either:

• Drug allergy or

• None known or

• Unable to ascertain

Record, as a minimum:

• Drug name

• Nature of reaction

• Date of reaction

• Ensure visible to all healthcare professionals who use medicines

• Record allergies and ADRs separately

• Check, and update if needed, at every patient contact

• Check before prescribing, supplying, administering

Recording allergy status in healthcare records Page 15

Document new suspected allergic drug reactions in a structured

approach that includes:

• Generic and proprietary drug name

• Description of the reaction

• Indication for which drug was taken

• Date/time of reaction

• Number doses taken or number of days before symptoms onset

• Route

• Drug(s) or classes to avoid in future

Documenting and sharing information with other HCPS

Recording Allergy or ADR: Guys and St Thomas

1. On prescription charts (inpatient, out patient, electronic)

2. All patient records (Electronic patient record, clinical notes, casualty card)

3. Red name band (on same limb as identity band)

4. Communication with other health care professionals (GP, Community Nursing Team)

Check with patient (or carer):

• Before prescribing

• Pharmacy screen / dispensing

• Administration

NICE recommends record allergies and ADRs separately (not currently possible at Guys & St Thomas)

Check and update allergies and confirm with patient (or carers) before

prescribing, dispensing, administering any drug

Ensure that information about drug allergies is included in all

• GP referral letters

• Hospital discharge letters

• Prescriptions issued in any healthcare settings

Implications for

• design of hand-written and electronic discharge letters, and linked e-records

• Handwritten outpatient letters / recommendations to prescribe

• FP10s and linked GP e-records

Maintaining and sharing drug allergy information Page 18

• Discuss suspected allergy with patient (+ parent/ carers)

• Provide written information

• Ensure patient is aware of drug / classes to avoid

• Advise to check with pharmacist before taking OTC medicines

• Record clinician name and date information was given

Information from allergy testing specialist, in writing:

• Diagnosis (allergic or not)

• Drug name and description of reaction

• Investigation performed to confirm/exclude the diagnosis

• Drugs to avoid

• Any safe alternatives

Providing information and support to patients Page 19

General: refer

• Suspected anaphylactic reaction

• Severe non-immediate cutaneous reaction e.g. DRESS, TEN, SJS

Suspected beta lactam antibiotic allergy: refer if

• Needs treatment for disease which can only be treated with beta lactam

• High likelihood of frequent future need for beta lactams e.g. recurrent bacterial

infection or immune deficiency

Suspected NSAID allergy: refer if

• Symptoms such as severe angioedema or asthmatic reactions but needs NSAID

• Asthma with nasal polyps are likely to have NSAID-sensitive asthma

Suspected general anaesthetic allergy: refer if

• Suspected allergic reaction or anaphylaxis during or immediately after GA

Suspected local anaesthetic allergy:

Non-specialist management and referral to specialist services Page 20

Skin testing

• Validated for very few drugs

• Penicillins

• Neuromuscular blocking agents (NMBAs)

• Platinum salts

• Some drugs consistently give false –ve results

• NSAIDs

• Some drugs consistently give false +ve results

• Morphine

• Erythromycin

• NMBAs at high concentration on intradermal testing

NSAID reactions and Selective COX-2 inhibitors

•Advise patient to avoid non-specific NSAIDs including OTC

•May consider selective COX-2 inhibitor if mild reaction to non-specific NSAID if anti-inflammatory is essential

• Discuss with patient first

• Single dose on first day

• Start at low dose

• Only if mild previous reactions

Page 22NICE Guidance on NSAIDs

• After suspected drug-related anaphylactic reaction, take bleed samples for

mast cells tryptase in line with recommendations in Anaphylaxis guideline 134

• Record in notes and on pathology request form the exact timing of samples

• Ensure that tryptase sampling tubes are available in emergency anaphylaxis kits

Serum specific Immunoglobulin E

• Do not use blood IgE for diagnosing drug allergy in non-specialist settings

Measuring serum tryptase after suspected anaphylaxis

Summary

1. New NICE guideline

2. Claimed drug allergy is common, true allergy is rarer but may be fatal

• Not possible to identify which patients have true allergy

3. Classification: Immediate, delayed (mild), delayed (severe)

• Ensure incomplete allergy statements are completed

• Ensure allergies are communicated at transfer

• Document allergies on all prescribing or drug recommendation documents

• NATURE of the reaction and date where known

• Written information to patients on what drugs to avoid

• Refer severe reactions, anaesthetic reactions and beta lactam reactions if likely to need beta lactams in future or if needed now

• Design of e-systems, paper prescriptions, FP10s,

Interventions to help keep patients safe

• Stickers on drug charts (or visible allergy statement in all sections of EPMA)

• Alert on drug cupboards, electronic cabinets “contains penicillin or similar, check allergies”

• - or separate storage if conventions cupboards with advice/warning poster on outside

• Colour coded antibiotic policy

• Drug chart layout (cut away)

• Allergies more visible on ePR and Electronic prescribing (but not yet linked)

• “STOP and check” concept

• Mnemonic for Microbiologist staff giving advice: SAFE: Status and Allergy, Antibiotic–choice, Follow guidelines, don’t use Excessive gentamicin dose

• Colour-coded antimicrobial guidelines (red for penicillins)

• Purchasing: only products with “contains penicillin” on outer packaging

• Pharmacy dispensing label (“contains penicillin”)

• Alert on

• Generic prescribing- increases likelihood of recognising drug is a beta-lactam

• Information – posters, plastic lanyard cards, screensavers,

• Trust Allergy Policy and Procedure

PENICILLIN ALLERGIC Penicillin type drugs include: co-amoxiclav (Augmentin), meropenem, Tazocin