Toxic hyperbilirubinemia

A second series of reports in the literature purport to discuss the toxicity of phenol to newborns. These, however, deal with an excessive level of hyperbilirubinemia, or jaundice, in newborns in hospital nurseries where a phenolic disinfectant detergent was used to clean the nursery and its equipment (bassinets and mattresses) (Doan et al. 1979, Wysowski et al. 1978). Review of these reports indicated that the detergent did not contain phenol per se. rather it contained more complex phenolics such as o-benzyl-p-chlorophenol and p-tertiary amylphenol. 

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. 

Hepatic Hepatic cholestasis, hepatic toxicity, hepatitis, hyperbilirubinemia, increased liver enzymes, jaundice, liver failure. 

Unauthorized use of these diuretics, or the failure to follow label indications for approved use in the cattle, could lead to unacceptable residues in meat and milk destined for human consumption. While there are no official tolerances for these drugs in milk, the Food and Drug Administration (FDA) has established safe levels that range from 7 ppb for trichlormethiazide, to 10 ppb for furosemide, and 67 ppb for the other thiazides (56). Administration of diuretics is associated with potential toxic effects such as bone marrow depression, hyperbilirubinemia. 

Prevention alone is often not enough. Children still become jaundiced even after careful assessment. When this occurs.it is important to assess the risk of developing significant hyperbilirubinemia. The main concern is that the child will develop acute bilirubin encephalopathy, which is caused by the toxicity of bilirubin on the basal ganglia and other brain stem nuclei. There are early, middle, and late stages of acute bilirubin encephalopathy (Table 22-3). The term kernicterus is applied to chronic... 

Menadione and its water-soluble derivatives are potentially toxic in excess and have been reported to cause hemolytic anemia, hyperbilirubinemia, central nervous system toxicity, and methemoglobinemia in the newborn. 

Significant neonatal morbidity can occur after transabdominal infusion of methylthioninium chloride to diagnose premature rupture of fetal membranes, to stain the amniotic fluid in twin pregnancies, or after postpartum administration of methylthioninium chloride. Toxic manifestations include hyperbilirubinemia, Heinz body hemolytic anemia, and possible desquamation of the skin. In most cases it appears that toxicity was the result of an overdose of methylthioninium chloride (6-9). 

Ribavirin accnmnlates in erythrocytes, resnlting in hemolysis by an nnknown mechanism, perhaps related to oxidative damage to the erythrocyte membrane. Time-dependent and dose-dependent hemolytic anemia (eventnaUy associated with hyperbilirubinemia and a high reticnlocyte connt) is the only major toxic effect associated with oral or intravenons ribavirin and is reversible on withdrawal. There was a fall in hemoglobin concentrations below 10.0 g/dl in 9% of patients with hepatitis C treated with ribavirin and interferon alfa (6,7). 

In 21 patients with squamous cell carcinomas of the head and neck randomized to tretinoin 45, 50, or 150 mg/ m either once daily or as divided doses every 8 hours for 1 year, severe adverse effects included headache in five patients, hypertriglyceridemia in six, mucositis in two, and hyperbilirubinemia, raised alkaline phosphatase, colitis, raised lipase, xerostomia, eczema, and arthritis in one patient each (9). The dose had to be reduced in seven of eight patients with severe toxicity at 90 mg/m / day. Three of nine patients taking 45 mg/m /day required dose reductions. The plasma AUC of tretinoin did not correlate with the severity or frequency of adverse effects. From these results it can be concluded that 15 mg/m /day every 8 hours is a tolerable dose for 1 year in patients with squamous cell carcinomas of the head and neck. 

Indomethacin is FDA approved for closure of persistent patent ductus arteriosus. Successful closure is obtained in >70% of neonates treated with the drug. Such therapy is indicated primarily in premature infants who weigh between 500 and 1750 g, who have a hemodynamically significant patent ductus arteriosus, and in whom other supportive maneuvers have been attempted. Unexpectedly, treatment with indomethacin also may decrease the incidence and severity of intraventricular hemorrhage in low-birth-weight neonates. The principal limitation of treating neonates is renal toxicity, and therapy is stopped if urine output falls to <0.6 mL/kg/h. Renal failure, enterocolitis, thrombocytopenia, or hyperbilirubinemia are contraindications to the use of indomethacin. 

Toxicity Nausea, diarrhea, thrombocytopenia, hyperbilirubinemia, and nephrolithiasis occur. To reduce renal damage, it is important to maintain good hydration. Indinavir is a substrate for and an inhibitor of the cytochrome P450 isoform CYP3A4 and is implicated in drug interactions. Serum levels of indinavir are increased by azole antifungals and decreased by rifamycins. Indinavir increases the serum levels of antihistamines, benzodiazepines, and rifampin. 

The toxicity associated with excessive amounts of vitamin K in humans has not been unequivocally defined, although it has been suggested that excessive doses of one of its forms, menadione, can contribute to the occurrence of hemolytic anemia, jaundice, kemicterus, and hyperbilirubinemia (Worthington-Roberts, 1988). 

Diarrhea is a dose-limiting adverse reaction to uracil-ftorafur. However, it is less toxic than bolus fluorouracil and causes significantly less myelosuppression and mucositis [108 , 109 "]. Other common adverse reactions include nausea, vomiting, fatigue, and hyperbilirubinemia. Hand-foot syndrome is very rare. 

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