Elevated liver enzymes

Isotretinoin Capsules 10, 20, 40 mg 0.5-1 mg/kg/per day in two divided doses Maximum dose 2 mg/kg per day Cumulative dose 120-150 mg/day Dry skin and mucous membranes, muscle and joint pain, elevated liver enzymes and triglycerides, depression, teratogenicity... 

Patient Presents with Elevated Liver Enzymes... 

There are no known health effects such as elevated liver enzymes that are uniquely associated with exposure to 1,4-dichlorobenzene. Therefore, the identification of specific health effects and the development of analytical methods to determine biomarkers of effect for 1,4-dichlorobenzene would be useful. 

Phase I evaluation of CP-724714 in cancer patients is ongoing [68]. The majority of patients in this trial have breast cancer and have received trastuzumab previously. The MTD was determined to be 250 mg with the dose-hmiting toxicity defined as hyperbilirubinemia and elevated liver enzymes. No objective responses have been reported for the 20 patients evaluated to date. Thirty-five percent of patients have experienced stable disease for an imdetermined period of time. In contrast to trastuzumab, cardiomyopathy has not been observed in this trial. 

Hepatotoxicity Available clinical data show no evidence of pioglitazone- and rosiglitazone-induced hepatotoxicity or ALT elevations. It is recommended that patients undergo periodic monitoring of liver enzymes. Check liver enzymes prior to the initiation of therapy in all treated patients. Do not initiate therapy in patients with increased baseline liver enzyme levels (ALT more than 2.5 times the ULN). In patients with normal baseline liver enzymes, it is recommended that liver enzymes be monitored every 2 months for the first 12 months and periodically thereafter. Evaluate patients with mildly elevated liver enzymes (ALT levels less than or equal to 2.5 times the ULN) at baseline or during therapy to determine the cause of the liver enzyme elevation. Proceed with caution in the initiation of, or continuation of, therapy in patients with mild liver enzyme elevations and include appropriate close clinical follow-up, including more frequent liver enzyme monitoring, to determine if the liver enzyme elevations resolve or worsen. If at any time ALT levels increase to more than 3 times the ULN, recheck liver enzyme levels as soon as possible. If ALT levels remain more than 3 times the ULN, discontinue therapy. 

Hepatic - Elevated liver enzymes (piroxicam, mefenamic acid). 

Dose-related adverse reactions Because the frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related, weigh the benefit of improved therapeutic effect with higher doses against the possibility of a greater incidence of adverse reactions. The probability of... 

Efavirenz (Sustiva) is approved for the therapy of HIV infection of adults and children and is also used for postexposure prophylaxis. It is the only NNRTI approved for once-daUy dosing. Rash, although rarely severe, is a common adverse effect of efavirenz. Elevated liver enzymes and serum cholesterol also may occur. Central nervous system (CNS) effects in approximately half of patients may include dizziness, headache, insomnia, drowsiness, euphoria, agitation, impaired cognition, nightmares, vivid dreams, and hallucinations. These effects often subside after several weeks to months of therapy. 

Nevirapine (Viramune) is approved for the treatment of HIV infection in adults and children as part of a combination therapy. During the first 12 weeks of treatment, patients must be closely monitored for the development of potentially fatal hepatic toxicity (i.e., hepatitis, hepatic necrosis, and hepatic failure) and skin reactions (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions). Although these toxici-ties are rare, common side effects include mild to moderate rash, fever, nausea, fatigue, headache, and elevated liver enzymes. 

Thalidomide would fall into this category due to its inadequate testing but most commonly improper use refers to off-label use. Use of off-label pediatric medicines has been discussed earlier in this chapter. An example of off-label adult use is with Bromfenac (Duract), a nonsteroid anti-inflammatory drug. Duract was developed for short term therapy (<10 days) in 1997 butwith longer term, off-label, use elevated liver enzymes were evident and it was withdrawn approximately 1 year later. In its time on the market Duract generated approximately 90 million dollars in sales. 

Adverse effects include nausea, vomiting, diarrhoea, abdominal discomfort, dry mouth, taste disturbances headache, dizziness, insomnia myalgia, rash, pruritus, dry skin, hyperpigmentation, nephrolithiasis, dysuria, haematuria, crystalluria, proteinuria elevated liver enzymes and bilirubin, hepatitis neutropenia, haemolytic anaemia and hyperglycaemia etc. 

Adverse Reactions Hypoglycemia Gastrointestinal disturbances (nausea, diarrhea, constipation, gastralgia) Dermatologic reactions (erythema, morbilliform or maculopapular eruptions, urticaria, pruritus, and eczema) Hematologic reactions (leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia) Metabolic reactions (hepatic porphyria, disulfiram-like reactions) Hyponatremia Elevated liver enzymes... 

Some of the SN/AEMS incidents involved creatine monohydrate that was mixed with or taken with other supplements and substances, so it is difficult to determine to what extent creatine played a role in these reactions. There have also been anecdotal case reports of hypertension (high blood pressure) and elevated liver enzymes in athletes taking creatine supplements. 

Caspofungin is extremely well tolerated, with minor gastrointestinal side effects and flushing reported infrequently. Elevated liver enzymes have been noted in several patients receiving caspofungin in combination with cyclosporine, and this combination should be avoided. 

In this study, the first subject had reported levels of 3% normal factor VIII activity. However, elevated liver enzymes in this subject resulted in temporary suspension of the trial, which was then allowed to resume at lower vector dosages. This trial was prematurely terminated in early 2003 due to a lack of recruited subjects (Kelley et al 2002 High, 2003). 

Heparin is associated with an increased risk of bleeding either due to over anticoagulation or the occurrence of heparin inducted thrombocytopenia. The risk of major bleeding associated with heparin is reported to be 0% to 7% (7,8). The long-term administration of UFH may also be associated with osteopenia, Other reported adverse effects include skin lesions, priaprism, and elevated liver enzymes,... 

Troglitazone, the first clinically available thiazolidinedione, was approved for use in patients who have failed diet therapy and, in combination with insulin and/or sulfonylureas, in patients inadequately controlled with these agents alone (117). Although studies have documented the hypoglycemic efficacy of troglitazone in patients with type 2 diabetes, its use was associated with elevated liver enzymes, liver damage, and death... 

HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). 

Fig. 8 Patient with hypertensive encephalopathy secondary to eclampsia with the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, (a) A T2-weighted MRl showing the extensive cerebral edema in the posterior white matter regions with less involvement of the gray matter, (b) Diffusion-weighted images with only one small area of involvement. The lack of DWl changes is consistent with this being a vasogenic type of edema, and the patient had a good recovery without residual...

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