UVADEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UVADEX (UVADEX).
Uvadex, when combined with UVA light, intercalates into DNA and upon UVA activation forms covalent cross-links with pyrimidine bases, thereby inhibiting DNA synthesis and inducing apoptosis in activated T-cells.
| Metabolism | Primarily hepatic via CYP450 enzymes, specifically CYP1A1 and CYP1B1, to form metabolites including 8-methoxypsoralen hydroxylation products. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 70% within 24 hours) and metabolites; minor fecal elimination (<10%). |
| Half-life | Terminal elimination half-life is approximately 12 hours (range 8-20 hours) following intravenous administration; clinically, this supports daily dosing schedules. |
| Protein binding | Approximately 90-95% bound to serum proteins, predominantly albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.15-0.3 L/kg, suggesting limited extravascular distribution and primarily confinement to the vascular compartment. |
| Bioavailability | Intravenous: 100% (administered directly into the circulation via photopheresis). |
| Onset of Action | Intravenous: Onset of photopheresis-induced immune modulation begins within 2-4 hours post-infusion, with peak phototoxic effect during UVA exposure. |
| Duration of Action | Duration of photopheresis effect is approximately 48-72 hours, corresponding to the time required for apoptotic cell clearance and immune modulation; repeated cycles are typically performed on two consecutive days every 2-4 weeks. |
200 mcg/mL solution administered via intravenous injection 0.017 mL/kg (3.4 mcg/kg) 30 minutes prior to each photopheresis treatment, given on two consecutive days every 2–4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based dose adjustments established; use caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation, consider extended dosing interval. |
| Liver impairment | No specific Child-Pugh based adjustments; contraindicated in hepatic disease that precludes photopheresis procedure. Monitor liver function; dose reduction not defined. |
| Pediatric use | Safety and efficacy in pediatric patients not established; no standard weight-based dosing guidelines available. |
| Geriatric use | No specific dose adjustment recommended; start at low end of dosing range due to age-related declines in organ function, monitor for toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for UVADEX (UVADEX).
| Breastfeeding | Methoxsalen is excreted in human milk. The milk-to-plasma (M/P) ratio is not well established, but due to its molecular weight, it is likely to be present in breast milk. Breastfeeding is generally not recommended during therapy and for at least 24 hours after the last dose to minimize infant exposure. Consider alternative feeding methods. |
| Teratogenic Risk | Uvadex (methoxsalen) is a photosensitizing agent used in photopheresis. Based on animal studies, methoxsalen has demonstrated teratogenic effects at doses higher than the therapeutic dose. In the first trimester, there is a potential risk of fetal malformations, particularly of the central nervous system and skeletal system. In the second and third trimesters, risk may include growth retardation and functional deficits. Data in humans are limited, but the drug should be avoided during pregnancy unless clearly necessary. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to methoxsalen or any component","Aphakia (absence of lens) due to increased retinal phototoxicity risk","History of melanoma or other photosensitive skin cancers","Pregnancy and breastfeeding"]
| Precautions | ["Photosensitivity: Severe burns may occur with UVA exposure; avoid sun/bulb light for 24 hours post-treatment.","Hematologic toxicity: Monitor CBC due to risk of myelosuppression.","Pregnancy: Can cause fetal harm; advise contraception.","Carcinogenicity: Psoralen + UVA is carcinogenic in animal studies."] |
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| Fetal Monitoring | Monitor maternal complete blood count, liver function tests, and renal function periodically. Assess for signs of photosensitivity reactions. Fetal monitoring includes ultrasound to assess growth and anatomy, as well as fetal heart rate monitoring if used in later pregnancy. Avoid concurrent phototherapy during pregnancy. |
| Fertility Effects | No specific studies on human fertility are available. In animal studies, high doses of methoxsalen have been associated with impaired fertility and gonadal toxicity. Male and female patients of reproductive potential should use effective contraception during treatment and for a period after discontinuation (at least one menstrual cycle). |