Leucovorin calcium is available as a lyophilized powder in preservative-free single-dose vials containing leucovorin 50, 100, 200, 350, and 500 mg as the calcium salt with sodium chloride and sodium hydroxide or hydrochloric acid to adjust the pH.3845; 3846 Reconstitute the vials with bacteriostatic water for injection containing benzyl alcohol or sterile water for injection with the volumes indicated in Table 1.3845; 3846
Table 1. Recommended Reconstitution of Leucovorin Calcium3845; 3846
| Vial Size (mg) | Volume of Diluent (mL) | Concentration (mg/mL) |
|---|---|---|
| 50 | 5 | 10 |
| 100 | 10 | 10 |
| 200 | 20 | 10 |
| 350 | 17.5 | 20 |
| 500 | 50 | 10 |
Diluents containing benzyl alcohol are not recommended when doses greater than 10 mg/m2 are required; for such doses, the drug should be reconstituted with sterile water for injection.3845; 3846
Leucovorin calcium is also available as a 10-mg/mL injection solution in single-dose vials.3847 Each mL of solution contains leucovorin 10 mg as the calcium salt with sodium chloride and hydrochloric acid and/or sodium hydroxide to adjust the pH.3847
pH
Leucovorin calcium injection is administered by intramuscular injection or by intravenous injection or infusion.3845 The infusion rate should not exceed 160 mg/min (e.g., 16 mL of a 10-mg/mL solution or 8 mL of a 20-mg/mL solution per minute) due to the calcium content.3845
Leucovorin calcium should not be administered intrathecally; manufacturers state that leucovorin may be harmful or fatal if given intrathecally.3845; 3846
Leucovorin calcium lyophilized powder in intact vials should be stored at controlled room temperature in the original carton and protected from light.3845
When the lyophilized powder is reconstituted with sterile water for injection, the solution should be used immediately and any unused portion discarded.3845 When reconstituted with bacteriostatic water for injection, the solution may be used for up to 7 days.3845
Intact vials of leucovorin calcium injection should be stored at 2 to 8°C in the original cartons and protected from light.3847 In a study, leucovorin calcium injection (Teva) in the original glass vials stored protected from light at 2 to 8°C or 15 to 25°C and sampled at multiple time points was stable with no loss of drug for up to 30 days after initial entry into the vial; however, over 10% losses in drug concentrations were observed at 34 days at both storage temperatures.3848
pH Effects
Leucovorin calcium solutions exhibit good stability at pH 6.5 to 10. The pH of maximum stability was determined to be 7.1 to 7.4. Below pH 6, increased decomposition occurs.1276
Central Venous Catheter
Leucovorin calcium (Gensia) 2 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.2335
Drugs in Syringe Compatibility
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Fluorouracil
Because of the risk of precipitation, leucovorin calcium should not be mixed in the same infusion as fluorouracil.3845 Although chemical stability and physical compatibility of fluorouracil with leucovorin calcium have been reported,505; 980; 1309; 1387; 1817 more recent work found substantial amounts of subvisual particles in this drug combination over numerous concentrations when stored at 4, 23, and 32°C. Particulate formation sometimes clogged filters and disrupted multiple-day treatment. Particulate formation began in about 24 hours in most samples, and particles were found in all samples within 7 days. Fluorouracil and leucovorin calcium in the same container can no longer be considered a compatible combination.1816
Fluorouracil combined with leucovorin calcium for repeated administration using a Fresenius implanted port resulted in blockage of the pump catheter and necessitated surgical removal of the port. The blockage was caused by precipitation of calcium carbonate in the catheter.2504
For a list of references cited in the text of this monograph, search the monograph titled References.