Mazdak ZamaniSHPA VIC Branch

October 2012Melbourne Australia

Are you allergic to any medication?

Objectives

The best approach to ‘Adverse Drug Reactions’ is to prevent them

1Learn about ADR &

ALLERGY

2Common

Medicines involved

3Prevention

& Treatment

Back

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ndAdverse 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

ADRs

Angioedema

Stevens-Johnson Syndrome

Anaphylaxis Severe Rash

References 6, 10, 11

ADR- Adverse Drug ReactionsAll unintended pharmacological effects of a

drug except therapeutic failures, intentional over dosage, abuse of the drug or errors in administration1

Predictable • 85% of all ADR• Dose dependent• Related to pharmacologic actions• Caused by Active ingredients• e.g. side effects

Unpredictable• 15% of all ADR• Dose independent• Unrelated to pharmacologic actions• Active ingredients or excipients• e.g. allergic reactions

References 1, 6, 10

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 metoclopramide

Predictable ADR

References 1, 6, 9, 10

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 patients

Un-predictable ADR

References 1, 6, 9, 10

Allergy Types

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Immediate reactions - Within 1(-2) hours, mainly IgE mediated (usually type 1 allergy); e.g. urticaria, angioedema, bronchospasm and anaphylaxis

Delayed reactions - After 1(-2) hours (often > 6hrs up to 6 weeks), mainly T-cell mediated (usually type 4 allergy); e.g. Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN) and Drug reaction with eosinophilia and systemic symptoms (DRESS)

Allergy Sub-Types

Both immediate (e.g. anaphylaxis)

and delayed reactions (e.g. SJS) may be potentially

life-threatening

References 1, 10

References 10

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 animals

Allergy Risk Factors

References 1, 4, 10

2 Common Medicationswith potential for serious allergy

Drug allergic reactions have been reported to almost all medications, however certain drugs are more frequently associated with specific types of reactions

• Antibiotics• Aspirin and NSAIDs• Opiates• Anticonvulsants• ACE Inhibitors

• Radio Contrast Media• Chemotherapeutic Agents• Preoperative Agents• Complementary Medicine• DMARDs

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

β-Lactam Antibiotcs

Penicillin Core Structure Beta-Lactam Core Cephalexin

References 4, 5, 10

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 cautiously

β-Lactam Antibiotcs

References 4, 5, 10

β-Lactam AntibiotcsPenicillins Cephalosporins Carbapenems

Generic Brand Generic Brand Generic Brand

Amoxycillin Amoxil, Curam, Augmentin Cefaclor Ceclor Doripenem Doribax

Ampicillin Ampicyn Cefalotin Keflin Ertapenem Invanz

Flucloxacillin Flopen, Staphylex Cefepime Maxipime Imipenem Primaxin

Dicloxacillin Diclocil Cefotaxime Cefotaxime Meropenem Merrem

Piperacillin Tazocin, Tazopip Cefoxitin Cefoxitin

Ticarcillin Timentin Ceftazidime Fortum

Benzathine penicillin Bicillin L-A Ceftriaxone Rocephin

Benzylpenicillin BenPen Cefuroxime Zinnat

Phenoxymethylpenicillin Abbocillin Cephalexin Keflex, Rancef

Procaine penicillin Cilicaine Cephazolin Kefzol

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 meds

Sulfonamide Antibiotics

References 1, 2, 8

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)

Sulfonamide Antibiotics

References 1, 2, 8

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 reactions

Radiocontrast Agents

References 1, 9, 10

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 iodine

Radiocontrast Agents

References 1, 9, 10

Chemotherapy

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

References 1, 10

Chemotherapy

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

References 1, 10

• 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 attacks

Complementary Medicine

References 6, 7

Always document and compare the generic names of the medications vs ADR

Cross Reactivity

References 1, 10

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.

3 Prevention and Treatment

The best approach to ‘Adverse Drug Reactions’ is to prevent them

A. A thorough history is essential:1. What is the name of the medication?2. What were the reactions?3. How severe were the reactions?4. How long ago did this occur?5. Have you tried similar medicines?

B. Check the generic names of the prescribed medicines against the known ADR thoroughly

C. Avoid the offending agents and those with the high risk of cross reactivity if severe hypersensitivity exists

PREVENTION

There is generally no way to prevent development of a drug allergy. However, we can prevent

the recurrence of known ADR.

References 4, 9, 10

PREVENTION

Educate Patientsand provide ADR Alert cards

» Discontinue the medication when possible » Mild to moderate reactions:

o Antihistamineso Corticosteroids

» Resuscitation in serious reactions» Anaphylactic reactions:

o Adrenalineo Oxygeno Inhaled β agonisto IV Fluidso BP supporto Antihistamineso Corticosteroids

TREATMENT

References 4, 10

Alert DocumentationMedication PrescribingMedication AdministrationAnaphylaxisDesensitisationLatex Allergy

Local Policies

References

Desensitization is contraindicated in

patients with severe delayed reactions such

as Stevens-Johnson Syndrome and TEN

• Temporary induction of drug tolerance to a drug they are allergic to when there are no reasonable alternatives

• Anaphylaxis is not a contraindication

• Two types: – Rapid desensitization in immediate

hypersensitivity e.g. penicillin– Slow desensitization in delayed

hypersensitivity e.g. TB drugs

Desensitization

After desensitization, patient still considered allergic to the medication

References 1, 10

? Case Scenarios

Let see who has been listening!

Case

1 A. Suggest prescribing hydrocortisone to prevent anaphylaxis and observe the patient closely

B. Suggest ceasing ceftriaxone immediately and change to moxifloxacin due to β-lactam hypersensitivity

C. Document that patient ‘well-tolerated’ ceftriaxone and continue the treatment

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?

Case

2

A. Morphine SulfateB. Selenium SulfideC. Pyralin END. Sulfur 2% CreamE. FrusemideF. Sodium Sulfite (preservative

221)

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”?

Case

3

A. Suggest ceasing flucloxacillin and changing to cephazolin

B. Suggest continuing flucloxacillin as no reaction has been observed

C. Suggest ceasing flucloxacillin and prescribing lincomycin

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?

1. 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.

References

Summary

We cause more harm to our patients by not looking or listening

than not knowing!

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Questions?

Thank you…