Acute hepatocellular and cholestatic injury in a patient taking celecoxib

Nachimuthu, Senthil; Volfinzon, Leonid; Gopal, Latha Nachimuthu

doi:10.1136/pmj.77.910.548

Cited by 51 publications

(18 citation statements)

References 9 publications

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“…These results are in agreement with Nachimuthu et al (2001) observation of celecoxib in clinical trials [23]. The activities of AST, ALT, and ALP are commonly used as biochemical indicators of liver functions.…”

Section: Discussionsupporting

confidence: 89%

Comparing the Toxic Effects of Nonsteroidal Anti-Inflammatory Drugs (Celecoxib and Ibuprofen) on Heart, Liver, and Kidney in Rats

Aziz

Ouda

Ubaid

2018

Asian J Pharm Clin Res

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Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) do not reverse the disease progression, but they provide relief from pain and inflammation by inhibiting cyclooxygenase (COX) enzymes mediating the inflammatory pathway. Our aim was to make a meaningful comparison of both selective and non-selective COX-2 inhibitor to evaluate their toxic effects by measuring biochemical and histological alterations of heart, liver, and kidney.Methods: This study was conducted on 18 Sprague-Dawley rats of both sexes for 30 days, rats were divided into three groups (control group, ibuprofen group, and celecoxib group) each group included six rats. Results:The results are revealed that serum level of alanine aminotransferase, aspartate aminotransferase, alkaline phosphates, and total serum bilirubin was significantly increased (p<0.05) in ibuprofen and celecoxib group when compared with control, the highest level in celecoxib group, also serum level of urea was significantly elevated (p<0.05) in ibuprofen group when compared with control and celecoxib groups. Histopathological changes in cardiac tissue represented by vascular congestion and pericardial infiltration which are more prominent in celecoxib group, the changes in liver tissue revealed by vascular congestion and mild portal tract inflammation which is chronic in celecoxib group, while histological alterations in kidney tissue represented by severe vascular congestion with tubular necrosis which is more prominent in ibuprofen group. Conclusion:Both ibuprofen and celecoxib group have toxic effects on heart, liver, and kidney represented by the biochemical and histopathological findings.

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Section: Discussionsupporting

confidence: 89%

Comparing the Toxic Effects of Nonsteroidal Anti-Inflammatory Drugs (Celecoxib and Ibuprofen) on Heart, Liver, and Kidney in Rats

Aziz

Ouda

Ubaid

2018

Asian J Pharm Clin Res

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“…Celecoxib-induced nephrotoxicity has been reported in the form of acute interstitial (tubulo)nephritis [3][4][5][6][7][8][9], nephrotic syndrome [3], membranous glomerulopathy [7], papillary necrosis [8] and unbiopsied acute renal failure [1]. Celecoxib-induced hepatotoxicity has been reported as a hepatocellular [2],cholestatic [10][11][12][13],or combined pattern [14].…”

mentioning

confidence: 99%

Late‐onset celecoxib‐induced combined hepato‐nephrotoxicity

Tabibian

Kaufman³

2008

Brit J Clinical Pharma

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Celecoxib is a commonly used selective cyclooxygenase (COX)-2 inhibitor. Sporadic cases of hepatic or renal toxicity have been described with its use. All but three of these cases were reported with short-term use, typically a couple of days or weeks [1][2][3]. We report the first known case of late-onset celecoxib-induced hepato-nephrotoxicity, of which we obtained histological evidence.We present the case of a 56-year-old hypertensive man on ramipril 10 mg day -1 for >3 years who was prescribed celecoxib 200 mg one to two tablets per day for osteoarthritic pain.Baseline laboratory at the time of celecoxib prescription showed blood urea nitrogen (BUN) 16 mg dl(normal 35-110 U l -1 ) and total bilirubin (TBil) 0.5 mg dl -1 (normal 0.3-1.2 mg dl -1 ). He was a nondrinker and nonsmoker with no known risk factors for liver or renal disease.Ten months after prescription of celecoxib, the patient described intermittent right upper quadrant pain, fatigue, and decreased appetite. Over the course of two more months, his symptoms progressed to lethargy and jaundice, requiring hospitalization. He described having had progressively dark urine and pale stools for 2 weeks. His examination showed temperature 36.2°C, blood pressure 140/68 mmHg, pulse 80 per minute and respiration 20 per minute. There was scleral icterus, but no palmar erythema or spider angiomata. The neck was supple without lymphadenopathy.The heart was regular and lungs were clear. The abdomen was benign, without hepatosplenomegaly or ascites. There was no peripheral oedema. Laboratory tests on admission were haemoglobin 12.4 g dl -1 , white blood cells 16 000 ml -1 , platelets 283 000 ml -1 , prothrombin time 12.4 s, BUN 109 mg dl -1 , Cr 5.2 mg dl -1 , ALT 3 U l -1 , AST 17 U l -1 , ALK 77 U l -1 , TBil 32.4 mg dl -1 , direct bilirubin 28.7 mg dl -1 and albumin 4.1 g dl -1 . The antinuclear and hepatitis A IgM antibodies, hepatitis B surface antigen, hepatitis B core IgM antibodies, and hepatitis C antibodies were negative. Abdominal ultrasound and computed tomography were normal.Liver and renal biopsy specimens were obtained within 24 h of admission (Figure 1) and were suggestive of druginduced toxicity. Celecoxib was stopped, with ensuing rapid symptomatic and biochemical improvement. At 7 days, laboratory tests showed BUN 19 mg dl -1 , Cr 1.9 mg dl -1 and TBil 8.7 mg dl -1 , and the patient was discharged. At 6 weeks' follow-up, laboratory tests were BUN 7 mg dl -1 , Cr 1

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“…41 Although clinically relevant hepatoxicity occurs more frequently with NSAIDs than with celecoxib, 42 in several cases reported in the literature COX-2 inhibitors induced hepatotoxicity. [43][44][45] In our study, we did not observe any change in liver transaminases (alanine aminotransferase and aspartate aminotransferase) and bilirubin after the administration of either the selective COX-2 inhibitor celecoxib or the conventional NSAID naproxen.…”

Section: Discussionmentioning

confidence: 70%

Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites†

et al. 2005

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Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti-inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX-2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis. This investigation consists of a double-blind, randomized, placebo-controlled trial aimed at comparing the effects of the selective COX-2 inhibitor celecoxib (200 mg every 12 hours for a total of 5 doses) on platelet and renal function and the renal response to furosemide (40 mg intravenously) with those of naproxen (500 mg every 12 hours for a total of 5 doses) and placebo in 28 patients with cirrhosis and ascites. A significant reduction (P < .05) in glomerular filtration rate (113 ؎ 27 to 84 ؎ 22 mL/min), renal plasma flow (592 ؎ 158 to 429 ؎ 106 mL/min) and urinary prostaglandin E 2 excretion (3430 ؎ 430 to 2068 ؎ 549 pg/min) and suppression of the diuretic (urine volume: 561 ؎ 128 to 414 ؎ 107 mL/h) and natriuretic (urine sodium: 53 ؎ 13 to 34 ؎ 10 mEq/h) responses to furosemide were observed in the group of patients treated with naproxen but not in the other two groups. Naproxen, but not celecoxib or placebo, significantly inhibited platelet aggregation (72% ؎ 8% to 47% ؎ 8%, P < .05) and thromboxane B 2 production (41 ؎ 12 to 14 ؎ 5 pg/mL, P < .05). In conclusion, our results indicate that short-term administration of celecoxib does not impair platelet and renal function and the response to diuretics in decompensated cirrhosis. Further studies are needed to evaluate the long-term safety of this drug in cirrhosis. (HEPATOLOGY 2005;41:579-587.)

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Acute hepatocellular and cholestatic injury in a patient taking celecoxib

Abstract: A case of acute hepatocellular and cholestatic liver injury that may have been associated with the use of celecoxib is described. This case was reported to US Food and Drug Administration and the manufacturer of celecoxib. (Postgrad Med J 2001;77:548-550)

Cited by 51 publications

References 9 publications

Comparing the Toxic Effects of Nonsteroidal Anti-Inflammatory Drugs (Celecoxib and Ibuprofen) on Heart, Liver, and Kidney in Rats

Comparing the Toxic Effects of Nonsteroidal Anti-Inflammatory Drugs (Celecoxib and Ibuprofen) on Heart, Liver, and Kidney in Rats

Late‐onset celecoxib‐induced combined hepato‐nephrotoxicity

Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites†

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