Adverse Drug Event
Prolonged Cholestatic Jaundice Associated With Flurbiprofen
Journal of Pharmacy Practice 2014, Vol. 27(4) 396-398 ª The Author(s) 2013 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0897190013515706 jpp.sagepub.com
Serkan Dogan, MD1, Mehmet Celikbilek, MD2, Kutay Demirkan, MD3, Semih Yilmaz, MD4, Kemal Deniz, MD5, Sebnem Gursoy, MD1, and Mehmet Yucesoy, MD1
Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia. Keywords drug information, flurbiprofen, medication safety, liver injury, cholestatic, hepatitis
Introduction
Case Report
Flurbiprofen (Majezik, marketed by Sanovel, Turkey) is a widely prescribed nonsteroidal anti-inflammatory drug (NSAID) in Turkey, mainly used for the treatment of inflammatory disorders and pain relief. Similar to other NSAIDs, the most common adverse effects occur in the gastrointestinal tract (risk of ulceration, bleeding, perforation, etc), with increased risks of cardiovascular and thrombotic events and renal toxicity. However, hepatotoxic side effects remain very unusual.1,2 Borderline elevation of 1 or more liver function tests may occur in up to 15% of the patients taking NSAIDs; rare cases of severe hepatic reactions, including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, some with fatal outcomes, have been reported.3 Flurbiprofen-induced liver cholestasis is extremely rare. We searched the literature in PubMed for a combination of the terms ‘‘cholestasis,’’ ‘‘flurbiprofen,’’ and ‘‘liver injury.’’ Only 3 cases have been described in the current literature.4-6 In one of these cases, hepatotoxicity was reported after long-term use of twice daily doses of 100 mg of flurbiprofen, in which the patient had received flurbiprofen for symptoms of rheumatoid arthritis. Different from our patient, jaundice was reported to have rapidly resolved with conservative treatment over 2 or 3 weeks. The other case was reported in a Spanish patient. The third report was a case–control study. A total of 88 cases and 178 controls were included. A total of 22 cases had been exposed to NSAIDs. Of them, 1 was exposed to flurbiprofen. Liver enzymes had returned to normal values after discontinuation of the drug. To the best of our knowledge, there is no report in the literature related to prolonged icterus associated with flurbiprofen. In our patient, it was shown that the use of flurbiprofen was associated with cholestasis without ductopenia.
A 28-year-old man presented to our hospital with a 1-week history of pruritus and jaundice. He did not have any symptoms such as fever, nausea, emesis, abdominal pain, change in bowel habits, or new rash prior to admission. The patient had a history of right arm weakness and right-sided, belowknee amputation caused by an accident. One month before the admission, the patient was prescribed flurbiprofen (100 mg twice daily) by his general practitioner for the treatment of myalgia and arthralgia. He had not traveled recently to any outside region, took no other medications or herbal supplements, had no known allergies to any medications, had not used intravenous drugs, had never consumed alcohol, and had not ingested wild mushrooms. He had a history of smoking of 10 cigarettes daily. His family history was negative for liver diseases. Moreover, he had no history of industrial exposure to any kind of toxic substances or a history of a recent contact with an ill person.
1 Erciyes University, Medical School, Department of Gastroenterology, Kayseri, Turkey 2 Bozok University, Medical School, Department of Gastroenterology, Yozgat, Turkey 3 Hacettepe University, Medical School, Department of Pharmacology, Ankara, Turkey 4 Erciyes University, Medical School, Department of Internal Medicine, Kayseri, Turkey 5 Erciyes University, Medical School, Department of Pathology, Kayseri, Turkey
Corresponding Author: Serkan Dogan, Erciyes University, Medical School, Department of Gastroenterology, Talas Street, Kayseri 38038, Turkey. Email: [email protected]
Downloaded from jpp.sagepub.com at UCSF LIBRARY & CKM on April 23, 2015
Dogan et al
397
Table 1. Laboratory Data. Variable Tbil, mg/dL Dbil, mg/dL ALP, U/L GGT, IU/L ALT, U/L AST, U/L
Referange race, adults
On admission
7 days
3 months after admission
6 months after admission
0.3-1.2
Prolonged Cholestatic Jaundice Associated With Flurbiprofen
Journal of Pharmacy Practice 2014, Vol. 27(4) 396-398 ª The Author(s) 2013 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0897190013515706 jpp.sagepub.com
Serkan Dogan, MD1, Mehmet Celikbilek, MD2, Kutay Demirkan, MD3, Semih Yilmaz, MD4, Kemal Deniz, MD5, Sebnem Gursoy, MD1, and Mehmet Yucesoy, MD1
Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia. Keywords drug information, flurbiprofen, medication safety, liver injury, cholestatic, hepatitis
Introduction
Case Report
Flurbiprofen (Majezik, marketed by Sanovel, Turkey) is a widely prescribed nonsteroidal anti-inflammatory drug (NSAID) in Turkey, mainly used for the treatment of inflammatory disorders and pain relief. Similar to other NSAIDs, the most common adverse effects occur in the gastrointestinal tract (risk of ulceration, bleeding, perforation, etc), with increased risks of cardiovascular and thrombotic events and renal toxicity. However, hepatotoxic side effects remain very unusual.1,2 Borderline elevation of 1 or more liver function tests may occur in up to 15% of the patients taking NSAIDs; rare cases of severe hepatic reactions, including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, some with fatal outcomes, have been reported.3 Flurbiprofen-induced liver cholestasis is extremely rare. We searched the literature in PubMed for a combination of the terms ‘‘cholestasis,’’ ‘‘flurbiprofen,’’ and ‘‘liver injury.’’ Only 3 cases have been described in the current literature.4-6 In one of these cases, hepatotoxicity was reported after long-term use of twice daily doses of 100 mg of flurbiprofen, in which the patient had received flurbiprofen for symptoms of rheumatoid arthritis. Different from our patient, jaundice was reported to have rapidly resolved with conservative treatment over 2 or 3 weeks. The other case was reported in a Spanish patient. The third report was a case–control study. A total of 88 cases and 178 controls were included. A total of 22 cases had been exposed to NSAIDs. Of them, 1 was exposed to flurbiprofen. Liver enzymes had returned to normal values after discontinuation of the drug. To the best of our knowledge, there is no report in the literature related to prolonged icterus associated with flurbiprofen. In our patient, it was shown that the use of flurbiprofen was associated with cholestasis without ductopenia.
A 28-year-old man presented to our hospital with a 1-week history of pruritus and jaundice. He did not have any symptoms such as fever, nausea, emesis, abdominal pain, change in bowel habits, or new rash prior to admission. The patient had a history of right arm weakness and right-sided, belowknee amputation caused by an accident. One month before the admission, the patient was prescribed flurbiprofen (100 mg twice daily) by his general practitioner for the treatment of myalgia and arthralgia. He had not traveled recently to any outside region, took no other medications or herbal supplements, had no known allergies to any medications, had not used intravenous drugs, had never consumed alcohol, and had not ingested wild mushrooms. He had a history of smoking of 10 cigarettes daily. His family history was negative for liver diseases. Moreover, he had no history of industrial exposure to any kind of toxic substances or a history of a recent contact with an ill person.
1 Erciyes University, Medical School, Department of Gastroenterology, Kayseri, Turkey 2 Bozok University, Medical School, Department of Gastroenterology, Yozgat, Turkey 3 Hacettepe University, Medical School, Department of Pharmacology, Ankara, Turkey 4 Erciyes University, Medical School, Department of Internal Medicine, Kayseri, Turkey 5 Erciyes University, Medical School, Department of Pathology, Kayseri, Turkey
Corresponding Author: Serkan Dogan, Erciyes University, Medical School, Department of Gastroenterology, Talas Street, Kayseri 38038, Turkey. Email: [email protected]
Downloaded from jpp.sagepub.com at UCSF LIBRARY & CKM on April 23, 2015
Dogan et al
397
Table 1. Laboratory Data. Variable Tbil, mg/dL Dbil, mg/dL ALP, U/L GGT, IU/L ALT, U/L AST, U/L
Referange race, adults
On admission
7 days
3 months after admission
6 months after admission
0.3-1.2
