8  Specific Drugs

Antibiotics

Cephalosporins

Background

In the US, 1.3% to 1.7% of the total population reports a cephalosporin allergy whereas 0.5% of pediatric patients report a cephalosporin allergy (Chow, Brunner, and Khan 2024; Khan et al. 2019)

Most reactions to cephalosporins are immediate (74.7%)–characterized by urticaria and/or angioedema–as opposed to delayed–typically non-severe maculopapular exanthem (25.3%).

The chemical structure of cephalosporins is a four membered ring fused with a six membered dihydrothiazine ring with R1 and R2 side chains.

The R1 side chain is the major component responsible for the cross-reactivity with penicillins and cephalosporins. Tolerance to cephalosporins can usually but always be predicted on the basis of similarities or differences in R1 side chains.

R2 side is less studied but may have a role. There is some evidence that suggests that the opening of the cephalosporin beta-lactam ring destroys the R2 side chain.

Trick question! None!

Ceftazadime.

Cefaclor accounts for up to 80% of serum sickness-like reactions.

Figure 8.1: Select cephalosporin cross-reactivity

Skin Testing

Lack of commercial products and metabolites for skin testing.

Immediate Index agents: cephalexin (55.5%), ceftriaxone (24.9%), and cefazolin (17.5%)

8.9% of pateints had positive skin tests (cefazolin 50% positives)

Time since index reaction, OR 0.71 (95% CI 0.57 - 0.90) for positive skin test. (Stone, Trubiano, and Phillips 2021)

Oral Challenge

100% NPV if reaction > 5 years, isolated urticaria, benign MPE, isolated GI symptoms or other non-allergic and orally administere vs 98.5% NPV (95% CI 95.8%-99.7%) if include IV and PO administered. (Stone, Trubiano, and Phillips 2021)

Cephalexin 250 mg oral challenge with 1.5 hour observation. (Koo et al. 2022)

Fluoroquinolones

Macrolides

Background

Macrolides are defined by a large lactone ring, which varies from 12 to 16 carbons, with 1 or more attached sugar chains. Eyrthromycin and clarithromycin have 14 carbons in their lactone rings while azithromycin has 15.

As 50S ribosomal subunit inhibitors, macrolides exert their bacteriostatic effect by inhibiting protein synthesis.

While not extensively studied, macrolide antibiotics with a different number of carbon atoms in their lactone ring are tolerated by most patients. Macrolide antibiotics are also unlikely to cross-react with macrolide immunosuppressants (e.g., tacrolimus, sirolimus).

Clarithyromycin is used as part of combination treatment for H. pylori. Azithromycin is a part of the first-line combination therapy for Mycobacterium avium complex.

  1. GI side effects: Because macrolides are also agonists for the motilin receptor–stimulating gastric and small intestine motility–they can cause nausea, vomiting, diarrhea, and abdmoninal cramping. Accordingly, erythromycin can be used as a treatment for gastroparesis.

  2. Sensorineural ototoxicity (usually transient).

  3. QT interval prolongation.

Skin Testing

Skin testing for macrolide immediate hypersensitivity has not been shown to be reliable.

Oral Challenge

For patients with a history of immediate hypersensitivity reaction to a macrolide, graded azithromycin challenge can be performed, starting with azithromycin 25 mg followed by 1 hour observation then 250 mg followed by 2 hour observation.

For patients with a history of non-severe delayed hypersensitivity reaction to a macrolide, single dose azithromycin 250 mg challenge with 2 hour observation can be performed. Patients should be instructed to report any other delayed symptoms, which may occur up to 24 to 48 hours after the challenge dose.

Penicillins

Background

Approximately 10% of the US population reports an allergy to penicillin.

Less than 5% of these reported penicillin allergies are clinically significant immediate or delayed-immune mediated drug reactions.

Over 95% of patients who do not have a history of serious penicillin allergy are actually tolerant because (1) the most common reported reaction is a benign delayed rash (type IV hypersensitivity reaction) which may or may not recur with subsequent penicillin exposure; (2) IgE-mediated penicillin allergy wanes over time, with 80% of patients becoming tolerant after a decade since their index reaction; and (3) the index reaction may have rather been an intolerance or caused by the underlying infection being treated at the time. (Shenoy et al. 2019)

Individuals who report a penicillin allergy label are more likely to receive broad-spectrum antibiotics that increase the risk for antimicrobial resistance, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. In addition, broad-spectrum antibiotics also increase the risk of developing Clostridium difficile infection.

Receipt of non-beta-lactam perioperative prophylaxis has been associated with an increased risk of surgical site infections.

Epstein-Barr virus. (Chovel-Sella et al. 2013)

About 0.5% to 2.0%

Potentially due to the decrease in use of parenteral penicillins in the outpatient setting, where most antibiotic use occurs.

(Macy et al. 2009)

Skin Testing

The NPV of penicillin skin testing is > 95% when performed with only benzylpenicilloyl polylysine plus penicillin G or with benzylpenicilloyl polylysine plus full panel of minor derterminants.

Reagent Description
Penicilloyl polylysine (PrePen®)

  • Penicilloyl is the Major antigenic determinant (what 95% of penicillin degrades into)

  • PrePen is penicilloyl complexed with polylysine to constitute a multivalent skin test reagent.

  • Polylysine acts like the carrier for the penicilloyl hapten in vivo.
Minor derterminant mixture (MDM)

  • Penicillin G itself, penicilloate, and penilloate

  • Not commercially available expect in South America and Spain
Penicillin G
  • Also called benzylpenicillin
Ampicillin
  • Differs only from penicillin G by the presence of an amino group (-NH2)
Note

Selective IgE-mediated reactions to aminopenicillins are rare in North America (e.g. 3-5% in the United States) versus 25-50% of skin test positive patients in Europe.

Figure 8.2: Penicillin G, ampicillin, and penicilloyl polylysine

The polylysine carrier has ~40 lysine repeats.

Oral Penicillin = Penicillin VK IM/IV Penicillin = Penicillin G Amino group = -NH3

Aminopenicillins = Amoxicillin, Ampicillin Aminocephalosporins = Cephalexin, Cefadroxil, Cefprozil and Cefaclor

References:

Chapter 77 Middleton’s Drug Allergy

Sulfa Antibiotics

Background

The reported global prevalence of sulfa antibiotic allergy is 3% to 6%. The prevalence is higher is individuals with hematological malignancies (12-40%) and HIV (30-70%) (Serrano-Arias et al. 2024).

Sulfa antibiotics–also called sulfonylarylamines–are characterized by the presence of a sulfonamide functional group with two side chains, arylamine (aromatic amine) and an aromatic heterocyclic ring (Serrano-Arias et al. 2024).

No, they do not cross-react because non-antibiotic sulfonamides lack the same side chains as sulfa antibiotics–aryalmine and aromatic heterocyclic ring (Serrano-Arias et al. 2024).

Trimethoprim-sulfamethoxazole is the preferred prophylaxis for Pneumocystis jirovecii pneumonia (PJP) because of its greater evidence of efficacy and lower cost compared to alternative prophylaxis, such as atovaquone, dapsone, and aerosolized pentamidine (Maertens et al. 2016).

Further, compared to alternative PJP prophylaxis, trimethoprim-sulfamethoxazole may also prevent other breakthrough infections such as Nocardia, Toxoplasma, Streptococcus pneumoniae, and Haemophilus species.

A Cochrane review on the efficacy of trimethoprim-sulfamethoxazole for PJP prevention in non-HIV immunocompromised patients found the number needed to treat to prevent one case of PJP is 19 (Stern et al. 2014).

When considering Pneumocystis jirovecii pneumonia prophylaxis, the two main patient populations to consider are non-HIV immunocompromised and HIV immunocompromised individuals.

HIV immunocompromised:

  • CD4+ T cell count < 200 cells/µL

Non-HIV immunocompromised:

  • Solid organ transplant

  • Bone marrow transplant

  • Prednisone ≥ 20 mg (or equivalent) for more than one month

The first cases of Pneumocystis jirovecii pneumonia were described in malnourished children in orphanages in Europe during World War II. When initially described, it was referred to as “interstitial plasma cell pneumonia (Morris et al. 2004).

Pneumocystis jirovecii is a ubiquitous fungus with infection commonly occurring at young age, with near universal positivity to Pneumocystis by two years of age (Vargas et al. 2001). In immunocompetent individuals, primary infection is largely asymptomatic. In addition, colonization with Pneumocystis jirovecii occurs in more than 50% of the general adult population and is assumed to be due to re-infection (i.e. person-to-person transmission, environmental re-exposures) rather than reactivation (Gigliotti and Wright 2012).

DNA sequencing improved our understanding of Pneumocystis and its different species that are associated with various host organisms. Therefore, Pneumocystis jirovecii describes the species that infects humans while Pneumocystis carinii describes the species that infects rats (Stringer et al. 2002).

Hyper-immunoglobulin M syndromes—the X-linked recessive version caused by defects in CD40L (expressed on the surface of T cells to induce antibody isotype switching in B cells)–is associated with a notably increased risk of Pneumocystis jirovecii pneumonia (Davies and Thrasher 2010).

Co-trimoxazole is the British Approved Name (BAN) for trimethoprim-sulfamethoxazole. BANs are assigned for both single-drug and combination preparations. The prefix of “co-” is used for denote combination drugs like trimethoprim and sulfamethoxazole. For example, the combination of amoxicillin and clavulanic acid has the BAN “co-amoxiclav.”

Figure 8.3: Sulfonamides and sulfone structures

Vancomycin

Antiepileptic Drugs

Background

AEDs can be broadly categorized by their structure: aromatic or non-aromatic.

Historically, compounds were labeled as aromatic based on their distinctive aromas.

Today, aromatic compounds and AEDs are defined by containing a benzene ring or other benzene-like properties.

Benzene has a sweet odor and is found naturally (e.g., crude oil) and produced as an intermediate for use in plastics, resins, nylons, synthetic fibers.

2D skeletal representation of benzene

2D skeletal representation of benzene

Aromatic AEDs are associated with the greatest occurence of rash and other cutaneous ADRs, including phenytoin, carbamazepine, phenobarbital, lamotrigine, zonisamide, and oxcarbazapine.

In addition, there is greater cross-reactivity amongst aromatic AEDs (40-58%) than non-aromatic AEDs.

Of the AEDs with lower rash risk, most are non-aromatic (e.g. valproate, gabapentin, levetiracetam, pregabalin, vigabatrin, lacosamide, brivaracetam).

Table 8.1: Select aromatic and non-aromatic AEDs. Adapted from (Mani et al. 2019)
Aromatic AEDs Non-aromatic AEDs

  • Ethosuximide

  • Phenytoin

  • Phenobarbital

  • Carbamepine

  • Oxcarbazepine

  • Zonisamide

  • Lamotrigine

  • Clobazam

  • Felbamate

  • Primidone

  • Eslicarbazepine

  • Perampanel

  • Cannabidiol

  • Valproate

  • Gabapentin

  • Topiramate

  • Levetiracetam

  • Pregabalin

  • Vigabatrin

  • Lacosamide

  • Brivaracetam

  • History of previous AED-related skin reaction

  • Female > Male (2:1), though difference does not persist after > age 50 years

  • Older age

  • Low vitamin D concentrations

Reference

Mani R, Monteleone C, Schalock PC, Truong T, Zhang XB, Wagner ML. Rashes and other hypersensitivity reactions associated with antiepileptic drugs: A review of current literature. Seizure. 2019 Oct;71:270-278. doi: 10.1016/j.seizure.2019.07.015. Epub 2019 Jul 24. PMID: 31491658.

Antihistamines

References

(Shakouri and Bahna 2013)

Buproprion

Gadolinium-Based Contrast Agents

Background

Gadolinium-based contrast agents (GBCAs) are divided into three categories based on their stability and carrier molecule (also called chelating agent): ionic linear, nonionic linear, and nonionic macrocyclic.

GBCAs consist of the combination of the gadolinium ion to its carrier molecule.

The carrier molecule serves to minimize the toxicity of gadolinium in its free form while preserving its contrast properties.

When compared to macrocyclic GBCAs, linear GBCAs have a lower kinetic stability rate, meaning they take a shorter amount for the dissociation of “free” gadolinium.

This is because the macrocyclic form cages the gadolinium ion leading to better protection while the linear form is an open flexible chain with weaker protection.

However, despite their lower stability, linear GBCAs seem to cause less adverse reactions than macrocyclic GBCAs.

Despite their lower stability, linear GBCAs seem to cause less adverse reactions than macrocyclic GBCAs.

Gadolinium is a rare earth element—that does not exist in nature in its pure form due to its high reactivity—and can be extracted from minerals such as monazite and bastnaesite.

When imaging of the hepatobiliary tree is needed, tissue-specific GBCAs (e.g. gadoxetate disodium and gadobenate dimeglumine) are used because they are taken up by hepatocytes and later excreted into the biliary system.

Class Generic Name (Brand Name) Immediate Reactions per 10,000 Administrations
Linear, nonionic Gadodiamide (Omniscan) 1.5
Linear, ionic Gadopentetate (Magnevist), Gadoxetate (Eovist), Gadobenate (MultiHance), Gadofosveset (Ablavar) 8.3
Macrocyclic Gadobutrol (Gadovist), Gadoterate (Dotarem), Gadoteridol (ProHance) 16

References

(Chehabeddine et al. 2019; Behzadi et al. 2018)

Iron

Background

IV iron is used for the treatment of iron deficiency anemia when oral iron is effective or not tolerated.

Formulations available in the United States include low-molecular-weight iron dextran (LWMID), ferric gluconate, iron sucrose, ferumoxytol, iron isomaltoside, and ferric carboxymaltose.

Important

High-molecular weight iron dextrans were discontinued in the United States due to having a higher rate of hypersensitivity reactions.

Table 8.2: Characteristics of iron formulations available in the United States
Generic name Iron gluconate Iron Sucrose LMWID Ferric carboxymaltose Iron isomaltoside Ferumoxytol
Brand name Ferrlecit Venofer INFeD Injectafer Monofer FeraHeme
Molecular weight (kD) 289-440 30-60 165 150 150 750
Labile iron (% injected dose) 3.3 3.5 2 0.6 1 0.8

Immediate Hypersensitivity Reactions

Anaphylactic reactions—when high-molecular weight dextrans are excluded—occur with an incidence of < 1 in 200,000.

Significant differences in reaction risk have not been shown among low-molecular weight iron dextran, iron sucrose, ferric gluconate, and ferric carboxymaltose.

Most IV iron immediate hypersensitivity reactions are mediated through complement-activation related pseudoallergy (CARPA). Rarely, hypersensitivity reactions are IgE-mediated.

Minor Infusion Reactions

Symptoms of minor infusion reactions to IV iron include—flushing, chest/back tightness, myalgias—and, importantly, do not have any features of anaphylaxis.

Labile, or also called “free,” iron is associated with minor infusion reactions to IV iron.

Skin Testing

As most hypersensitivity reactions are non-IgE-mediated—rather via CARPA—skin testing has limited utility for evaluating IV iron hypersensitivity reactions; however, it may help detect the rare patients with IgE-mediated hypersensitivity.

Management

Approaches for patients with history of mild to moderate IV iron reactions include: switching to an alternative IV iron formulation, slowing the infusion rate (e.g., 10% of recommended rate during the first 10 to 15 minutes), and/or pre-treatment with non-sedating, second generation antihistamines.

For patients with a history of anaphylactic reactions to IV iron, desensitization can be considered, such as ferric gluconate.

References

Gómez-Ramírez S, Shander A, Spahn DR, et al. Prevention and management of acute reactions to intravenous iron in surgical patients. Blood Transfusion. Published online April 10, 2019. doi:10.2450/2018.0156-18

Muñoz M, Gómez-Ramírez S, Bhandari S. The safety of available treatment options for iron-deficiency anemia. Expert Opin Drug Saf 2018; 17: 149-59.

Latex

Background

NRL = natural rubber latex > 40,000 products with NRL

Hard rubber latex (heat vulcanized at high temp) Less latex antigen (most allergen denatured at high heat) Medical Consumer Gloves, balloons, condoms

Soft rubber latex (dipping process low heat vulcanization; 10-12% latex products made this way) More latex antigen (less allergen denatured at low heat) Bungs, stoppers Medical Consumer rubber car tires

Skin Testing

Standardized latex for skin testing is not available in the US.

95% Sensitivity (false negative can occur with non-standardized extracts), 100% specificity

Specific IgE Testing

~70-80% sensitivity, 95% specificity

Management

In US, medical devices are required to be labelled with warning if contain NRL.

Latex avoidance if subsequent serologic testing negative; however, negative latex IgE susggestive that inadvertant exposure risk is minimal.

Local Anesthetics

Background

Local anesthetics are divided into two groups: ester and amide.

There is no cross-reactivity between amide and ester LAs.

The most common adverse reaction phenotype associated with LAs are non-allergic, including sympathetic stimulation (pain which can be potentiated by epinephrine if used), systemic toxic effects, and vasovagal syncope.

Amide LAs are used more than ester LAs for several reasons. 1) Amide LAs have longer stability and shelf-life; 2) They are less likely to trigger allergic reactions because unlike ester LAs, they do have a para-aminobenzoic acid (PABA) metabolite which is the main trigger of allergic reactions associated with ester LAs; 3) They are metabolized in the liver whereas ester LAs are broken down by plasma cholinesterase in the blood, leading to variable metabolism and unpredictable pain reduction in individuals and higher potential for systemic toxicity; 4) They have a longer duration of action.

The most commonly used LA is lidocaine, due to its fast onset of action (2 to 5 min), intermediate duration of action (1 to 2 hours), and relatively low potential for systemic toxicity.

For procedures requiring prolonged anesthesia, bupivicaine is often utilized because of its relatively fast onset (5 to 10 minutes) but much longer duration (several hours). Therefore, bupivicaine is used for epidural anesthesia, spinal anesthesia, and peripheral nerve blocks. Of note, bupivicaine has a higher risk of systemic toxicity compared to lidocaine.

Amides Esters

  • Bupivacaine (Marcaine, Sensorcaine)

  • Lidocaine (Xylocaine)

  • Mepivacaine (Carbocaine)

  • Benzocaine (Americaine, Lanacane)

  • Chloroprocaine (Nesacaine)

  • Cocaine

  • Procaine (Novacaine)

  • Tetracaine (Pontocaine)

Skin Testing

LA preparations without epinephrine should be used for skin testing because the vasoconstricting properties of epineprhine may mask a positive test.

Management

If skin testing is negative to lidocaine, a subcutaneous lidocaine 1% with 1.5 mL (15 mg) can be performed followed by a 1.5 hour observation.

Nonsteroidal Anti-Inflammatory Drugs

Background

In the general population, 1.5 - 3.5% of individuals report an NSAID allergy. However, fewer than 20% of those individuals with self-reported NSAID allergy are consistent with a true hypersensitivity.

NSAIDs are important for the treatment of acute coronary syndrome, pain treatment, and for certain high-risk pregnancy conditions.

For individuals with chronic back pain, NSAID allergy is a risk factor for increased receipt of opioid prescriptions and development of opioid use disorder.

Management

For non-aspirin exacerbated respiratory disease (AERD) NSAID hypersensitivity, a two-step outpatient NSAID oral challenge has been shown to be a safe and effective approach.

  • NSAID reaction within the past 5 years

  • Prior immediate reaction within 3 hours of NSAID ingestion

  • History of reaction to multiple NSAIDs

  • Presence of co-morbid chronic spontaneous urticaria

Oral Challenge

Table 8.3: Proposed two-step protocol for outpatient NSAID oral challenge in patients without AERD. Adapted from Li et al. (2022)
NSAID

Step 1 Dose

(60 minute observation)

Step 2 Dose

(120 minute observation)
Aspirin 40.5 mg 325 mg
Ibuprofen 50 mg 500 mg
Naproxen 60 mg 600 mg

Because of the potential future need for higher dose of aspirin for management of acute coronary syndrome, the second dose for aspirin oral challenge is 325 mg instead of 81 mg.

Of the 262 NSAID challenges performed, over 85% had negative challenges. In addition, 76% of patients included in the study reported a history of urticaria, angioedema, or both (Li et al. 2022). For patients experiencing a positive challenge, 45% had their reaction within 3 hours of NSAID ingestion

Radiocontrast

Background

Modern radiocontrasts are non-ionic, iodinated and either iso-osmolal or low-osmolality. Older radiocontrasts were high-osmolality–which are no longer used intravenously.

The radiocontrast molecular structure is responsible for hypersensitivity reactions–not iodine or seafood allergy. Shellfish allergy is secondary to tropomyosin not iodine.

Infusion Reactions

These are also referred to as “toxic” or “chemotoxic” reactions. Characteristic symptoms include transient warmth/flushing, nausea/vomiting, chest pain, metallic taste, hypertension, and/or vasogal signs.

Immediate Hypersensitivity Reactions

The most common immediate hypersensitivity reaction to radiocontrast is mild urticaria and pruritus, occuring in ~0.9% - 3.1% of patients receiving radiocontrast. Anaphylaxis occurs in 0.02% - 0.04% of patients. Of immediate hypersensitivity reactions, 70% occur within 5 minutes of radiocontrast injection and 96% of severe reactions occur within 20 minutes.

Delayed Hypersensitivity Reactions

The most common delayed hypersensitivity reaction to radiocontrast is a maculopapular exanthem–occurring in 1 to 3% of patients.

Skin Testing

Skin prick testing to the culprit and other radiocontrasts followed by intradermal testing–if skin prick testing is negative–can be useful for identifying an alternative radiocontrast agent. A skin test negative radiocontrast alternative has a 95% NPV.

Intravenous Challenge

Intravenous challenge can be performed to radiocontrast with various protocols–such as 1 mL, 5 mL, 15, mL, and 50 mL (cumulative 71 mL) at 60 minute intervals.

Management

The culprit radiocontrast should be avoided, and an alternative radiocontrast should be used, guided by negative skin testing if available. Other measures to decrease risk of recurrent radiocontrast reaction include: lowering the radiocontrast dose, decreasing the injection speed, and pre-treatment with non-sedating, second generation antihistamines and/or corticosteroids.

Topicals

Antibiotics

The most common topical antibiotics which cause ACD are those found in triple antibiotic ointment—neomycin, polymyxin B, and bacitracin (Choi et al. 2021).

Important

Of patients with neomycin ACD, 50% will cross-react with other aminoglycosides such as gentamicin.

Anesthetics

The most common topical anesthetics which cause ACD are lidocaine and benzocaine.

Note

While patch testing can confirm ACD due to a local anesthetic, not all patients will necessarily develop an allergic reaction to the same anesthetic if used intradermally or subcutaneous—which is often done for dental and dermatologic procedures.

Corticosteroids

Most patients with ACD secondary to corticosteroids have a history of atopy. Because corticosteroids are often not considered initially as a possible cause of ACD, there might be increased use and worsening of a patient’s dermatitis.

ACD due to corticosteroids may produce an “edge effect” or “doughnut-type” reaction–due to the anti-inflammatory effect of the higher concentration of the corticosteroid in the central area compared to the periphery.

Important

If a patient has ACD due to a topical corticosteroid, you should consider propylene glycol as a potential cause—an excipient found in various topical corticosteroids and one of the top 4 causes of ACD due to drugs.

Propylene Glycol

Propylene glycol—an excipient—may be utilized in topical drugs as a softening agent, solvent, moisturizer, or preservative.

Of patients with propylene glycol ACD, 80% have a history of atopic dermatitis.

Important

Propylene glycol is present in various topical emolients, corticosteroids, and calcineurin inhibitors (Tran and Reeder 2020).

Table 8.4: Select topical drugs for treatment of atopic dermatitis by propylene glcyol content.
Topical Propylene glycol-containing Propylene glycol-free
Emolients
Corticosteroids
  • Mometasone furoate ointment 0.1%

  • Triamcinolone acetonide ointment 0.1%

  • Hydrocortisone ointment 2.5%
Calcineurin inhibitors
  • Pimecrolimus cream 1%
  • Tacrolimus ointment 0.03% and 0.1%

Eye Drops

The eyelids are more susceptible to ACD compared to other facial areas—owing to their thin skin 0.55 mm compared to 2 mm, respectively (Amin and Belsito 2006). Therefore, the eyelids may be the only affected area by a drug that comes in contact with the face.

Note

ACD due to eye drops is primarily caused by anti-microbial preservatives rather than the primary drug. Benzylalkonium chloride is the most commonly implicated preservative in patients with history of eye drop reactions (Dear, Palmer, and Nixon 2021).

Table 8.5: Select commercially-available eye drops for common treatment categories by benzylalkonium chloride content
Category Benzyalkonium chloride-containing Benyzlalkonium chloride-free
Antibiotic

  • Ciprofloxacin (Ciloxan)

  • Gatifloxacin (Zymar)

  • Neomycin/Polymyxin B sulfates/Dexamethasone (Maxitrol)

  • Ofloxacin (Ocuflox)

  • Polymyxin B sulfate/Trimethoprim (Polytrim)

  • Tobramycin (Tobrex)

  • Moxifloxacin (Vigamox)

  • Erythromycin ointment (Ilotycin)
Corticosteroid

  • Dexamethasone (Maxidex)

  • Prednisolone acetate

  • Prednisolone sodium phosphate
  • Loteprednol 0.5% ointment
NSAID

  • Keterolac 0.4% (Acular LS)

  • Ketorolac 0.5% (Acular)
  • Keterolac 0.45% (Lotemax)
Gluacoma

  • Brinzolamide (Azopt)

  • Timolol (Timoptic)

  • Tafluprost (Zioptan)

  • Latanoprost (Iyuzeh)

  • Timolol (Timoptic in Ocudose)

  • Dorzolamide/Timolol (Cosopt PF)

References:

https://eyewiki.org/Preservatives_in_Topical_Ophthalmic_Medications#Benzalkonium_chloride_(BAK)

Vaccines

Background

It is estimated that any adverse effect from vaccines occurs in 11.4 per 100,000 administrations.

The most common vaccine adverse reactions are fever and local injection site reactions–which are not hypersensitivity reactions and are not contraindications to future vaccination.

The reported incidence of anaphylaxis is 1.3 case per million doses.

No, egg allergy is not a contraindication to receiving the influenza vaccine.

The amount of egg protein (ovalbumin) is not sufficient (< 1 µg) to provoke a reaction even in the recipients with most severe egg allergy.

Skin Testing

Management

Reaction Type Perform Skin Testing? Vaccine Administration by Skin Testing Result (if applicable)
Delayed reaction (e.g. late-onset urticaria, local arm swelling) No Subsequent dose in usual manner
Immediate reaction without IgE-mediated reaction features (e.g. tingling, flushing, palpitation, sensation of throat closure) No Subsequent dose in usual manner but observe for 30 minutes
Immediate reaction with IgE-mediated reaction features (e.g. urticaria, angioedema, wheezing) Yes

Negative: Usual manner 30 min obs

Positive: Split dose
Anaphylaxis Yes

Negative: Split dose

Positive: Graded dose
Protocol for vaccine split dose administration
Step Volume (mL) of full-dose full-strength for 0.5 mL vaccine dose Dilution Percent of full-dose full-strength for 0.5 mL vaccine dose Observation
1 0.05 Full-strength 10% 30 minutes
2 0.45 Full-strength 90% 30 minutes
Protocol for vaccine graded dose administration
Step Volume (mL) Dilution Percent of full-dose full-strength Observation
1 0.05 1:10 N/A 15 minutes
2 0.05 Full-strength 10% 15 minutes
3 0.1 Full-strength 20% 15 minutes
4 0.15 Full-strength 30% 15 minutes
5 0.2 Full-strength 40% 15 minutes