Upper limit of normal

MMI and PTU can lead to methimazole embryopathy with choanal or esophageal atresia. In pregnant women the antithyroid diug dose should be minimized to prevent fetal hypothyroidism by maintaining the maternal free thyroxine serum level slightly above the upper limit of normal. 

The serum amylase can be elevated three times the upper limit of normal within the first 12 hours of the onset of acute pancreatitis. The degree of elevation does not predict the severity of disease. 

Factors associated with a higher likelihood of response to interferon therapy are baseline HBV DNA levels less than 200 pg/mL and ALT concentrations greater than 5 times the upper limit of normal.29... 

A few cases of hepatotoxicity have been reported with rosiglitazone and pioglitazone, but no serious complications have been reported, and symptoms typically reverse within several weeks of discontinuing therapy. Therefore, periodic liver function tests should be performed at baseline and during thiazolidinedione therapy. Patients with a baseline alanine aminotransferase (ALT) level greater than 2.5 times the upper limit of normal should not receive a TZD. If ALT levels rise to greater than 3 times the upper limit of normal in patients receiving a TZD, the medication should be discontinued. 

Elevated hepatic transaminases (greater than 5 times upper limit of normal) or bilirubin (greater than 2.5 upper limit of normal)... 

TC, lamivudine ABC, abacavir APV, amprenavir AST, aspartate aminotransferase ALT, alanine aminotransferase ATV, atazanavir CBC, complete blood cell count D/C, discontinue ddl, didano-sine d4T, stavudine EFV, efavirenz FTC, emtricitabine P1BV, hepatitis B virus F1CV, hepatitis C vims HIV, human immunodeficiency virus IDV, indinavir IV, intravenous LFT, liver function tests LPV/r, lopinavir + ritonavir NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor PT, prothrombin time T.bili, total bilirubin TDF, tenofovir disoproxiI fumarate TPV, tipranavir ULN, upper limit of normal ZDV, zidovudine. 

Liver tests less than 2-3 times upper limit of normal... 

Several case reports of hepatotoxicity with pioglitazone or rosiglitazone have been reported, but improvement in alanine aminotransferase (ALT) was consistently observed upon drug discontinuation. Baseline ALT should be obtained prior to therapy and then periodically thereafter at the practitioner s discretion. Neither drug should be started if the baseline ALT exceeds 2.5 times the upper limit of normal. The drugs should be discontinued if the ALT is more than 3 times the upper limit of normal. 

The serum amylase concentration usually rises 4 to 8 hours after symptom onset, peaks at 24 hours, and returns to normal over the next 8 to 14 days. Serum amylase concentrations greater than three times the upper limit of normal are highly suggestive of AP. 

Patients should have blood urea nitrogen, serum creatinine, aspartate transaminase or alanine transaminase, and a complete blood count determined at baseline and periodically, depending on the presence of other factors that may increase the likelihood of toxicity (advanced age, alcohol abuse, and possibly pregnancy). Hepatotoxicity should be suspected in patients whose transaminases exceed five times the upper limit of normal or whose total bilirubin exceeds 3 mg/dL. At this point, the offending agent(s) should be discontinued, and alternatives selected. 

The starting and recommended dose of tolcapone is 100 mg three times daily as an adjunct to carbidopa/L-dopa. Its use is limited by the potential for fatal liver toxicity. Strict monitoring of liver function is required, and tolcapone should be discontinued if liver function tests are above the upper limit of normal or any signs or symptoms suggestive of hepatic failure exist. It should be reserved for patients with fluctuations that have not responded to other therapies. 

Liver function test abnormalities are common. If aminotransferases are greater than three times the upper limit of normal, the antipsychotic should be changed to a chemically unrelated antipsychotic. These changes are less common with the SGAs but are reported with risperidone and clozapine. 

The search for more potent, selective and safe PPARa agonists has been challenging and only a limited number of compounds have progressed into the clinic. A number of phenoxyacetic acid derivatives and other diverse structures have emerged recently. Oral administration of LY-518674 (6) produced a 208% elevation in HDL and a 96% decrease in serum TG in apoA-I transgenic mice [38,39]. Recent clinical studies with compound 6 revealed a decrease in TG and an increase in HDL similar to fenofibrate. However, compound 6 also raised LDL-C in a dose-dependent fashion, and to a much higher level than seen with fenofibrate [28]. Both agents also raised serum creatinine levels above the upper limits of normal in 35-38% of patients [28]. 

Chronic in vivo hemolysis produces serum lactic dehydrogenase elevations in patients with mitral or atrial valve cardiac prosthesis (J2). In a series of 11 such patients these increases ranged from 1.1 to 1.6 times the upper limit of normal (S29). Blood pH is altered in hemolyzcd specimens because carbonic anhydrase is liberated from the erythrocytes and presumably alters the distribution of H2CO3 and NaHCOs (B2). Hemolysis will effect acid phosphatase activity if the substrate is hydrolyzed by erythrocyte acid phosphatase. Thus, hemolysis would be of concern if phenyl phosphate was the substrate, but would have a negligible effect if )8-glycerophosphate, which is not hydrolyzed by red cell acid phosphatase, was used (Bl). 

Intramuscular injections have been shown to produce elevations in serum enzyme activities presumably due to either inflammatory areas in the muscle or actual breakdown of cells and release of enzyme. In one study, preinjection values of creatine phosphokinase were in the normal range of 24-100 units. Multiple intramuscular injections of penicillin, diuretics, and narcotics every 6 hours caused the creatine phosphokinase values to rise to levels between 160 to 240 units, or up to 2.5 times the upper limit of normal. When the injections were stopped, the creatine phosphokinase values returned to normal within 48 hours (B7). Similar observations of aspartate aminotransferase activities were made in patients receiving intramuscular injections of penicillin every 4 hours. Activities rose to values as high as 200 units. Other workers have reported injection related serum creatine phosphokinase elevations following intramuscular administration of chlorpromazine and suxamethonium (HIO, M11,T6). 

Gl bleeding, posttraumatic bleeding, and perioperative bleeding. The incidence of elevated alkaline phosphatase (more than 2 times upper limit of normal) was 7.6% in ticlopidine patients. The incidence of elevated AST (more than 2 times upper limit of normal) was 3.1% in ticlopidine patients. 

Avoid use of high doses of argatroban in PCI patients with clinically significant hepatic disease or AST/ALT levels at least 3 times the upper limit of normal. Pregnancy Category B. 

Lab test abnormalities Asymptomatic increases in AST and ALT levels greater than 3 times the upper limit of normal of the laboratory reference range have been reported. Such elevations are fully reversible and are rarely associated with increases in bilirubin. 

Elevated serum transaminase /eve/s- Treatment-emergent elevations of serum transaminases (AST and /or ALT) above the upper limit of normal... 

Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking metformin do not necessarily indicate impending lactic acidosis and may be explained by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. 

Renal function impairment Metformin is known to be excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Do not give metformin to patients with serum creatinine levels above the upper limit of normal for their age. 

Therapy with rosiglitazone/glimepiride should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT greater than 2.5 x upper limit of normal at start of therapy). Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with rosiglitazone/glimepiride and periodically thereafter. 

Paget disease of bone For treatment of Paget disease of bone where alkaline phosphatase is at least 2 times the upper limit of normal, or those who are symptomatic or at risk for future complications from their disease (alendronate, risedronate, tiludronate) treatment of symptomatic Paget disease (etidronate) treatment of moderate to severe Paget disease (pamidronate). 

AST elevation and liver injury Elevations of AST more than 3 times the upper limit of normal occurred in about 1% of both mexiletine-treated and control patients. 

Hyperkaiemia Elevated serum potassium (at least 0.5 mEq/L greater than the upper limit of normal) was observed in 0.4% of hypertensive patients given trandolapril, approximately 1% of hypertensive patients given benazepril, enalapril, ramipril, or moexipril approximately 2% of patients receiving quinapril or lisinopril, approximately 2.6% of hypertensive patients given fosinopril, and approximately 4.8% of CHF patients given lisinopril. Hyperkalemia also occurred with captopril. Vaivuiar stenosis Theoretically, patients with aortic stenosis might be at risk of decreased coronary perfusion when treated with vasodilators, because they do not develop as much afterload reduction as others. 

Hepatic function impairment Fenofibrate is associated with significant increases in serum transaminases (AST or ALT). Increases to more than 3 times the upper limit of normal (ULN) occurred. Hepatocellular, chronic active and cholestatic hepatitis associated with fenofibrate therapy have been reported after exposures of weeks to several years. 

Perform liver function tests on all patients during therapy with nicotinic acid. Monitor serum transaminase levels, including ALT and AST, before treatment begins, every 6 to 12 weeks for the first year, and periodically thereafter (at approximately 6-month intervals). Discontinue the drug if the transaminase levels show evidence of progression, particularly if they rise to 3 times the upper limit of normal and are persistent or if they are associated with symptoms of nausea, fever, or malaise. Consider liver biopsy if elevations persist beyond discontinuation. 

Active liver disease or transaminase elevations 3 times or more the upper limit of normal, hypersensitivity to zileuton or any of its inactive ingredients. 

Cholesterol/Triglycerides Nonfasting cholesterol increases to 20% or more above the upper limits of normal and nonfasting triglyceride increases to 500 mg/dL or more were observed. 

Discontinue nefazodone if clinical signs or symptoms suggest liver failure. Patients who develop evidence of hepatocellular injury such as increased serum AST or serum ALT levels at least 3 times the upper limit of normal while on nefazodone should be withdrawn from the drug. These patients should be presumed to be at increased risk for liver injury if nefazodone is reintroduced. Accordingly, do not consider such patients for retreatment. 

Dose adjustment Monitor serum transaminase levels (specifically ALT) every other week from at least week 4 to week 16 following initiation of treatment, after which monitoring may be decreased to every 3 months. For patients who develop ALT elevations more than 2 times the upper limit of normal (ULN), the dose and monitoring regimen should be modified as described in the table below. 

Hepatic function impairment No dose adjustment is necessary in patients with liver function tests less than or equal to 5 times the upper limit of normal. Continued monitoring of liver function tests for further elevations is recommended (see Warnings). 

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