Hypersensitivity Reactions and Allergies to Chemotherapy Flashcards
What are the 4 classes of HSR? Describe the clinical manifestations and how they are mediated.
Type I - Immediate
- IgE mediated
- Clinical manifestations: Anaphylaxis, angioedema, urticaria, asthma, food allergies, allergic rhinitis
Type II - Cytotoxic
- IgM and IgG mediated
- Clinical manifestations: Cytopenias, myasthenia gravis, Grave’s disease, blood transfusion reactions
Type III - immune complex
- IgM, IgG complex mediated
- Clinical manifestations: Serum sickness, vasculitis, rheumatoid arthritis, systemic lupus erythematosus
Type IV - Delayed
- T-lymphocyte mediated
- Clinical manifestations: Contact dermatitis, multiple sclerosis, graft rejection
Compare and contrast infusion reactions vs. allergic reactions.
Infusion Reactions
•Occurs during infusion of the drug
•Clinically similar to Type I, but unlikely to be IgE mediated
•May be direct effect on immune cells leading to a cytokine release syndrome
Symptoms are generally mild in infusion reactions:
•Flushing/redness
•Pruritus, rash
•Back pain, arthralgia
•Symptoms resolve quickly with cessation of infusion or treatment
•Tolerate re-challenge at slower rate of infusion
Allergic Reactions
•Usually immediate, may require repeat exposure
•Usually Type I, IgE mediated
•Release of histamines, leukotrienes, and prostaglandins
Generally more severe reactions with allergies
•Hives/urticaria
•Chest pain/tightness
•SOB, anaphylaxis
•Symptoms do not resolve quickly with cessation of infusion or treatment
•Do not re-challenge, may require desensitization
What are the incidence of infusion reactions with paclitaxel and docetaxel? Incidence of true allergic reactions?
What’s the rationale for these infusion reactions?
What’s the timing of these reactions?
Paclitaxel: Up to 45% due to cremophor
Docetaxel: Up to 21% due to polysorbate 80
Incidence of allergic reactions to taxane moiety: <1%
Onset: 10 - 30 minutes within start of infusion and usually 1st or 2nd infusion
What’s the cross reactivity for paclitaxel and docetaxel infusion reactions? for allergic reactions?
Cross-reactivity
Infusion Reactions: May tolerate docetaxel after reaction to paclitaxel (different diluents)
Allergic reactions: Up to 90% will react to docetaxel after reaction to paclitaxel (taxane moiety)
What pre-medications should be given Paclitazel and Docetaxel for allergic reactions?
Paclitaxel pre-medications
- Dexamethasone 10-20 mg IV
- Diphenhydramine 25-50 mg IV
- Famotidine 20 mg IV
Docetaxel pre-medications
-Dexamethasone 20 mg IV
Platinum reactions
- More likely infusion or allergic?
- Timing?
Primarily allergic HSR
-Incidence is highest at 8+ lifetime cycles
(1st cycle - 1% –> 6th cycle 6.5% –> 8+ cycles -27%)
-Due to exposure to low levels of free platinum metal over time
-Hypersensitivity reaction may occur minutes to weeks after start of the infusion with 50% of reactions being moderate to severe: Type I. Type IV reactions can occur too.
What are risk factors for developing an allergic reaction to platinums?
- Re-introduction of the drug after a period of time of no exposure
- Multiple cycles of drug during the first and subsequent exposures
- IV administration (rather than PO or IP administration)
- Existing hypersensitivity to certain drugs
- Environmental factors
Incidence of infusion reactions and causative agent for
a) liposomal doxorubicin
b) etoposide
c) bevacizumab
Onset & timing of reactions?
Symptoms?
Liposomal Doxorubicin -Up to 10% due to liposome Etoposide -3% due to polysorbate 80 Bevacizumab -3% due to monoclonal antibody
Onset and timing: 10-30 minutes within start of infusion and 1st infusion
Symptoms for all: Flushing, shortness of breath, chest pain
How do you manage infusion reactions with Liposomal doxorubicin, etoposide, and bevacizumab?
Liposomal doxorubicin
- Pre-medication optional: Dexamethasone 10-20 mg IV
- PI: Infuse over 1 hour
- MDACC GYN: 1st infusion over 3 hours, subsequent over 1 hour (if tolerated)
Etoposide
- Pre-medication optional: Dexamethasone 10-20 mg IV
- PI: Infuse over at least 30 min to prevent hypotension
- MDACC GYN: Infuse over 2 hours
Bevacizumab
- Pre-medications: None
- PI: 1stinfusion over 90 min, 2nd over 60 min, subsequent over 30 min
- MDACC GYN: ALL infusions over 30 min
What’s the acute management of HSR as a nurse?
- STOP INFUSION
- Assess airway, breathing, circulation, and orientation immediately
- If patient is unresponsive at any point, call a code
- Monitor vital signs every 5 minutes
- Activate Hypersensitivity Algorithm
- Page On-Call Physician STAT
What questions do you want to know when nurse calls you about HSR with a patient?
Questions to ask:
- Which chemo was administered?
- How much drug has been infused?
- What cycle of chemotherapy is the patient receiving?
- Severity and resolution of symptoms?
- Were pre-meds given and timed appropriately?
- What has been done?
Mild Reaction
1.May re-challenge at reduced infusion rate (ie. half rate) after resolution of symptoms
Severe Reaction
- Do NOT rechallenge
- Discharge once symptom-free for 30 minutes
Define mild HSR reaction
Define severe HSR reaction
mild reaction: hot flushing, rash, pruritus
severe reaction: anaphylaxis, SOB, BP changes, GI symptoms with nausea/vomiting, hives)
What do you do differently when you see for the subsequent treatment cycles?
What about HSR to paclitaxel or carboplatin?
Pre-medications:
-Add additional or increase doses
Re-challenge
a) Mild reaction
- Re-challenge with prolonged infusion
b) Moderate reaction
- Consider re-challenge with prolonged infusion
- Consider desensitization
c) Severe reaction
- Generally do not re-challenge
- May consider desensitization in select cases
d)Exception: Due to risk for a more severe reaction upon re-challenge, platinum agents typically require desensitization
Hypersensitivity reaction to paclitaxel
-Can administer docetaxel or albumin bound-paclitaxel
Hypersensitivity reaction to carboplatin
-Can administer cisplatin
Standard and extended infusion times for
- paclitaxel
- weekly paclitaxel
- docetaxel
- liposomal doxorubicin
- etoposide
- bevacizumab
Paclitaxel
3 hours vs 6 hours
Weekly paclitaxel
1 hour vs 2-3 hours
Docetaxel
1 hour vs 2-3 hours
Liposomal doxorubicin
1-3 hours vs 3-6 hours
Etoposide
2 hours vs 3-4 hours
Bevacizumab
30 minutes vs 60-90 minutes
Success rate of carboplatin desensitization?
Success rates vary significantly based on the protocol (50-99%)
What’s MDACC desensitization protocol (i.e. carboplatin)?
Home Pre-medications:
- Dexamethasone 20 mg PO on the evening prior to and the morning of chemotherapy desensitization
- ->Patient Education: “Pre-medications for Chemotherapy Hypersensitivity”
- ->In select patients, more extensive pre-medications may be utilized
30 minutes prior to desensitization:
- Dexamethasone 20 mg IV
- Diphenhydramine 50 mg IV
- Famotidine 20 mg IV
4 steps over 4 hours
- 0.1% over 1 hour
- 1% over 1 hour
- 10% over 1 hour
- 89.9% over 1 hour
What do you do in desensitization failure for carboplatin?
Re-challenge depends on severity of reaction and timing
May consider:
A)Increasing home pre-medications:
-Dexamethasone 20 mg PO Q6 hours x 4 doses
-Diphenhydramine 50 mg PO Q6 hours x 4 doses
-Famotidine 20 mg PO Q12 hours x 2 doses
B) Adding additional immediate pre-medications
-Consider giving additional dexamethasone or diphenhydramine immediately prior to the offending bag
C) Consider prolonging infusion
-Only for 3rd (10% of dose) or 4th bags (89.9% of dose)
D) Switching agent
-75% of patients who react to carboplatin may tolerate switching to cisplatin
Describe the management of minor HSR
A)STOP infusion
B)Monitor vitals q5 minutes
C) Symptoms
-If fever/chills/rigors –> acetominophen
-itching, flushing, hives
–> diphenhydramine 50 mg IV.
–> If no improvement in 5 minutes then give hydrocortisone 100 mg IV x 1 and diphenhydramine 50 mg IV x 1.
-If anaphylaxis
–> place O2 monitor
–>administer O2 to get sat >= 92%,
–> start IV fluids (NS @ 150 cc/hr) and consider 2 IVs
–> epi 1:1000 (e.g. 1 mg/ml) in 0.5 ml IM x1 at outer mid-thigh and repeat q5 - 15 minutes if no response
–> Diphenhydramine 50 mg IV x 1
–> Hydrocortisone 100 mg IV x 1
–> nebulized bronchodilators PRN
