The Family Practice Newsletter
The Ohio University College of Osteopathic Medicine
The Ohio Northern University Raabe College of Pharmacy
Doctors Hospital Family Practice
Volume 5, Issue 7
March, 2006
What does “Allergic to Sulfa” really mean?
Stephanie Gibson, Pharm.D., R.Ph.
Many patients report having an allergic reaction to medications that contain “sulfa”. This is usually based on the
fact that they had a reaction to a sulfa containing medication in the past. Once experiencing this reaction, patients become
very hesitant to take “sulfa” medications and physicians become very hesitant to prescribe medications whose chemical
structure contains the sulfur ion. Many medications exist which contain a sulfur ion such as diuretics, sulfonylureas, and 5HT3 receptor antagonists. The question begs how can you determine if and what medications are safe to use in this group of
patients?
Two types of allergic reactions to sulfonamide chemicals are described by Johnson and colleagues and are thought
to occur as a result of the medication’s chemical structure. The sulfa containing medications which most commonly cause a
reaction contain a particular structure, a sulfonylarylamine. This component is responsible for severe allergic reactions,
thought to be mediated by IgE. Characteristics of this type of reaction include: onset within 1-3 days of exposure, a
maculopapular eruption or urticarial rash, and resolution upon discontinuation of the agent. It is important to remember that
anaphylaxis may occur upon second exposure. The second type of reaction typically develops within 7-14 days after
exposure and presents as fever with a non-urticarial rash. When compared to the structure of the sulfonylarylamines, the
second types of reactions are typically seen with medications having an extra amine group on the aromatic ring. Since not
all medications which contain a sulfur atom contain one of the structures mentioned above, it is most likely that patients will
not react to those medications. The following charts summarize FDA recommendations for use of sulfa containing
medications in patients with a history of sulfa allergy.
Contraindicated for use in patients with sulfa allergy
Medication class
Medication name
comments
Antibiotics
Sulfadiazine, sulfamethoxazole,
Oral, topical, ophthalmic, and vaginal products
sulfisaxazole, sulfapyridine
Carbonic anhydrase
Acetazolamide (Diamox)
inhibitors
COX-2 Inhibitors
Celecoxib (Celebrex)
Loop diuretics
Torsemide (Demadex)
Contraindicated in patients allergic to
sulfonylureas
Thiazide and thiazide-like Chlorothiazide (Diuril)
diuretics
Hydrochlorothiazide
Chlorthalidone (Hygroton)
Indapamide (Lozol)
Other
Sulfasalazine(Azulfidine)
Zonisamide (Zonegran)
Exercise caution when prescribing the following medications to patients with a sulfa allergy
Medication class
Medication name
comments
Carbonic anhydrase inhibitors
Brinzolamide (Azopt)
Ophthalmic preps are systemically
Dorzolamide (Trusopt)
absorbed, severe reactions can recur
Protease Inhibitors
Amprenavir (Agenerase)
Fosamprenavir (Lexiva)
Loop Diuretics
Bumetanide (Bumex)
Severe reactions have occurred.
Ethacrynic acid is the only loop
diuretic that does not contain a sulfa
group.
Thiazide-like diuretics
Metolazone (Zaroxolyn, Mykrox)
Other
Tamsulosin (Flomax)
Tipranavir (Aptivus)
Many factors play a role when making the decision to use one of the above mentioned medications in a patient with a sulfa
allergy: the severity of the reaction and the medication that the patient was using when the reaction occurred. If a patient had
a previous life-threatening reaction, than it is recommended to not re-challenge with any of the medications listed as
“precaution”, as they are more likely to react to other sulfa containing medications. If the reaction was not severe and the
likelihood of a reaction is low based upon the FDA recommendations, then it may be safe to rechallenge the patient. If so,
the patient must be monitored closely when administering the first dose of the medication.
1. Johnson KK, Green DL, Rife JP, Limon L. Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother. 2005;29:290-301.
2. Robinson JL, Hameed T, Carr S. Practical Aspects of Choosing an Antibiotic for patients with a Reported Allergy to an Antibiotic. Clin Inf Dis.
2002;35:26-31.
3. Cross-Reactivity of Sulfonamide Drugs. Pharmacist’s Letter/ Prescriber’s Letter 2005; 21(1-8): 211113.
The Use of Quinolones in Uncomplicated Urinary Tract Infections
Kelly Stanforth, Pharm.D.
Quinolones are frequently prescribed for treatment of uncomplicated urinary tract infections (UTI). This prescribing
trend is most likely due to the ease of once daily dosing and the perceived increase in adherence to the treatment regimen by
the patient. The excessive use of a broad-spectrum antibiotic for the treatment of an uncomplicated infection is alarming and
may make these agents less effective in treating more serious infections.
In 1999, the Infectious Disease Society of America (IDSA) recommended trimethoprim-sulfamethoxazole (Bactrim®) as
first line treatment for uncomplicated UTIs. A caveat to this recommendation was the fact that increased resistance to this
agent was rising and public health officials recommended the use of narrow-spectrum antibiotics for treatment whenever
possible. The concern over resistance to Bactrim® resulted in the escalating use of quinolones as a first line treatment
strategy.
Using data from the National Ambulatory Medical Care and National Hospital Ambulatory Medical Care Surveys,
Kallan and colleagues reported antibiotic prescribing patterns for uncomplicated UTIs in the United States from 2000 to
2002. Data obtained allowed the researchers to evaluate 2638 females with isolated outpatient UTIs. They found that
quinolones were prescribed in 48 percent of patients, and Bactrim® in 33 percent of patients. Approximately one-third of the
quinolones prescribed were broad spectrum agents such as levofloxacin (Levaquin ®), moxifloxacin (Avelox®), and
gatifloxacin (Tequin®) versus the narrow spectrum agents such as ciprofloxacin (Cipro ®).
Additionally, Kallan and colleagues reported that the prescribing of quinolones was not correlated with areas of high
Bactrim® resistance. Quinolones were prescribed more frequently in the Northeast which coincidentally is the area of the
nation with the lowest resistance rates to Bactrim®. On the other hand, the lowest rate of quinolone use was in the West,
which is the region with the uppermost resistance to Bactrim®.
Due to kinetic parameters, the efficacy of quinolones in the treatment of UTIs is not generalizable to all members of the
class. Moxifloxacin (Avelox®) does not achieve high concentrations in the urine and should not be used for the treatment of
UTIs. Gatifloxacin (Tequin®) is able to achieve high urine concentrations; however, the medication was recently discontinued
by the manufacturer due to the incidence of hypo and hyperglycemia in diabetics and the elderly. Ciprofloxacin (Cipro ®) and
levofloxacin (Levaquin®) have excellent bioavailability, achieve high urine concentrations, and their ability to penetrate the
renal tissue is excellent.
To limit resistance to quinolones, use should be limited to patients who have severe symptoms and an allergy to
Bactrim® or have received treatment with an alternative antibiotic in the previous three months or live in
communities with increased prevalence of E. coli resistance to Bactrim®.
1.
2.
3.
4.
Treatment of uncomplicated urinary tract infections. Pharmacist’s Letter 2006; 22 (6): 220610.
Miller LG, Tang AW. Treatment of uncomplicated urinary tract infections in an era of increasing antimicrobial resistance. Mayo Clin Proc 2004;
79 (8): 1048-1054.
Gupta K, Hooton TM, Stamm WE. Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract
infections. Ann Intern Med 2001; 135: 41-50.
Hooton TM, Besser R, Foxman B, Fritsche TR, Nicolle LE. Acute uncomplicated cystitis in an era of increasing antibiotic resistance: a proposed
approach to empirical therapy. CID 2004; 39: 75-80.
Edited by Stephanie Gibson, Pharm.D. Comments can be sent to sgibson@ohiohealth.com