VISTOGARD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VISTOGARD (VISTOGARD).
Uridine triacetate is a prodrug of uridine, which competes with fluorouracil (5-FU) catabolites for binding to orotate phosphoribosyltransferase, reducing the incorporation of 5-FU metabolites into RNA and DNA, thereby preventing cell death.
| Metabolism | Uridine triacetate is rapidly metabolized by plasma and tissue esterases to uridine. |
| Excretion | Vistogard (uridine triacetate) is primarily excreted via the kidneys as inactive metabolites, with approximately 90% of the administered dose recovered in urine within 24 hours. The remainder is eliminated via feces (about 10%). |
| Half-life | The terminal elimination half-life of uridine triacetate metabolites (primarily uridine and its metabolites) is approximately 2-3 hours. This short half-life supports the need for multiple daily doses (typically 10 doses over 5 days) to maintain therapeutic uridine concentrations. |
| Protein binding | Uridine triacetate is rapidly deacetylated to uridine. Uridine has minimal protein binding (less than 5%), and binding proteins are not clinically significant. |
| Volume of Distribution | The apparent volume of distribution (Vd) of uridine after administration of uridine triacetate is approximately 0.4-0.6 L/kg, indicating distribution primarily into total body water with some tissue penetration. |
| Bioavailability | Bioavailability: 100% after oral administration as uridine triacetate is a prodrug that is completely absorbed and converted to uridine. The oral bioavailability of uridine from uridine triacetate is high (>90%) due to extensive intestinal and hepatic deacetylation. |
| Onset of Action | Oral administration: Therapeutic plasma uridine levels are achieved within 1-2 hours after the first dose. Clinical effect (protection against fluorouracil toxicity) is expected to begin within the first few hours, though the primary benefit is prevention of severe toxicity when given within 96 hours of fluorouracil overdose. |
| Duration of Action | The duration of action is approximately 4-6 hours per dose, based on the time that plasma uridine concentrations remain above the threshold needed to competitively inhibit fluorouracil incorporation into RNA. The full treatment course (10 doses over 5 days) is required for adequate protection. |
6 g (2 vials) intravenously over 15 minutes as a single dose.
| Dosage form | GRANULE |
| Renal impairment | No adjustment required. Vistogard is a uridine triacetate prodrug with renal excretion of metabolites; however, no dose modification based on GFR is recommended in the prescribing information. |
| Liver impairment | No adjustment required for hepatic impairment. No studies in Child-Pugh classes; caution in severe impairment per clinical judgment. |
| Pediatric use | Weight-based dosing: 6.2 g/m² (maximum 6 g) intravenously over 15 minutes as a single dose. |
| Geriatric use | No specific geriatric dose adjustments; use with caution due to potential comorbidities and polypharmacy, but no age-related pharmacokinetic changes reported. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VISTOGARD (VISTOGARD).
| Breastfeeding | It is unknown whether uridine triacetate or its metabolites are excreted in human milk. The molecular weight (438.39 g/mol) suggests potential excretion. Due to lack of data, caution is advised. M/P ratio is not available. |
| Teratogenic Risk | Vistogard (uridine triacetate) is not expected to increase the risk of major birth defects or miscarriage based on its mechanism of action and animal studies. In reproductive studies in pregnant rats and rabbits, doses up to 10 times the human equivalent dose showed no evidence of fetal harm. However, no adequate human studies exist. Use during pregnancy only if clearly needed. |
■ FDA Black Box Warning
None.
| Serious Effects |
["None."]
| Precautions | ["Not effective for toxicity occurring more than 96 hours after fluorouracil/capecitabine administration.","Must be administered as soon as possible after overdose or severe toxicity.","May cause false-positive results in urinary 5-HIAA tests."] |
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| Fetal Monitoring | Monitor for signs of maternal hypersensitivity reactions, including rash, urticaria, and angioedema. Fetal monitoring is not specifically required, but standard obstetric monitoring should be considered. |
| Fertility Effects | In animal studies, uridine triacetate did not impair fertility in male or female rats at doses up to 2000 mg/kg/day (approximately 10 times the human dose). No human data are available. |