Included as part of the PRECAUTIONS section.

Serious Allergic Reactions

Serious allergic reactions occurred in less than 1% of patients [see ADVERSE REACTIONS].

Monitoring Methotrexate Concentration/Interference with Assay

Methotrexate concentrations within 48 hours following administration of VORAXAZE can only be reliably measured by a chromatographic method. DAMPA (4-deoxy-4-amino-N10- methylpteroic acid) is an inactive metabolite of methotrexate resulting from treatment with VORAXAZE. DAMPA interferes with the measurement of methotrexate concentration using immunoassays resulting in an erroneous measurement which overestimates the methotrexate concentration. Due to the long half-life of DAMPA (t½ of approximately 9 hours), measurement of methotrexate using immunoassays is unreliable for samples collected within 48 hours following VORAXAZE administration [see CLINICAL PHARMACOLOGY].

Continuation and Timing of Leucovorin Rescue

Continue to administer leucovorin after VORAXAZE. Do not administer leucovorin within 2 hours before or after a dose of VORAXAZE because leucovorin is a substrate for VORAXAZE [see DRUG INTERACTIONS].

For the first 48 hours after VORAXAZE, administer the same leucovorin dose as given prior to VORAXAZE. Beyond 48 hours after VORAXAZE, administer leucovorin based on the measured methotrexate concentration. Do not discontinue therapy with leucovorin based on the determination of a single methotrexate concentration below the leucovorin treatment threshold. Therapy with leucovorin should be continued until the methotrexate concentration has been maintained below the leucovorin treatment threshold for a minimum of 3 days.

Continue hydration and alkalinization of the urine as indicated.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

VORAXAZE has not been evaluated in animals for carcinogenic or mutagenic potential or for impairment of fertility.

Use In Specific Populations

Pregnancy

Pregnancy category C

There are no adequate and well controlled studies with VORAXAZE in pregnant women and animal reproduction studies have not been conducted with VORAXAZE. Therefore, it is not known whether VORAXAZE can cause fetal harm when administered to a pregnant woman. VORAXAZE should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known if VORAXAZE is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when VORAXAZE is administered to a nursing woman.

Pediatric Use

The effectiveness of VORAXAZE in pediatric patients was established in Study 1. Of the 22 patients in the efficacy dataset in Study 1, 12 were pediatric patients with ages ranging from 5 to 16 years. Three of the six pediatric patients with a pre-VORAXAZE methotrexate concentration of 1-50 μmol/L achieved a rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, while none of the six pediatric patients with a pre-VORAXAZE methotrexate concentration > 50 μmol/L achieved a RSCIR [see Clinical Studies].

The pooled clinical safety database for VORAXAZE included data for 147 patients from 1 month up to 17 years of age. No overall differences in safety were observed between these patients and adult patients.

Geriatric Use

Of the total number of 290 patients in clinical studies of VORAXAZE, 15% were 65 and over, while 4% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Renal Impairment

No dose adjustment of VORAXAZE is recommended for patients with renal impairment [see CLINICAL PHARMACOLOGY].

Hepatic Impairment

No specific studies of VORAXAZE in patients with hepatic impairment have been conducted.

Last reviewed on RxList: 4/15/2013
This monograph has been modified to include the generic and brand name in many instances.