LETTERS
ly and cefotaxime administered intravenously for patients withskin and soft-tissue infections. RevInfect Dis 1988;1O(suppll):SI29-31. 3. Peters B, Pinching AJ. Fatalanaphylaxis associated withciprotloxacin in a patientwithAIDS relatedcomplex(letter). Br MedJ 1989;298:605. 4. Wurtz RM, Abrams 0, Becker S, Jacobson MA, Mass MM, Marks SH. Anaphylactoiddrug reactions to ciprofloxacin and rifampicin in HIV-infected patients (letter). Lancet 1989; I:955-6. 5. Kennedy CA, Goetz MB, Mathisen GE. Ciprofloxacin-induced anaphylactoidreactions in patientsinfected withthe humanimmunodeficiency virus(letter). West J Med 1990;153:563-4.
Laryngeal edema related to ciprotloxacin therapy
Fluconazole-nortriptyline drug interaction
TOTHEEDITOR: We describe a rare occurrence of delayed hypersensitivity reaction to ciprofloxacin that resulted in neck swelling, difficulty swallowing, and laryngeal edema. A 95-year-old woman presented to the hospital complaining of neckswelling anddifficulty swallowing bothliquids andsolids. Eighteen hours priorto admission, she hadbeenstarted onciprotloxacin 250mg po bidfor treatment of a pseudomonal urinary tract infection. The patienthad a history of diabetesmellitus, temporal arteritis, epilepsy, coronary artery disease, and peripheral vascular disease.Maintenance medications included prednisone 10mg/dpo, human insulin 70/30 22 units sc qam,phenobarbital 60 mgpo hs,furosemide 20 mgpoqam,and pentoxifylline 400 mg po tid. The patienthad known allergies to sulfa drugs, phenytoin, contrast dye,andbeefinsulin. Physical examination revealed fullness of thetongue andof the submandibular triangle bilaterally. The neckwas mildly tenderto palpation. Edemaof the arytenoid cartilages anddifficulty in swallowing salivawerealsonoted. No stridor, wheezing, drooling, or hives were observed. Neck X-ray showed posterior soft-tissueswelling. Immediate treatment consisted of methylprednisolone 125 mg iv and diphenhydramine hydrochloride 25 mg iv. During hospitalization, the patient received prednisone 20 mg/d po (also for her temporal arteritis) and diphenhydramine hydrochloride 50 mg po q6h.She alsoreceived dextrose 50% 25 mL iv on account of a blood glucose reading of 2.7 mmol/L (normal 4.4-6.7).The patient'slowblood glucose concentration wasattributed to hernoteating themorningof admission, butstilltaking her insulin. Vital signs andotherlaboratory valueswere normal. Three dayspostadmission, the patient continued to complain of difficulty swallowing solids and a barium swallow revealed a hiatal herniawith esophageal retlux. Fourdayspostadmission, she wasdischarged on her maintenance medications as well as ranitidine 150mgpo bidforretlux. Davis et aI. reported on IS patients who developed anaphylactoid reactions of the circulatory, respiratory, or cutaneous systems with ciprofloxacin. One patient experienced laryngeal edema and urticaria. Thirteen patients experienced symptoms within 5--60 minutes of their first 200- to 750-mg dose of ciprofloxacin. When the reactions occurred, 73 percent of the patients were not taking any other drugs concomitantly.' Leal Del Rosal et aI. reported on a patient who developed a severe rash and laryngeal edema following ciprofloxacin therapy; both reactions subsequently resolved.' Three other groups of investigators described 6 patients with AIDS or AIDS-related complex who developed anaphylactoid reactions after receiving ciprofloxacin for a second time after 10-14 days without treatment with the drug.r" At least 3 patients had stopped taking the drug during the first course of therapy because of a possible adverse reaction," Physicians should be aware of the possibility of a delayed hypersensitivity reaction associated with ciprofloxacin.
TOTHEEDITOR: Nortriptyline is a tricyclic antidepressant with an established therapeutic serum concentration of 50-ISO ng/mL. Failure of patients to respond to the drug generally is seen at concentrations below 50 ng/mL; concentrations above 150 ng/mL usually are associated with increased toxicity rather than increased benefit. The metabolism of nortriptyline can be influenced by hepatic enzyme inducers such as the barbiturates, which have been reported to decrease serum nortriptyline concentrations" Hepatic enzyme inhibitors such as cimetidine (an imidazole compound) have been reported to increase steady-state nortriptyline concentrations.' Fluconazole is an imidazole antifungal agent approved for the treatment of oropharyngeal and esophageal candidiasis, as well as cryptococcal meningitis. Imidazole compounds are known to inhibit hepatic drug metabolism.' Fluconazole has been reported to cause increased serum concentrations of phenytoin, cyclosporine, tolbutamide, and warfarin." We describe a suspected new drug interaction between fluconazole and nortriptyline; this patient's steady-state serum nortriptyline concentration was significantly increased by concomitant fluconazole therapy. A 65-year-old woman (52 kg) who underwent a cardiac transplant one year previously wasadmitted on October 15for pneumonia and a rejection episode. The patient's past medical history was significant for osteoporosis, collapsed spinal vertebrae resulting in chronic pain,pneumonia, pancreatitis, andconstipation.She hada questionable allergy to sulfonamides. Medications on admission included cyclospotine, sustained-released morphine, metoclopramide, andbumetanide. Shealsohadbeentaking nortriptyline 75 mg/d fordepression andas an adjunct to paincontrol for one month priorto admission withgoodcompliance. A trough serum nortriptyline concentration was 149ng/mL on October 25.The patient's pneumonia did not improve on antibiotic therapy andantifungal therapy wasinitiated onOctober 26.Shewasgiven tluconazole 200mgpoonce, followed bydaily administration of a IOD-mg dose thereafter. Sheappeared slightly sedated on October 29, and the morphine dosage wassubsequently decreased. Hernortriptyline dosage alsowasdecreased thatday to 50 mg/dfor fourdays.The 75mg/ddosage was resumed on November 2, as the patient wasmoreawake and alert. A trough serum nortriptyline concentration wasdrawn on November 7 andit wasreported to be252ng/mL. Nortriptyline wasdiscontinued at thattime. A pharmacokinetic interaction between fluconazole and nortriptyline is suggested by the fact that this patient's trough steady-state serum concentration of nortriptyline increased from 149 to 252 ng/mL when fluconazole was initiated and the dosage of nortriptyline remained at 75 mg/d. We are not aware of any reports of drug interactions between fluconazole and other tricyclic antidepressants. Fluconazole has a unique structure that includes an imidazole ring. Many other pharmaceutical agents that contain this ring (e.g., cirnetidine, ketoconazole, omeprazole) have been shown to inhibit the cytochrome P-450-dependent enzyme system.' Toxic serum concentrations of drugs metabolized via this system have been clinically observed and experimentally proven upon their concomitant administration with imidazole-containing drugs.' Because nortriptyline is metabolized by the cytochrome P-450 enzyme system," we can hypothesize that fluconazole increased the steady-state serum concentrations of nortriptyline in this patient by inhibiting hepatic metabolism of the drug.
ANNE M. BACIEWICZ, Pharm.D.
ClinicalPharmacist in Medicine Departmentof PharmacyServices University Hospitals of Cleveland Cleveland, Ohio44106 GEORGE GEORGES, M.D.
Residentin Medicine MAIER BECKER, M.D.
Residentin Medicine ADRIAN M. SCHNALL, M.D.
AssistantClinicalProfessor Department of Medicine REFERENCES I. Davis H, McGoodwin E, Reed TG. Anaphylactoid reactions reported after treatmentwith ciprotloxacin. AnnIntern Med 1989; 111:1041-3. 2. Leal Del Rosal P, Leal Del Rosal L, Magana Garcia JL, Riosvelasco A. Comparative, double-blind studyof ciprofloxacin administered oral-
1456 •
The Annals ofPharmacotherapy
•
RICHARD H. GANNON, Pharm.D.
AssistantDirector, ClinicalPharmacyServices Director, Pain ControlService Department of Pharmacy HartfordHospital 80 SeymourStreet Hartford. Connecticut 06115 AssistantClinicalProfessor Schoolof Pharmacy University of Connecticut
1992 November, Volume 26
Downloaded from aop.sagepub.com at UNIV CALIFORNIA SAN DIEGO on December 21, 2015
ly and cefotaxime administered intravenously for patients withskin and soft-tissue infections. RevInfect Dis 1988;1O(suppll):SI29-31. 3. Peters B, Pinching AJ. Fatalanaphylaxis associated withciprotloxacin in a patientwithAIDS relatedcomplex(letter). Br MedJ 1989;298:605. 4. Wurtz RM, Abrams 0, Becker S, Jacobson MA, Mass MM, Marks SH. Anaphylactoiddrug reactions to ciprofloxacin and rifampicin in HIV-infected patients (letter). Lancet 1989; I:955-6. 5. Kennedy CA, Goetz MB, Mathisen GE. Ciprofloxacin-induced anaphylactoidreactions in patientsinfected withthe humanimmunodeficiency virus(letter). West J Med 1990;153:563-4.
Laryngeal edema related to ciprotloxacin therapy
Fluconazole-nortriptyline drug interaction
TOTHEEDITOR: We describe a rare occurrence of delayed hypersensitivity reaction to ciprofloxacin that resulted in neck swelling, difficulty swallowing, and laryngeal edema. A 95-year-old woman presented to the hospital complaining of neckswelling anddifficulty swallowing bothliquids andsolids. Eighteen hours priorto admission, she hadbeenstarted onciprotloxacin 250mg po bidfor treatment of a pseudomonal urinary tract infection. The patienthad a history of diabetesmellitus, temporal arteritis, epilepsy, coronary artery disease, and peripheral vascular disease.Maintenance medications included prednisone 10mg/dpo, human insulin 70/30 22 units sc qam,phenobarbital 60 mgpo hs,furosemide 20 mgpoqam,and pentoxifylline 400 mg po tid. The patienthad known allergies to sulfa drugs, phenytoin, contrast dye,andbeefinsulin. Physical examination revealed fullness of thetongue andof the submandibular triangle bilaterally. The neckwas mildly tenderto palpation. Edemaof the arytenoid cartilages anddifficulty in swallowing salivawerealsonoted. No stridor, wheezing, drooling, or hives were observed. Neck X-ray showed posterior soft-tissueswelling. Immediate treatment consisted of methylprednisolone 125 mg iv and diphenhydramine hydrochloride 25 mg iv. During hospitalization, the patient received prednisone 20 mg/d po (also for her temporal arteritis) and diphenhydramine hydrochloride 50 mg po q6h.She alsoreceived dextrose 50% 25 mL iv on account of a blood glucose reading of 2.7 mmol/L (normal 4.4-6.7).The patient'slowblood glucose concentration wasattributed to hernoteating themorningof admission, butstilltaking her insulin. Vital signs andotherlaboratory valueswere normal. Three dayspostadmission, the patient continued to complain of difficulty swallowing solids and a barium swallow revealed a hiatal herniawith esophageal retlux. Fourdayspostadmission, she wasdischarged on her maintenance medications as well as ranitidine 150mgpo bidforretlux. Davis et aI. reported on IS patients who developed anaphylactoid reactions of the circulatory, respiratory, or cutaneous systems with ciprofloxacin. One patient experienced laryngeal edema and urticaria. Thirteen patients experienced symptoms within 5--60 minutes of their first 200- to 750-mg dose of ciprofloxacin. When the reactions occurred, 73 percent of the patients were not taking any other drugs concomitantly.' Leal Del Rosal et aI. reported on a patient who developed a severe rash and laryngeal edema following ciprofloxacin therapy; both reactions subsequently resolved.' Three other groups of investigators described 6 patients with AIDS or AIDS-related complex who developed anaphylactoid reactions after receiving ciprofloxacin for a second time after 10-14 days without treatment with the drug.r" At least 3 patients had stopped taking the drug during the first course of therapy because of a possible adverse reaction," Physicians should be aware of the possibility of a delayed hypersensitivity reaction associated with ciprofloxacin.
TOTHEEDITOR: Nortriptyline is a tricyclic antidepressant with an established therapeutic serum concentration of 50-ISO ng/mL. Failure of patients to respond to the drug generally is seen at concentrations below 50 ng/mL; concentrations above 150 ng/mL usually are associated with increased toxicity rather than increased benefit. The metabolism of nortriptyline can be influenced by hepatic enzyme inducers such as the barbiturates, which have been reported to decrease serum nortriptyline concentrations" Hepatic enzyme inhibitors such as cimetidine (an imidazole compound) have been reported to increase steady-state nortriptyline concentrations.' Fluconazole is an imidazole antifungal agent approved for the treatment of oropharyngeal and esophageal candidiasis, as well as cryptococcal meningitis. Imidazole compounds are known to inhibit hepatic drug metabolism.' Fluconazole has been reported to cause increased serum concentrations of phenytoin, cyclosporine, tolbutamide, and warfarin." We describe a suspected new drug interaction between fluconazole and nortriptyline; this patient's steady-state serum nortriptyline concentration was significantly increased by concomitant fluconazole therapy. A 65-year-old woman (52 kg) who underwent a cardiac transplant one year previously wasadmitted on October 15for pneumonia and a rejection episode. The patient's past medical history was significant for osteoporosis, collapsed spinal vertebrae resulting in chronic pain,pneumonia, pancreatitis, andconstipation.She hada questionable allergy to sulfonamides. Medications on admission included cyclospotine, sustained-released morphine, metoclopramide, andbumetanide. Shealsohadbeentaking nortriptyline 75 mg/d fordepression andas an adjunct to paincontrol for one month priorto admission withgoodcompliance. A trough serum nortriptyline concentration was 149ng/mL on October 25.The patient's pneumonia did not improve on antibiotic therapy andantifungal therapy wasinitiated onOctober 26.Shewasgiven tluconazole 200mgpoonce, followed bydaily administration of a IOD-mg dose thereafter. Sheappeared slightly sedated on October 29, and the morphine dosage wassubsequently decreased. Hernortriptyline dosage alsowasdecreased thatday to 50 mg/dfor fourdays.The 75mg/ddosage was resumed on November 2, as the patient wasmoreawake and alert. A trough serum nortriptyline concentration wasdrawn on November 7 andit wasreported to be252ng/mL. Nortriptyline wasdiscontinued at thattime. A pharmacokinetic interaction between fluconazole and nortriptyline is suggested by the fact that this patient's trough steady-state serum concentration of nortriptyline increased from 149 to 252 ng/mL when fluconazole was initiated and the dosage of nortriptyline remained at 75 mg/d. We are not aware of any reports of drug interactions between fluconazole and other tricyclic antidepressants. Fluconazole has a unique structure that includes an imidazole ring. Many other pharmaceutical agents that contain this ring (e.g., cirnetidine, ketoconazole, omeprazole) have been shown to inhibit the cytochrome P-450-dependent enzyme system.' Toxic serum concentrations of drugs metabolized via this system have been clinically observed and experimentally proven upon their concomitant administration with imidazole-containing drugs.' Because nortriptyline is metabolized by the cytochrome P-450 enzyme system," we can hypothesize that fluconazole increased the steady-state serum concentrations of nortriptyline in this patient by inhibiting hepatic metabolism of the drug.
ANNE M. BACIEWICZ, Pharm.D.
ClinicalPharmacist in Medicine Departmentof PharmacyServices University Hospitals of Cleveland Cleveland, Ohio44106 GEORGE GEORGES, M.D.
Residentin Medicine MAIER BECKER, M.D.
Residentin Medicine ADRIAN M. SCHNALL, M.D.
AssistantClinicalProfessor Department of Medicine REFERENCES I. Davis H, McGoodwin E, Reed TG. Anaphylactoid reactions reported after treatmentwith ciprotloxacin. AnnIntern Med 1989; 111:1041-3. 2. Leal Del Rosal P, Leal Del Rosal L, Magana Garcia JL, Riosvelasco A. Comparative, double-blind studyof ciprofloxacin administered oral-
1456 •
The Annals ofPharmacotherapy
•
RICHARD H. GANNON, Pharm.D.
AssistantDirector, ClinicalPharmacyServices Director, Pain ControlService Department of Pharmacy HartfordHospital 80 SeymourStreet Hartford. Connecticut 06115 AssistantClinicalProfessor Schoolof Pharmacy University of Connecticut
1992 November, Volume 26
Downloaded from aop.sagepub.com at UNIV CALIFORNIA SAN DIEGO on December 21, 2015
