Folic acid is available as a 5-mg/mL solution for injection in 10-mL multiple-dose vials.3964 Each mL contains the equivalent of folic acid 5 mg (as sodium folate) with edetate disodium 2 mg, benzyl alcohol 15 mg as a preservative, and hydrochloric acid and/or sodium hydroxide to adjust pH in water for injection.3964 Aluminum also is present.3964
pH
From 8 to 11.3964
Aluminum Content
Aluminum content may vary depending on the product; specific product labeling should be consulted.
Folic acid injection (Fresenius Kabi) is stated to contain no more than 3500 mcg of aluminum per L.3964
Folic acid injection is administered by intramuscular, intravenous, or subcutaneous injection.3964
Folic acid injection should be stored at controlled room temperature and protected from light.3964 The manufacturer states vials should be retained in the carton until contents are used.3964
Light Effects
Folic acid injection should be protected from light.3964 However, exposure of folic acid in parenteral nutrition solutions to fluorescent light for 48 hours did not cause any significant loss of folic acid.896
pH Effects
Folic acid is soluble in solutions of pH 5.6 or above at room temperature to a concentration of 1 g/L. However, below about pH 4.5 to 5, folic acid may precipitate in varying time periods, depending on the acidity of the solution. In the small concentrations used for parenteral nutrition, a pH of above 5 ensures that folic acid will remain in solution. Most parenteral nutrition solutions are buffered by the amino acids to pH 5 to 6.895
The rate of folic acid photodegradation is higher in an acidic medium compared to the rate in an alkaline medium.2496
Sorption
A parenteral nutrition solution containing 13 mcg/L of folic acid injection in a 3-L polyvinyl chloride (PVC) bag and run through an administration set delivered the full amount of folic acid, with no loss.895
Filtration
Folic acid (Lederle) 0.5 mg/L in dextrose 5% and sodium chloride 0.9% was filtered at 120 mL/hr for 6 hours through a 0.22-µm cellulose ester membrane filter (Ivex-2). No significant reduction due to binding to the filter was noted.533
Drugs in Syringe Compatibility
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Parenteral Nutrition Solutions
A 40% drop in folic acid concentration occurred immediately after admixture in a parenteral nutrition solution composed of amino acids, dextrose, electrolytes, trace elements, and multivitamins in PVC bags. The folic acid concentration then remained relatively constant for 28 days when stored at both 4 and 25°C.1063
Extensive decomposition of ascorbic acid and folic acid was reported in a parenteral nutrition solution composed of amino acids 3.3%, dextrose 12.5%, electrolytes, trace elements, and M.V.I.-12 (USV) in PVC bags. Half-lives were 1.1, 2.9, and 8.9 hours for ascorbic acid and 2.7, 5.4, and 24 hours for folic acid stored at 24°C in daylight, 24°C protected from light, and 4°C protected from light, respectively. The decomposition was much greater than for solutions not containing catalyzing metal ions. Also, it was greater than for the vitamins singly because of interactions with the other vitamins present.1059
Because of these interactions, recommendations to separate the administration of vitamins and trace elements have been made.1056; 1060; 1061 Other researchers have termed such recommendations premature based on differing reports895; 896 and the apparent absence of epidemic vitamin deficiency in parenteral nutrition patients.1062
The stability of several vitamins from M.V.I.-12 (Armour) admixed in parenteral nutrition solutions composed of different amino acid products, with or without Intralipid 10%, in glass bottles and PVC bags at 25 and 5°C for 48 hours was reported. Folic acid was stable in all samples.1431
In another study, the stability of several vitamins (from M.V.I.-12) following admixture with 4 different amino acid products (FreAmine III, Neopham, Novamine, Travasol) with or without Intralipid when stored in glass bottles or PVC bags at 25°C for 48 hours was reported. High-intensity phototherapy light did not affect folic acid. When bisulfite was added to the Neopham admixture, folic acid was unaffected. The authors concluded that intravenous multivitamins should be added to parenteral nutrition admixtures immediately prior to administration to reduce losses of vitamins other than folic acid since commercially available amino acid products may contain bisulfites and have varying pH values.487
The vitamins in Cernevit (Baxter) diluted in three 2-in-1 parenteral nutrition admixtures were tested for stability over 48 hours. Most of the other vitamins, including folic acid, retained their initial concentrations.2796
For a list of references cited in the text of this monograph, search the monograph titled References.