Alpha-tocopherol acetate/Ascorbic acid/Biotin/Cholecalciferol/Cyanocobalamin/Dexpanthenol/Folic acid/Niacinamide/Pyridoxine hydrochloride/Riboflavin 5'-phosphate sodium/Thiamine hydrochloride/Vitamin A palmitate/Vitamin K

On October 15, 2001, Baxter Healthcare Corporation (Deerfield, IL) announced that it had received approval from the Food and Drug Administration (FDA) to market a new adult parenteral multivitamin product, INFUVITE Adult. This product, manufactured by the Canadian firm Sabex, Inc (Boucherville, Quebec, Canada), is the first to meet the FDA’s amended requirements for marketing of an “effective” adult parenteral multivitamin formulation. The new requirements for increased dosages of vitamins B1, B6, and C and folic acid, as well as addition of vitamin K, are based on the recommendations from a 1985 workshop sponsored jointly by the American Medical Association’s (AMA) Division of Personal and Public Health Policy and FDA’s Division of Metabolic and Endocrine Drug Products. Specific modifications of the previous formulation include increasing the provision of ascorbic acid (vitamin C) from 100 mg/d to 200 mg/d, pyridoxine (vitamin B6) from 4 mg/d to 6 mg/d, thiamine (vitamin B1) from 3 mg/d to 6 mg/d, folic acid from 400 g/d to 600 g/d, and addition of phylloquinone (vitamin K) at 150 g/d. The implications of these changes are important for all healthcare practitioners involved in the care of patients receiving parenteral nutrition (PN). The presence of phylloquinone can interfere with the hypothrombinemic effect of anticoagulant therapy such as warfarin; thus, patients receiving this medication may need to have their prothrombin time and international normalized ratio (INR) closely monitored. The impact on vitamin compatibility and stability should also be recognized when using this product. The package insert alludes to the presence of aluminum, although the specific amount is not disclosed. Previous work has demonstrated that certain patient populations may be extremely vulnerable to aluminum toxicity. Burn patients receiving large quantities of human serum albumin and calcium gluconate, both of which are contaminated with aluminum, may be at an even greater risk for aluminum toxicity if they require PN with daily multivitamins. Alterations in bone formation, mineralization, parathyroid hormone (PTH) secretion, and urinary calcium excretion have been attributed to aluminum toxicity in long-term PN patients or patients with renal impairment. Ascorbic acid is the least stable of all multivitamins, and degradation leading to loss of biological activity has been reported. The amount of ascorbic acid degraded has been shown to directly correlate with the amount of oxygen present in the compounded bag. Degradation by direct reaction with oxygen has been identified as the primary mechanism. Sources of oxygen include infusions containing dissolved air such as glucose, introduction of air during transfer of additives from bottle to PN bag, and residual air in the compounded bag after sealing. Although one would presume that this would support the need for a higher intake of ascorbic acid, limitations to the safe provision of vitamin C in PN formulations should be carefully reviewed. Because the ascorbic acid degradation pathway results in the production of oxalic acid, the potential for calcium oxalate precipitation in a PN bag exists. Since the advent of “hyperalimentation,” practitioners have learned that more is not necessarily better. Will providing higher intakes of vitamins translate into better outcomes for our patients? Only time will provide the answer.

Multivitamins containing Tween 80 can cause anaphylactoid reactions. The objective of this study was to develop a new lipid emulsion containing 13 fat- and water-soluble vitamins for injection (13V-LE) that were simultaneously dissolved in one bottle and to evaluate the stability of and anaphylactoid reactions to 13V-LE.

Particle size, ζ-potential, and polydispersity of 13V-LE were assayed with a Zetasizer Nano ZS. Entrapment efficiency of 13V-LE was determined with HPLC. Behavior, histamine, and blood pressure of beagle dogs were investigated by observation, fluorospectrophotometry, and sphygmomanometry.

The 13V-LE with the smallest particles and highest entrapment efficiency with stable ζ-potential was composed of soybean oil, glycerin (2.25%, w:v), egg lecithin (1.2%, w:v), and purified water. There was no obvious change in characteristics of the 13V-LE samples in terms of appearance, size distribution, ζ-potential, pH value, or concentration over 6 months. In anaphylactoid reactions tests, when being administered with the multivitamin Infuvite Adult containing Tween 80, six beagles showed grade IV symptoms (P<0.01 vs control), low blood pressure, and high plasma-histamine concentrations (P<0.05 or P<0.01). However, there were no significant differences in behavior, blood pressure, or histamine concentration in the dogs before and after administration in the 13V-LE group.

The 13V-LE formulation is a suitable intravenous lipid emulsion without anaphylactoid reactions.