Hepatic failure/hepatotoxicity

All azole antifungals carry the potential for rash, photosensitivity, and hepatotoxicity. In general, hepatotoxicity is mild and reversible, presenting as asymptomatic increases in liver transaminases. However, fulminant hepatic failure has been reported with itraconazole. Therefore, serial monitoring of liver function... 

Soni MG, Mehendale HM. 1993. Hepatic failure leads to lethality of chlordecone-amplified hepatotoxicity of carbon tetrachloride. Fund Appl Toxicol 21 442-450. 

Hepatic function impairment Hepatotoxicity and severe hepatic failure occurred in chronic alcoholics following therapeutic doses. Caution chronic alcoholics to limit acetaminophen intake to 2 g/day or less. 

Hepatic function impairment Doses more than 2 g/day IV can be extremely dangerous. In the presence of renal dysfunction, and particularly in pregnancy, IV tetracycline more than 2 g/day has been associated with death secondary to liver failure. Hepatotoxicity has been reported with minocycline. Administer with caution reduce the recommended dosage and/or extend the dosing interval. 

Rare cases of hepatic failure, some leading to death or liver transplant, have occurred with the use of terbinafine for the treatment of onychomycosis in individuals with and without pre-existing liver disease. In the majority of liver cases reported in association with terbinafine use, the patients had serious underlying systemic conditions and an uncertain causal relationship with terbinafine. Terbinafine is not recommended for patients with chronic or active liver disease. Before prescribing terbinafine, assess pre-existing liver disease. Hepatotoxicity may occur in patients with and without preexisting liver disease. Pretreatment serum transaminase (ALT and AST) tests are advised for all patients before taking terbinafine. 

Severe, life-threatening, and, in some cases, fatal hepatotoxicity, including fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure, has been reported in patients treated with nevirapine (see Warnings). 

Hepatotoxicity (e.g., jaundice, hepatitis, hepatic failure, acute renal failure) has been observed in severely ill patients. 

Although it is estimated that 1 in 118,000 patients dies from non-dose-related hepatic failure, no cases have occurred in patients older than 10 years who were receiving valproate monotherapy. Nonetheless, baseline liver function tests are indicated. If baseline test results are normal, monitoring for clinical signs of hepatotoxic-ity is more important than routine monitoring of liver enzyme levels, which has little predictive value and may be less effective than clinical monitoring (Pellock and WiUmore 1991). 

Serious hepatotoxicity is possibie but rare. Hepatic failure occurs in only one in 40,000 cases and appears to be an idiosyncratic reaction that is not dose-related. Children under the age of 2, especially those receiving anticonvulsant polypharmacy, with mental retardation, and/or with poor nutritional status have been shown to be at greatest risk (351, 352). To our knowledge, no cases of hepatic failure have been reported in adults with bipolar disorder who were receiving VPA monotherapy, but liver failure has been reported in older children and in a mentally retarded adult with epilepsy taking VPA alone ( 77, 352, 353). 

SERT. However, trazodone has rarely been associated with inducing priapism. The effects of both nefazodone and trazodone since tx-blocking agents result in a dose-related orthostatic hypotension in some patients. Nefazodone has been associated with hepatotoxicity, including rare fatalities and cases of fulminant hepatic failure requiring transplantation. The rate of serious hepatoxicity with nefazodone has been estimated at 1 in 250,000 to 1 in 300,000 patient-years of nefazodone treatment. 

Hepatic failure associated with tacrine occurred outside the usual time of onset (within 9 months) and resulted in the death of a 75-year-old woman with Alzheimer s disease who had taken tacrine for 14 months (4). Thus, the potential for delayed, life-threatening hepatotoxicity with tacrine, although unusual, should not be overlooked. 

Reversible hepatotoxicity occurred in three children taking lamotrigine (41). In one there was severe hepatic failure. The liver abnormalities resolved after withdrawal. 

Boudreaux JP, Hayes DH, Mizrahi S, Hussey J, Regenstein F, Balart L. Fulminant hepatic failure, hepatorenal syndrome, and necrotizing pancreatitis after minocycline hepatotoxicity. Transplant Proc 1993 25(2) 1873. 

Severe hepatotoxicity has been attributed to thalidomide in multiple myeloma (75) and hepatic failure can occur (21,76,77). 

The same types of liver disease occur with co-trimox-azole as with sulfonamides alone (109-111). Mild rises in serum transaminases and cholestatic hepatotoxicity are well reported, usually starting after a latent period of several weeks, and associated with a rash. There have been very few case reports of fulminant hepatic failure associated with co-trimoxazole. 

A large body of evidence is available examining the acute toxicity of acetaminophen in animal models. Mice and rats have been widely used to study the toxic effects of acetaminophen. Since the rat is relatively resistant, the mouse has been the most widely used species to study both the mechanisms of acetaminophen toxicity and to examine chemicals that potentiate or protect from the toxicity. Hepatotoxic-ity and nephrotoxicity are the two main effects associated with acute overdose of acetaminophen. Of these, death in most species is due to acute hepatic failure. LD50 values range from 350 to 4500mgkg depending on the species and the route of acetaminophen administration, mice (LD50 350-... 

Hepatotoxicity is a concern. During the first few months of therapy, transient elevation of hepatic transaminases occurs in an average 11% (up to 40%) of patients. Fulminant hepatic failure will develop in 1 in 5000-10000 patients. In these cases there is hepatic necrosis, steatosis, and a Reye s syndromelike illness. Fatal hepatic injury is most likely in children less than 2 years old and in those patients on multiple-drug therapy. 

Pemoline. Pemoline (9), an agent used in treatment of ADHD, has been associated with hepatotoxicity, with the majority of cases occurring in pediatric patients. From its marketing in 1975 up to 1989, 12 cases of acute hepatic failure and six deaths associated with pemoline hepatotoxicity had been reported to the FDA (36). Death generally oc-... 

A person s use of alternative medicine must be solicited. Many herbal remedies were once wisely abandoned because of their common adverse reactions. Comfrey tea is a common cause of hepatocellular damage. As in the case of the Chinese remedy jin bu huan, or as in the case of the more elegantly presented chaparral capsules containing grease wood leaves, the end of therapy with these types of agents is occasionally severe disability or death from fulminant hepatic failure." Pennyroyal oil, maragosa oil, and clove oil cause a dose-related hepatotoxicity." ... 

Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives. Children less than 2 years of age are at considerable increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. 

The most common serious side effects are hepatotoxicity, manifested as elevated serum transaminases and hyperglycemia Both regular (crystalline) niacin and sustained-release niacin have been reported to cause severe liver toxicity, and sustained-release niacin can cause fulminant hepatic failure. An extended-release niacin (NIASPAN), appears to be less likely to cause severe hepatotoxicity, perhaps because it is administered only once daily. The incidence of flushing and pruritus with this preparation is not substantially different from that with regular niacin. Severe hepatotoxicity is more likely to occur when patients take >2 g of sustained-release, over-the-counter preparations. Affected patients experience flu-like fatigue and weakness. Usually, serum transaminases are elevated serum albumin levels decline, and total cholesterol and LDL-C levels decline substantially. 

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