New Drug for Treatment of Cytomegalovirus
New Drug for Treatment of Cytomegalovirus
Abstract & Commentary
Synopsis: Valganciclovir, a prodrug of ganciclovir, is effective in the treatment of CMV retinitis after oral administration.
Source: Am J Health Syst Pharm. 2001;58:946, 948.
Roche has obtained approval for the marketing of valganciclovir (Valcyte), an oral prodrug of ganciclovir. Valganciclovir, like intravenous ganciclovir, is indicated for treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Currently, oral ganciclovir is only indicated for maintenance therapy after suitable induction therapy with intravenous ganciclovir. While no comparative clinical data are available on the efficacy of valganciclovir for maintenance therapy of CMV retinitis, the blood levels of ganciclovir following valganciclovir support its use. Compared to the higher recommended doses of oral ganciclovir, a 900-mg dose of valganciclovir produces a similar AUC and a higher Cmax. While both intravenous and oral ganciclovir are indicated for prevention of CMV infection in high-risk solid-organ-transplant recipients, valganciclovir has not yet been evaluated for this indication.
Ingested, valganciclovir is rapidly converted to ganciclovir by esterases in the intestinal wall and liver. The bioavailability of valganciclovir is significantly higher than ganciclovir capsules, and because the bioavailability is increased by a high-fat meal, it should be taken with food. It is eliminated renally as ganciclovir through glomerular filtration and active tubular secretion. The dose must be adjusted in patients with renal dysfuction and it cannot be given to hemodialysis patients because it is not available in a small enough dosage form. Like ganciclovir, patients should be monitored closely for the risks of granulocytopenia, anemia, and thrombocytopenia, and it should not be administered to patients if the absolute neutrophil count is less than 500 cells/µL, the platelet count is less than 25,000/µL, or the hemoglobin is less than 8 g/dL. Because of the teratogenicity of valganciclovir and ganciclovir, the usual cautions regarding pregnancy, breast-feeding, and the need for adequate contraception apply.
In an open-label study that was used to gain approval for the drug, 160 AIDS patients with newly diagnosed CMV retinitis were randomized to receive induction therapy with either oral valganciclovir or intravenous ganciclovir. The dosage of valganciclovir was 900 mg twice daily for 21 days, followed by 900 mg once daily for 7 days. (For comparison, the maintenance dosage of oral ganciclovir is 1000 mg 3 times daily, due to its lower bioavailability.) The dosage of intravenous ganciclovir was 5 mg/kg twice daily for 21 days, followed by 5 mg/kg once daily for 7 days. The progression of retinitis was determined on the basis of masked review of retinal photographs taken at baseline and week 4, and was nearly identical in both groups with approximately 80% of the patients remaining stable. Additionally, all adverse effects such as diarrhea, nausea, headache, vomiting, abdominal pain, pyrexia, insomnia, peripheral neuropathy, parasthesia, and retinal detachment occurred at similar rates between the 2 groups.
The product is available as 450-mg tablets and because of potential toxicities, the tablets are not to be broken or crushed. Complete product information is available at http://rocheusa.com/products/valcyte/pi.html.
Comment by Thomas G. Schleis, MS, RPh
Valganciclovir does appear to offer an advantage over oral ganciclovir in that it can be used as induction therapy in the treatment of CMV retinitis. The other advantage is that it can be administered once daily as maintenance therapy, unlike oral ganciclovir, which must be given 3 times daily. This would be expected to increase compliance in a population that is already burdened with numerous and complex medication regimens.
The comparative costs of intravenous and oral ganciclovir vs. valganciclovir for a 70 kg patient are shown in Tables 1 and 2.
Table 1: Comparative Costs of Intravenous and Oral Ganciclovir vs. Valganciclovir for a 70 kg Patient* | |||
Medication | Therapy | Total
Daily Dosage (70 kg person) |
Total
Daily Average Wholesale Price* |
|
|||
IV Ganciclovir | Treatment of CMV retinitis |
5 mg/kg q 12 h
= 700 mg |
$51.94 |
Oral Ganciclovir | Treatment of CMV retinitis |
N/A | N/A |
Valganciclovir | Treatment of CMV retinitis |
900 mg q 12 h = 1800 mg |
$115.12 |
|
|||
*Based upon MediSpanTM Average Wholesale Pricing of $927.43 for 25 vials of 500 mg ganciclovir for injection, $1541.58 for 180 capsules of oral ganciclovir, and $1726.56 for 60 tablets of valganciclovir. | |||
|
Table 2: Comparative Costs of Intravenous and Oral Ganciclovir vs. Valganciclovir for a 70 kg Patient* | |||
Medication | Therapy | Total
Daily Dosage (70 kg person) |
Total
Daily Average Wholesale Price* |
|
|||
IV Ganciclovir | Maintenance therapy for CMV retinitis |
5 mg/kg q 24 h = 350 mg |
$25.97 |
Oral Ganciclovir | Maintenance therapy for CMV retinitis |
1000 mg 3 times daily = 3000 mg |
$51.36 |
Valganciclovir | Maintenance therapy for CMV retinitis |
900 mg q 24 h | $57.56 |
|
|||
*Based upon MediSpanTM Average Wholesale Pricing of $927.43 for 25 vials of 500 mg ganciclovir for injection, $1541.58 for 180 capsules of oral ganciclovir, and $1726.56 for 60 tablets of valganciclovir. | |||
|
From the cost comparison, it is interesting to note that intravenous ganciclovir is actually the least expensive in terms of drug costs, although the other costs associated with intravenous therapy such as catheters, supplies, and personnel costs would still make it the most expensive therapy. In most cases, however, oral medications are usually less expensive than their intravenous counterparts. For maintenance therapy, the cost of oral ganciclovir and valganciclovir is similar and the advantage of once daily administration makes valganciclovir the obvious choice.
In summary, oral valganciclovir now makes it possible to treat CMV retinitis and provide maintenance therapy without the need for intravenous therapy. The advantage of once daily administration and similar cost makes it the preferred choice for maintenance therapy, although it currently does not have FDA approval for this indication.
Thomas Schleis is Director of Pharmacy Services for Infections Limited in Tacoma, Wa., Section Editor of Managed Care, and Associate Editor of Infectious Disease Alert.
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