Phenobarbital is a potent inducer of microsomal enzymes that increases bilirubin conjugation and excretion and increases bile flow. When given in sufficient doses to the mother, the infant, or both, phenobarbital is effective in lowering serum bilirubin levels in the first week of life (226,548). However, concerns about long-term toxicity when given to pregnant women militate against its use for this purpose (549,550).

As illustrated in Fig. 35-1, the enzyme microsomal heme oxygenase is necessary for the conversion of heme to biliverdin, one of the first steps in the formation of bilirubin from hemoglobin. Certain synthetic metalloporphyrins are powerful competitive inhibitors of heme oxygenase and suppress the formation of bilirubin. The inhibition of heme degradation to bilirubin does not result in the accumulation of heme; the heme is excreted unchanged in the bile in quantities that compensate for the decreased excretion of bilirubin (226).

In a series of controlled clinical trials in Greece and Argentina, Kappas and colleagues demonstrated that tin mesoporphyrin (SnMP) is a potent inhibitor of heme oxygenase and is highly effective in reducing TSB levels and the requirements for phototherapy in term and preterm
neonates (370,551,552). They also showed that SnMP in a single dose of 6 μmol/kg was more effective than special blue-light phototherapy in the treatment of term and near-term neonates with established hyperbilirubinemia (551,552). SnMP was equally effective in controlling hyperbilirubinemia in infants with G6PD deficiency (553); a U.S. trial of term and near-term infants showed similar results (554). The only side effect seen so far has been a transient, non-dose-dependent erythema that disappeared without sequelae in infants who received (white light) phototherapy after SnMP administration (555). SnMP has been used in the treatment of the Crigler-Najjar syndrome and has achieved a temporary reduction in TSB levels (369,556), and SnMP has prevented the need for exchange transfusion in Jehovah’s Witness newborns with Rh hemolytic disease (557). Kappas reviewed the published controlled clinical trials performed with SnMP (370). Of 279 infants in the control groups, 129 (46%) received phototherapy versus 13 of 443 (3%) of the infants who received SnMP.