Dose:   5 to 6 mg/kg/dose IV (see comments)    

Frequency:     Q 12 hours  

Comments:  Ganciclovir is currently the only medication under evaluation for the treatment of CMV in the newborn. Ganciclovir is preferentially absorbed by CMV infected cells and activated by a protein kisase of CMV. Because of significant potential toxicities, ganciclovir should be considered for treatment in symptomatic infants after consultation with the family discussing the risks and benefits of the therapy. Two groups of infants have been evaluated for treatment. The first are micropremature infants who have acquired CMV disease. These infants usually present with pneumonia. Currently ganciclovir is of no proven benefit, though under life-threatening circumstances, a dose of 5 to 6 mg/kg administered IV every 8 hours has been tried (Whitley and Kimberlin. Clin Perinatol 1997; 24:267). The second group of infants are those born with congenital CMV infections. One study has evaluated 50 infants with severe symptomatic congenital CMV infection with CNS disease. The study suggested that the pharmacokinetics of the drug were similar in infants when adjusted for renal function and body surface area. Clinical and laboratory data suggested that therapy improved hearing and growth and produced normalization of liver enzymes and bone-marrow parameters (Whitley. J Infect Dis 1997; 1075:180-186). A follow up study of parenterally administered ganciclovir (6 mg/kg Q 12 hours for 6 weeks) was reported by Kimberlin (J Pediatr 2003; 143:16-25). One hundred infants with symptomatic CMV (infants had microcephaly, intracranial calcification, abnormal CSF, chorioretinitis, and/or hearing deficits) were randomized to receive either 6 weeks of parenteral therapy or no treatment. At 6 months follow up, the ganciclovir-treated infants had no deterioration in hearing compared to 41% of untreated infants. At 12 months follow up, 21% of the ganciclovir-treated infants had a deterioration in hearing at baseline compared to 68% of the untreated infants. Though the reported effects on hearing were significant, the authors noted that of the 100 infants enrolled, 58 were lost to follow up. In addition, overall developmental outcomes were not assessed. And finally, almost two thirds of the treated infants had significant neutropenia. Current trials are now being reported using an oral form (valganciclovir) in combination with ganciclovir.

Toxicity: Ganciclovir has been shown to produce granulocytopenia, thrombocytopenia, and anemia. Kimberlin (J Pediatr 2003; 143:16-25) reported that granulocytopenia was severe enough to require dosage modifications in 14 infants, use of GCSF in two infants, and the development of gram negative sepsis in one infant of 29 infants treated for 6 weeks with ganciclovir.  Its impact on long-term developmental outcomes is unknown.  In animal studies, ganciclovir was shown to be carcinogenic and teratogenic as well as having long-term gonadal toxicity. Ganciclovir increases the toxicity of nephrotoxic and cytotoxic drugs (Facts and Comparisons, Inc. Drug Facts and Comparisons. Olin, B.R. ed. St. Louis, MO:Facts and Comparisons, Inc; 1997, page 407c).

Preparation: Ganciclovir is available as lyphilized powder, 500 mg/10 ml vials. Reconstitute using 10 ml sterile water for injection. Stable for 12 hours at room temperature. Do not refrigerate. Dilute with normal saline, D5W, or LR to 10 mg/ml. Ganciclovir is extremely alkaline (pH=11), avoid contact with skin and mucus membranes. Infuse over 1 hour.

Compatibility: No information available concerning TPN or filters.  Assume to be incompatible with TPN and other medications except those listed above for dilution.