This presentation aims to provide education on adverse drug reactions (ADR) to hospital staff.

1. Mazdak Zamani
SHPA VIC Branch
October 2012
Melbourne Australia
Are you allergic to any
medication?

2. Objectives
Learn about Common
ADR & Medicines Prevention
ALLERGY involved & Treatment
The best approach to ‘Adverse Drug Reactions’ is to prevent them

3. 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 ADRs
Background
Stevens-Johnson Syndrome
Angioedema
Severe Rash
Anaphylaxis
References 6, 10, 11

4. 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 reactions
References 1, 6, 10

5. 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
metoclopramide
References 1, 6, 9, 10

6. 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 patients
References 1, 6, 9, 10

7. Overview
Allergy Types

8. 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

9. References 10

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 animals
References 1, 4, 10

11. 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

12. 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 Cephalexin
References 4, 5, 10

13. 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 cautiously
References 4, 5, 10

14. β-Lactam Antibiotcs
Penicillins Cephalosporins Carbapenems
Generic Brand Generic Brand Generic Brand
Amoxil, Curam,
Amoxycillin Cefaclor Ceclor Doripenem Doribax
Augmentin
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
Bicillin L-A Ceftriaxone Rocephin
penicillin
Benzylpenicillin BenPen Cefuroxime Zinnat
Phenoxymethyl
Abbocillin Cephalexin Keflex, Rancef
penicillin
Procaine
Cilicaine Cephazolin Kefzol
penicillin

15. 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 meds
References 1, 2, 8

16. 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

17. 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
reactions
References 1, 9, 10

18. 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 iodine
References 1, 9, 10

19.  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
Chemotherapy
References 1, 10

20.  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
Chemotherapy
References 1, 10

21. 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 attacks
References 6, 7

22. 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 ADR
References 1, 10

23. Prevention and Treatment
The best approach to ‘Adverse Drug Reactions’ is to prevent them

24. 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 exists
References 4, 9, 10

25. Educate Patients
and provide ADR Alert cards

26. 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 Corticosteroids
References 4, 10

27. Local Policies
Alert Documentation
Medication Prescribing
Medication Administration
Anaphylaxis
Desensitisation
Latex Allergy
References

28. 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 drugs
References 1, 10

29. ? Case Scenarios
Let see who has been listening!

30. 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 closely
1
B. Suggest ceasing ceftriaxone immediately and change
to moxifloxacin due to β-lactam hypersensitivity
Case
C. Document that patient ‘well-tolerated’ ceftriaxone and
continue the treatment

31. 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 EN
2
D. Sulfur 2% Cream
Case
E. Frusemide
F. Sodium Sulfite (preservative
221)

32. 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 observed
3
C. Suggest ceasing flucloxacillin and
prescribing lincomycin
Case

33. References
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.

34. Summary
We cause more harm to our patients
by not looking or listening
than not knowing!
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35. Thank you…
Questions?
Image from http://www.pharmainfo.net/cartoons/patient-allergy-information