Carbamazepine
1
Carbamaze,lne Fat .. fullDlDlDt )a.,atlc Deerosls Two cases are reported. D A 37-year-old woman, with a lO-year history of alcohol abuse, started treatment with carbamazepine 600mg daily, disulfiram 400mg daily and vitamin B tablets. Within 8 days she developed fever, and a generalised maculopapular rash. Although the disulfuram and vitamin B were withdrawn immediately, the fever and exanthema persisted until the 14th day, when carbamazepine was also witbdrawn. The symptoms remitted within 2 days, but a maculopapulous rash develoPed immediately after chlorprothixene (JOmg) was given 4 days later. Although these symptoms disappeared within I day, she developed anorexia, nausea and jaundice a further 2 days later. There was no sign of chronic liver dysfunction and the liver was not palpable. Serum bilirubin (136pmol/L) and gamma glutamyl transferase(S350U/U were markedly higher than pretreatment levels (lOllmol/Land 28U/L. respectively). Prothrombin was 18 % of normal (previously 82 % of normal). No hepatitis B antigens were found, and although small quantities of hepatitis A antibodies were detected, there were no IgM antibodies, which thus precluded a recent history of hepatitis A. Despite oral neomycin and lactulose and IV Ouids, hepatiC coma developed and she died 7 days after the onset of jaundice. D A 23-year-old epileptic had been managed on carbamazepine alone for the previous 4 years, and for the last 9 months had been stabilised on 400mg/day. She became fatigued, nauseous and developed epigastriC pain. Three weeks later she was admitted and jaundice was diagnosed although there was no evidence of alcohol or drug abuse, or exposure to hepatitis. There were no signs of chronic hepatic dysfunction, though the liver was slightly enlarged and tender. Serum bilirubin was 2 391lmol/ L, gamma glutamyl transferase 20SU/Land prothrombin 21 % of normal. Carbamazepine was SUlpectfd, so the drug was immediately withdrawn and the patient given c10nazepam I. Smg daily. Once again, despite neomycin and Jactalose therapy. the patient developed hepatic coma and died 14 days after admission. In both patients autopsy revealed massive liver cell necrosis, with virtual or tDtalloss of intact liver tissue. Some random infiltrates of mononuclear cells and granulocytes were noted. Although the first patient had a history of alcohol abuse there was no indication of alcohol-induced liver damage. Hepatotoxicity has previously been reported in alcoholics after disulfiram therapy and although the fever and rash appeared to be more closely connected to carbamazepine, disulfiram may have enhanced the liver damage by altering carbamazepine metabolism. The second patient received 0157-7271/82/0129-0003/0$00.50/0 CADIS Press only carbamazepine, but the prognosis may have been better if the drug had been withdrawn at the first onset of symptoms. It appears that physicians should be aware of the hepatotoxicity of carbamazepine, and that it should not be given with disulfiram to patients with a possibly already compromised hepatic function. Hopen, G. eta!.: AccaMedicaSc:andi .. vial210, 333 (No 4.1981) Reactions 29 Jan 1982 3
Transcript of Carbamazepine
Carbamaze,lne
Fat .. fullDlDlDt )a.,atlc Deerosls Two cases are reported. D A 37-year-old woman, with a lO-year history of alcohol abuse, started treatment with carbamazepine 600mg daily, disulfiram 400mg daily and vitamin B tablets. Within 8 days she developed fever, and a generalised maculopapular rash. Although the disulfuram and vitamin B were withdrawn immediately, the fever and exanthema persisted until the 14th day, when carbamazepine was also witbdrawn. The symptoms remitted within 2 days, but a maculopapulous rash develoPed immediately after chlorprothixene (JOmg) was given 4 days later. Although these symptoms disappeared within I day, she developed anorexia, nausea and jaundice a further 2 days later. There was no sign of chronic liver dysfunction and the liver was not palpable. Serum bilirubin (136pmol/L) and gamma glutamyl transferase(S350U/U were markedly higher than pretreatment levels (lOllmol/Land 28U/L. respectively). Prothrombin was 18 % of normal (previously 82 % of normal). No hepatitis B antigens were found, and although small quantities of hepatitis A antibodies were detected, there were no IgM antibodies, which thus precluded a recent history of hepatitis A. Despite oral neomycin and lactulose and IV Ouids, hepatiC coma developed and she died 7 days after the onset of jaundice. D A 23-year-old epileptic had been managed on carbamazepine alone for the previous 4 years, and for the last 9 months had been stabilised on 400mg/day. She became fatigued, nauseous and developed epigastriC pain. Three weeks later she was admitted and jaundice was diagnosed although there was no evidence of alcohol or drug abuse, or exposure to hepatitis. There were no signs of chronic hepatic dysfunction, though the liver was slightly enlarged and tender. Serum bilirubin was 2 391lmol/ L, gamma glutamyl transferase 20SU/Land prothrombin 21 % of normal. Carbamazepine was SUlpectfd, so the drug was immediately withdrawn and the patient given c10nazepam I. Smg daily. Once again, despite neomycin and Jactalose therapy. the patient developed hepatic coma and died 14 days after admission. In both patients autopsy revealed massive liver cell necrosis, with virtual or tDtalloss of intact liver tissue. Some random infiltrates of mononuclear cells and granulocytes were noted. Although the first patient had a history of alcohol abuse there was no indication of alcohol-induced liver damage. Hepatotoxicity has previously been reported in alcoholics after disulfiram therapy and although the fever and rash appeared to be more closely connected to carbamazepine, disulfiram may have enhanced the liver damage by altering carbamazepine metabolism. The second patient received
0157-7271/82/0129-0003/0$00.50/0 CADIS Press
only carbamazepine, but the prognosis may have been better if the drug had been withdrawn at the first onset of symptoms. It appears that physicians should be aware of the hepatotoxicity of carbamazepine, and that it should not be given with disulfiram to patients with a possibly already compromised hepatic function. Hopen, G. eta!.: AccaMedicaSc:andi .. vial210, 333 (No 4.1981)
Reactions 29 Jan 1982 3
