On July 20, the US Food and Drug Administration (FDA) announced shortages of leucovorin for injection. One manufacturer, Bedford, has not supplied a reason for the shortage or a date when supplies will be available. The other manufacturer, Teva, has cited manufacturing delays and provided an estimated release date in the fourth quarter of 2010.
Levoleucovorin, a related project, is still available. However, the American Society of Health-System Pharmacists (AHSP) cautions that the two agents are not interchangeable, noting the potential dosing errors. The dose for levoleucovorin is 50% of the usual dose of leucovorin. In addition, levoleucovorin is not FDA-approved for oncology indications and may carry a higher price tag.
For some malignancies, substitution of capecitabine for the combination of 5-fluorouracil (5-FU)/leucovorin is supported based on high-quality randomized clinical trials, according to an American Society of Clinical Oncology (ASCO) press release. However, the release noted that such data are not available for all 5-FU/leucovorin-containing regimens. Also of consideration, the side effect profile of capecitabine differs from that of 5-FU/leucovorin (eg, more hand-foot syndrome) as does gastrointestinal absorption.
- Capecitabine has been found to be noninferior to intravenous (IV) FU/leucovorin as single agents for both metastatic colorectal cancer and adjuvant therapy for stage III colon cancer.
- The combination of capecitabine and oxaliplatin was found to be noninferior to IV 5-FU/leucovorin and oxaliplatin (FOLFOX).
- Capecitabine and irinotecan (CAPIRI) was less efficacious and more toxic compared with IV 5-FU/leucovorin and irinotecan (FOLFIRI) at the doses of CAPIRI used in the BICC-C Study.
- No efficacy data are available from two trials testing capecitabine with oxaliplatin in the adjuvant therapy setting for colon cancer to date.
Products affected
Leucovorin calcium lyophilized powder for injection:
· 200 mg vial, 1 count (Bedford)
· 200 mg Novaplus vial, 1 count (Bedford)
· 100 mg vial, 1 count (Teva)
· 350 mg vial, 1 count (Teva)