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s physicians we frequently make quick diagnoses leading to reflex treatments that might not be the most appropriate. Urinary tract infections (UTIs) are common, and, in simple uncomplicated cases, such rapid decisions are often uneventful. In a complicated case, such as the following, however, serious conse- quences could have resulted.Case description
An internist was investigating and treating the recent onset of hypertension in a 33-year-old woman with a history of myasthenia gravis.
Medical history revealed she had a recur- rent thymoma treated with surgical resection, radiotherapy, and chemotherapy. Symptom review was negative except for occasional headaches during menstruation. She was tak- ing hydrochlorothiazide, nadolol, and amlo- dipine for hypertension and cyclosporine and prednisone for myasthenia gravis.
During one of her clinic visits, she com- plained of suprapubic discomfort and urgency, which led to a request for a urinalysis and a urine culture; a copy of results were sent to her family doctor. The urine showed the fol- lowing: 3+ hemoglobin (normal: negative), 6-10/high-power field red blood cells (normal:
0-5/high-power field); urine culture showed mixed organisms (> 100 million colony-forming units/mL). After reviewing the results, her family doctor called her and prescribed a course of norfloxacin (Noroxin), 400 mg twice daily for 7 days.
The patient filled the prescription but did not take it, as she was concerned it might interfere with her other medications. She called the internist to inquire, and the internist advised her not to take norfloxacin, based on the fact that results of her urine tests were not definitive for a UTI and that there was poten- tial for a serious adverse interaction between norfloxacin and cyclosporine. Further ques- tioning by the internist revealed that she was menstruating when her urine was collected.
Results of a repeat urinalysis when she was not menstruating were normal.
Discussion
The patient presented with symptoms sug- gesting a UTI (suprapubic pain and urgency), but the results of urinalysis and urine culture did not confirm an infection. The absence of pyuria argues against a diagnosis of UTI. The positive hemoglobin (3+) and red blood cells in the urine (6-10/high-power field) were likely due to menstrual flow. The urine culture showing mixed organisms (>100 000 colony- forming units/mL) suggested contamination of the urine during collection, not an infection.
The key learning point in this case is the pos- sibility of doing serious harm with no chance of benefit. We performed a literature search in the following databases: MEDLINE (1966 to pres- ent), EMBASE (1988 to present) and Current Contents (1966 to present) using the key words norfloxacin, cyclosporine, drug interaction, and myasthenia gravis. This search revealed that norfloxacin does not increase cyclosporine lev- els in all patients,1 but it can increase them by as much as 2.5 times.2-4 In addition, norfloxacin alone can exacerbate myasthenia gravis symp- toms: double vision, weakness, dysphagia, and shortness of breath developed within hours after receiving the first dose and again 6 months later with rechallenge.5,6
Norfloxacin was both prescribed and dis- pensed in this case despite two warnings in the norfloxacin product monograph published in the Compendium of Pharmaceuticals and This article has been peer reviewed.
Cet article a fait l’objet d’une évaluation externe.
Can Fam Physician 2003;49:176-177.
Case Report: Prescribing caution
When a simple disease isn’t so simple
Cremona Ticea, MD James M. Wright, MD, PHD, FRCPC
Dr Ticea is a family practice resident at the University of Calgary in Alberta. Dr Wright is an Internist/Clinical Pharmacologist and Professor in the Departments of Pharmacology and Therapeutics and of Medicine at the University of British Columbia in Vancouver.
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Specialties.7 Under Precautions it read “Quinolones, including norfloxacin, may exacerbate the signs of myasthenia gravis and lead to life threatening weakness of the respiratory muscles.” Under Drug Interactions it read “Elevated serum levels of cyclo- sporine have been reported with concomitant use with norfl oxacin. Therefore, cyclosporine serum lev- els should be monitored and appropriate cyclosporine dosage adjustments made when these drugs are used concomitantly.”
We wondered why the norfl oxacin was dispensed, given that British Columbia has a sophisticated computer program called PharmaNet, which tracks all drugs dispensed in the province and provides a drug-interaction program to detect potential adverse drug interactions in patients. To test the program we represcribed norfl oxacin to the same patient while she continued to receive cyclosporine. To ensure that the norfloxacin was not dispensed, one of us (C.T.) accompanied the patient to the pharmacy. The PharmaNet drug-interaction program did not raise any warning of the potential adverse interaction between norfl oxacin and cyclosporine in this patient.
In our opinion, this represents a deficiency in the PharmaNet program; however, we are not aware of the prevalence of such defi ciencies. The ePocrates Palm Pilot program also did not list this interaction;
however, in the section on contraindications and cau- tions, it mentions, “caution if myasthenia gravis.”
Conclusion
Physicians should remember the following points when they encounter even “routine” illnesses.
• Sometimes apparently simple conditions, such as UTIs, are not so simple. When laboratory results are not defi nitive, reevaluate patients.
• Exercise caution when a patient has a rare comor- bid condition (myasthenia gravis).
• Beware of drug interactions when patients are taking potentially toxic drugs (cyclosporine).
Computer drug-interaction programs are fallible.
In this case the Compendium of Pharmaceuticals and Specialties provided the necessary information, though it was not easy to locate.
Competing interests None declared
Correspondence to: Dr James M. Wright, Department of Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC V6T 1Z3; e-mail [email protected]
References
1. Jadoul M, Pirson Y, van Ypersele de Strihou C. Norfl oxacin and cyclosporine—a safe combination. Transplantation 1989;47(4):747-8.
2. Thomson DJ, Menkis AH, McKenzie FN. Norfl oxacin-cyclosporine interaction.
Transplantation 1988;46(2):312-3.
3. Adam D, Von Rosenstiel N. Adverse reactions to quinolones, potential toxicities, drug interactions and metabolic effects. Infect Dis Clin Pract 1994;3(Suppl 3):
S177-S81.
4. Radandt JM, Marchbanks CR, Dudley MN. Interactions of fl uoroquinolones with other drugs: mechanisms, variability, clinical signifi cance, and management. Clin Infect Dis 1992;14(1):272-84.
5. Rauser EH, Ariano RE, Anderson BA. Exacerbation of myasthenia gravis by nor- fl oxacin. Ann Pharmacother 1990;24(2):207-8.
6. Adams SL, Mathews J, Grammer LC. Drugs that may exacerbate myasthenia gra- vis. Ann Emerg Med 1984;13(7):532-8.
7. Canadian Pharmacists Association. Compendium of pharmaceuticals and specialties.
36th ed. Ottawa, Ont: Canadian Pharmacists Association; 2001. p. 1051-3.
Editor’s key points
• A patient was inadvertently prescribed a qui- nolone antibiotic for an alleged urinary tract infection while she was taking cyclosporine for myasthenia gravis, despite warnings in the Compendium of Pharmaceuticals and Specialties against this combination.
• A computer drug-interaction monitoring program, PharmaNet, in British Columbia did not fl ag this interaction, nor was it listed on ePocrates except as a caution. Drug databases cannot list all interac- tions and should not be considered infallible.
• Bottom line: exercise caution in prescribing when a patient has a rare condition and is on unusual medications.
Points de repère du rédacteur
• On a prescrit par inadvertance un antibiotique de la famille des quinolones à une patiente soupçonnée d’infection urinaire, alors qu’elle recevait déjà de la cyclosporine pour une myas- thénie grave, et ce même si le risque d’une telle combinaison est signalé dans le Compendium des produits et spécialités pharmaceutiques.
• Cette interaction n’a pas été signalée par un programme informatique de surveillance des interactions médicamenteuses de la Colombie- Britannique appelé Pharmanet, et elle n’était pas non plus mentionnée dans le programme de l’ordinateur de poche ePocrates, sauf comme avertissement. Les bases de données concernant les médicaments ne peuvent pas énumérer toutes les interactions et elles ne doivent pas être consi- dérées comme infaillibles.
• En résumé, il y a lieu d’être particulièrement circonspect quand on fait une prescription à un patient qui souffre d’une maladie rare et qui reçoit une médication inhabituelle.
