AHFS Class:

88:28 Multivitamin Preparations

Multivitamin products for parenteral administration are available in a variety of compositions and sizes. The following products are representative formulations.

Infuvite Adult and Infuvite Pediatric are available as single-dose or pharmacy bulk packages of 2 vials (labeled Vial 1 and Vial 2).⁴⁰³⁶; ⁴⁰³⁷

Infuvite Adult is available as a package of 2 vials (labeled Vial 1 and Vial 2) as a single-dose package or a pharmacy bulk package.⁴⁰³⁶ The quantities of each active ingredient are shown in Tables 1 and 2.⁴⁰³⁶

Table 1. Contents of Infuvite Adult Vial 1

Infuvite Adult Vial 1 also contains polysorbate 80 1.4% in water for injection with sodium hydroxide and/or hydrochloric acid for pH adjustment.⁴⁰³⁶

Table 2. Contents of Infuvite Adult Vial 2

Infuvite Adult Vial 2 also contains propylene glycol 30% in water for injection with citric acid and/or sodium citrate for pH adjustment.⁴⁰³⁶

Infuvite Adult single-dose package contains two 5-mL single-dose vials (labeled Vial 1 and Vial 2).⁴⁰³⁶ To prepare a dose using the single-dose package, add 5 mL from Vial 1 and 5 mL from Vial 2 to at least 500 to 1000 mL of a dextrose or saline infusion solution.⁴⁰³⁶

Infuvite Adult pharmacy bulk package contains a 50-mL vial (Vial 1) and a 100-mL vial containing 50 mL (Vial 2).⁴⁰³⁶ To prepare the pharmacy bulk package for dispensing, transfer the contents of Vial 1 (50 mL) into Vial 2 for a total volume of 100 mL; this provides ten 10-mL doses.⁴⁰³⁶ Each 10-mL dose should be added at least 500 to 1000 mL of a dextrose or saline infusion solution for intravenous administration.⁴⁰³⁶

Infuvite Pediatric is available as a package of 2 vials (labeled Vial 1 and Vial 2) as a single-dose package or a pharmacy bulk package.⁴⁰³⁷ The quantities of each active ingredient are shown in Tables 3 and 4.⁴⁰³⁷

Table 3. Contents of Infuvite Pediatric Vial 1

Infuvite Pediatric Vial 1 also contains, in each 4 mL, polysorbate 80 50 mg in water for injection with sodium hydroxide and/or hydrochloric acid for pH adjustment.⁴⁰³⁷

Table 2. Contents of Infuvite Pediatric Vial 2

Infuvite Pediatric Vial 2 also contains, in each mL, mannitol 75 mg in water for injection with citric acid and/or sodium citrate for pH adjustment.⁴⁰³⁷

Infuvite Pediatric single-dose package contains a 4-mL vial (Vial 1) and a 1-mL vial (Vial 2).⁴⁰³⁷ To prepare a dose using the single-dose package, add the appropriate weight-based doses from Vial 1 and Vial 2 to at least 100 mL of a dextrose or saline infusion solution.⁴⁰³⁷

Infuvite Pediatric pharmacy bulk package contains a 50-mL vial containing 40 mL (Vial 1) and a 10-mL vial (Vial 2).⁴⁰³⁷ To prepare the pharmacy bulk package for dispensing, transfer the contents of Vial 2 (10 mL) into Vial 2 (40 mL of solution) for a total volume of 50 mL; this provides ten 5-mL doses, fifteen 3.25-mL dose, or thirty-three 1.5-mL doses.⁴⁰³⁷ The appropriate dose should be added at least 100 mL of a dextrose or saline infusion solution for intravenous administration.⁴⁰³⁷

Aluminum Content

Infuvite Adult is stated to contain no more than 70 mcg of aluminum per L in Vials 1 and 2 combined.

Infuvite Pediatric is stated to contain no more than 30 mcg of aluminum per L in Vials 1 and 2 combined.⁴⁰³⁷

Trade Name(s)

Infuvite Adult, Infuvite Pediatric

Multivitamin infusion preparations are administered by intravenous infusion only after dilution.⁴⁰³⁶; ⁴⁰³⁷ Multivitamin preparations should not be administered undiluted or as a direct intravenous injection.⁴⁰³⁶; ⁴⁰³⁷

Intact containers should be stored at 2 to 8°C.⁴⁰³⁶; ⁴⁰³⁷ Exposure to light should be minimized because vitamins A, D, and riboflavin are light sensitive.⁴⁰³⁶; ⁴⁰³⁷

Dispensing from pharmacy bulk packages should be completed within 4 hours after initial entry into the vials.⁴⁰³⁶; ⁴⁰³⁷

Diluted solutions for infusion should be refrigerated and used within 24 hours.⁴⁰³⁶; ⁴⁰³⁷ Exposure to light should be minimized.⁴⁰³⁶; ⁴⁰³⁷

pH Effects

Infuvite is physically incompatible with alkaline solutions or drugs such as sodium bicarbonate, acetazolamide sodium, aminophylline, ampicillin sodium, or chlorothiazide sodium.⁴⁰³⁶; ⁴⁰³⁷

Light Effects

The effects of photoirradiation on a FreAmine II-dextrose 10% parenteral nutrition solution containing 1 mL/500 mL of multivitamins (USV) were evaluated. During simulated continuous administration to an infant at 0.156 mL/min, the amino acids were stable when the bottle, infusion tubing, and collection bottle were shielded with foil. Only 20 cm of tubing in the incubator was exposed to light. However, if the flow was stopped, marked reductions in methionine (40%), tryptophan (44%), and histidine (22%) occurred in the solution exposed to light for 24 hours. In a similar solution without vitamins, only the tryptophan concentration decreased. The difference was attributed to the presence of riboflavin, a photosensitizer. The authors recommended administering the multivitamins separately and shielding from light.⁸³³

The stability of 5 B vitamins was studied over 8 hours in representative parenteral nutrition solutions exposed to fluorescent light, indirect sunlight, or direct sunlight. One 5-mL vial of multivitamin concentrate (Lyphomed) and 1 mg of folic acid (Lederle) were added to a liter of parenteral nutrition solution composed of amino acids 4.25% and dextrose 25% (Travenol) with standard electrolytes and trace elements. The 5 B vitamins were stable for 8 hours at room temperature when exposed to fluorescent light. In addition, folic acid and niacinamide were stable over 8 hours in direct or indirect sunlight. Exposure to indirect sunlight appeared to have little or no effect on thiamine hydrochloride and pyridoxine hydrochloride in 8 hours, but riboflavin-5'-phosphate lost 47%. Direct sunlight caused a 26% loss of thiamine hydrochloride and an 86% loss of pyridoxine hydrochloride in 8 hours. A 4-hour exposure of riboflavin-5'-phosphate to direct sunlight resulted in a 98% loss.⁸⁴²

A parenteral nutrition solution in glass bottles exposed to sunlight was studied. Vitamin A decomposed rapidly, losing more than 50% in 3 hours. The decomposition could be slowed by covering the bottle with a light-resistant vinyl bag, resulting in about a 25% loss in 3 hours. Vitamin E was stable in the parenteral nutrition solution in glass bottles exposed to sunlight, with no loss occurring during 6 hours of exposure.¹⁰⁴⁰

Vitamin A rapidly and significantly decomposes when exposed to daylight. The extent and rate of loss were dependent on the degree of exposure to daylight which, in turn, depended on various factors such as the direction of the radiation, time of day, and climatic conditions. Delivery of less than 10% of the expected amount was reported.¹⁰⁴⁷ In controlled light experiments, the decomposition initially progressed exponentially. Subsequently, the rate of decomposition slowed. This result was attributed to a protective effect of the degradation products on the remaining vitamin A. The presence of amino acids provided greater protection. Compared to degradation rates in dextrose 5%, decomposition was reduced by up to 50% in some amino acid mixtures.¹⁰⁴⁸

The stability of several water-soluble vitamins in dextrose 5% and sodium chloride 0.9% in polyvinyl chloride (PVC) and ClearFlex containers was evaluated. Thiamine, riboflavin, ascorbic acid, and folic acid were stable at 23°C when protected from light, exhibiting 10% or less loss in 24 hours. When exposed to light, thiamine and folic acid were stable but ascorbic acid was reduced by approximately 50 to 65% and riboflavin was completely lost.¹⁵⁰⁹

The stability of phytonadione in a TPN solution containing amino acids 2%, dextrose 12.5%, “standard” electrolytes, and M.V.I. Pediatric over 24 hours while exposed to light was evaluated. Vitamin loss was about 7% in 4 hours and 27% in 24 hours. Some loss was attributed to the light sensitivity of the phytonadione.¹⁸¹⁵

Substantial loss of retinol all-trans palmitate and phytonadione was reported from both TPN and TNA admixtures due to exposure to sunlight. In 3 hours of exposure to sunlight, essentially total loss of retinol and 50% loss of phytonadione had occurred. The presence or absence of lipids did not affect stability. In contrast, tocopherol concentrations remained essentially unchanged by exposure to sunlight through 12 hours. The container material used to store the nutrition admixtures affected the concentration of the vitamins as well. Losses were greatest (10 to 25%) in PVC containers and were slightly better in EVA and glass containers.²⁰⁴⁹

Sorption

The following vitamins did not reveal significant sorption to a PVC plastic test strip in 24 hours:¹²

• Ascorbic acid
• Niacinamide
• Pyridoxine hydrochloride
• Riboflavin
• Thiamine hydrochloride
• Vitamin D
• Vitamin E acetate

Riboflavin was shown not to exhibit sorption to PVC bags and tubing, polyethylene tubing, Silastic tubing, and polypropylene syringes.⁵³⁶; ⁶⁰⁶

Vitamin A (as the acetate) (Sigma) 7.5 mg/L displayed 66.7% sorption to a PVC plastic test strip in 24 hours. The presence of dextrose 5% and sodium chloride 0.9% increased the extent of the sorption.¹²

In another report, vitamin A acetate 3 mg/L displayed 78% sorption to 200-mL PVC containers after 24 hours at 25°C with gentle shaking. The sorption was increased by 10% in sodium chloride 0.9% and by 20% in dextrose 5%.¹³³

However, vitamin A delivery is also reduced in glass intravenous containers. At a concentration of 10,000 units/L in glass and PVC plastic containers protected from light with aluminum foil, 77 and 71%, respectively, of the vitamin A were delivered over a 10-hour period. Without light protection, 61% was delivered from glass and 49% from PVC plastic containers over a 10-hour period.²⁹⁰

In another test using multivitamin infusion (USV), 1 ampul per liter of sodium chloride 0.9% in glass and PVC plastic containers not protected from light, 69.4 and 67.9% of the vitamin A were delivered from glass and PVC containers, respectively, over a 10-hour period. The amount of vitamin A was constant over the test period.²⁸²

The delivery of vitamins A, D, and E from a parenteral nutrition solution composed of 3% amino acid solution (Pharmacia) in dextrose 10% with electrolytes, trace elements, vitamin K, folate, and vitamin B₁₂ was evaluated. To this solution was added 6 mL of multivitamin infusion (USV). The solution was prepared in PVC bags (Travenol), and administration was simulated through a fluid chamber (Buretrol) and infusion tubing with a 0.5-µm filter at 10 mL/hr. During the first 60 to 90 minutes, minimal delivery of the vitamins occurred. This was followed by a rise and plateau in the delivered vitamins, which were attributed to an increasing saturation of adsorptive binding sites in the tubing. The total amounts delivered over 24 hours were 31% for vitamin A, 68% for vitamin D, and 64% for vitamin E. Sorption of the vitamins was found in the PVC bag, fluid chamber, and tubing. Decomposition was not a factor.⁸³⁶

A patient receiving 3000 international units of retinol daily in a parenteral nutrition solution experienced 2 episodes of night blindness. The pharmacy prepared the parenteral nutrition solution in 1-L PVC bags in weekly batches and stored them at 4°C in the dark until use. A subsequent in vitro study showed losses of vitamin A of 23 and 77% in 3- and 14-day periods, respectively, under these conditions. About 30% of the lost vitamin A could be extracted from the PVC bag.¹⁰³⁸

Vitamin A was lost from multivitamin infusion (USV) in a neonatal parenteral nutrition solution. The solution was prepared in colorless glass bottles and run through an administration set with a burette (Travenol). The total loss of vitamin A was 75% in 24 hours, with about 16% as decomposition in the glass bottle. The decomposition was not noticeable during the first 12 hours, but then vitamin A levels fell rather precipitously to about one-third of the initial amount. The balance of the loss, averaging about 59%, occurred during transit through the administration set. Removal of the inline filter and treatment of the set with albumin human had no effect on vitamin A delivery. Increasing three- to fourfold the amount of vitamin A was suggested to compensate for the losses.¹⁰³⁹

A 50% loss of vitamin A from a bottle of parenteral nutrition solution prepared with multivitamin infusion (USV) after 5.5 hours of infusion was noted. The amount delivered through an Ivex-2 filter set was only 6.3% of the added amount. Similar quantities were found after 20 hours of infusion. Vitamin A binding to the infusion bottles and tubing was confirmed.⁷⁰⁴

Solutions containing multivitamin infusion (USV) spiked with ³H-labeled retinol in intravenous tubing protected from light and agitated to simulate flow for 5 hours were evaluated. About half of the vitamin A was lost in 30 minutes, and 88 to 96% was lost in 5 hours.¹⁰⁴⁹

The stability of vitamin E (alpha-tocopherol acetate from M.V.I.-1000 or Soluzyme) and selenium (from Selepen) in amino acids (Abbott) and dextrose in PVC bags was studied. Exposure to fluorescent light and room temperature (23°C) for 24 hours and simulated infusion at 50 mL/hr for 8 hours through a Medlon TPN administration set with a 0.22-µm filter did not affect the concentrations of vitamin E and selenium.¹²²⁴

The stability of numerous vitamins in parenteral nutrition solutions composed of amino acids (Kabi-Vitrum), dextrose 30%, and lipid emulsion 20% (Kabi-Vitrum) in a 2:1:1 ratio with electrolytes, trace elements, and both fat- and water-soluble vitamins was reported. The admixtures were stored in darkness at 2 to 8°C for 96 hours with no significant loss of retinyl palmitate, alpha-tocopherol, thiamine mononitrate, sodium riboflavin-5'-phosphate, pyridoxine hydrochloride, nicotinamide, folic acid, biotin, sodium pantothenate, and cyanocobalamin. Sodium ascorbate and its biologically active degradation product, dehydroascorbic acid, totaled 59 and 42% of the nominal starting concentration at 24 and 96 hours, respectively.¹²²⁵

When the admixture was subjected to simulated infusion over 24 hours at 20°C, either exposed to room light or light protected, or stored for 6 days in the dark under refrigeration and then subjected to the same simulated infusion, once again the retinyl palmitate, alpha-tocopherol, and sodium riboflavin-5'-phosphate did not undergo significant loss. However, sodium ascorbate and its degradation product, dehydroascorbic acid, had initial combined concentrations of 51 to 65% of the nominal initial concentration, with further declines during infusion. Light protection did not significantly alter the loss of total ascorbic acid.¹²²⁵

Neonatal parenteral nutrition solutions containing multivitamin infusion prepared in bags were delivered at 10 mL/hr through Buretrol sets (Travenol). The bags and sets were protected from light. About 26% of the vitamin A was lost before the flow was started. At 10 mL/hr, about 67% was lost from the effluent. More rapid flow reduced the extent of loss. Analysis of clinical samples of parenteral nutrition solutions showed losses of 21 to 57% after 20 hours. Because losses after 5 hours were of the same magnitude, it was concluded that the loss occurs rapidly and is not due to decomposition.¹⁰⁴⁹

Retinol losses of 40% occurred in 2 hours and 60% in 5 hours from parenteral nutrition solutions pumped at 10 mL/hr through standard infusion sets at room temperature. The retinol concentration in the bottle remained constant while the retinol in the effluent decreased. Antioxidants had no effect. Much of the vitamin A was recoverable from the tubing.¹⁰⁵⁰

To minimize the importance of this sorption, Allwood suggested using vitamin A palmitate instead of acetate; he stated that vitamin A palmitate does not sorb to PVC. However, this does not alter the problem of degradation from exposure to light.¹⁰³³

Plasticizer Leaching

Multivitamins (Lyphomed) 1 mL in 50 mL of dextrose 5% leached insignificant amounts of diethylhexyl phthalate (DEHP) plasticizer due to the surfactant polysorbate 80 in the formulation. This finding is consistent with the low surfactant concentration (0.032%) in the admixture solution.¹⁶⁸³

Solution Compatibility

Additive Compatibility

Y-Site Injection Compatibility (1:1 Mixture)

Additional Compatibility Information

Parenteral Nutrition Solutions

In a parenteral nutrition solution composed of amino acids, dextrose, electrolytes, trace elements, and multivitamins in PVC bags stored at 4 and 25°C, vitamin A rapidly deteriorated to 10% of the initial concentration in 8 hours at 25°C when exposed to light. The decomposition was slowed by light protection and refrigeration, with a loss of about 25% in 4 days. Folic acid concentration dropped 40% initially on admixture and then remained relatively constant for 28 days of storage. About 35% of the ascorbic acid was lost in 39 hours at 25°C when exposed to light. The loss was reduced to a negligible amount in 4 days by refrigeration and light protection. Thiamine content dropped by 50% initially but then remained unchanged over 120 hours of storage.¹⁰⁶³

The stability of ascorbic acid in parenteral nutrition solutions, with and without lipid emulsion, was studied. Both with and without lipid emulsion, the total vitamin C content (ascorbic acid plus dehydroascorbic acid) remained above 90% for 12 hours when the solutions were exposed to fluorescent light and for 24 hours when they were protected from light. When stored in a cool dark place, the solutions were stable for 7 days.¹²²⁷

Samples from 24 1-L and four 2-L parenteral nutrition solutions, containing 1 vial each of multivitamin concentrate (USV), were evaluated for thiamine hydrochloride content 48 and 72 hours after mixing. The parenteral nutrition solutions contained amino acids 2.75 to 5%, dextrose 15 to 25%, and electrolytes. Thiamine hydrochloride was stable in all of the solutions tested in spite of approximately 0.05% sulfite content.⁸⁴³

The vitamins in Cernevit (Baxter) diluted in three 2-in-1 parenteral nutrition admixtures were tested for stability over 48 hours. Nearly all of the vitamins retained their initial concentrations. However, ascorbic acid exhibited losses of about 5%, 13%, and 17% in TPNs with dextrose concentrations of 10, 15, and 25%, respectively.²⁷⁹⁶

Erythromycin

Erythromycin 5 mg/mL as the lactobionate in pH 8 buffer was combined with riboflavin in concentrations varying from 1 mg/mL to 20 mcg/mL. On exposure to light for 4 hours, almost total decomposition of the erythromycin occurred, with only 4 to 12% remaining. Protection from light resulted in 12 to 25% decomposition. When no riboflavin was present, 10% or less decomposition of the erythromycin occurred. It was concluded that a photodynamic decomposition reaction was taking place.⁵⁶⁴

Penicillin G

The times to 10% decomposition of combinations of penicillin G potassium buffered with multivitamin infusion concentrate in dextrose 5% and sodium chloride 0.9% have been calculated on the pH of the admixture:³⁰⁴

For a list of references cited in the text of this monograph, search the monograph titled References.

ASHP^® Injectable Drug Information^TM. Selected Revisions December 5, 2024. © Copyright, 2024. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.