Propofol is available as a ready-to-use oil-in-water emulsion in 20-, 50-, and 100-mL vials.3499; 3500; 3501; 3502; 3503 Each mL contains propofol 10 mg along with soybean oil 100 mg, glycerol 22.5 mg, egg lecithin or phospholipids 12 mg, and sodium hydroxide to adjust the pH.3499; 3500; 3501; 3502; 3503 Propofol products are not identical.3499; 3500; 3501; 3502; 3503 Diprivan products contain disodium edetate 0.05 mg/mL (0.005%) as an antimicrobial agent.3499 Generic propofol formulations may contain benzyl alcohol 1.5 mg/mL,3500 benzyl alcohol 1.5 mg/mL and sodium benzoate 0.7 mg/mL,3501 sodium metabisulfite 0.25 mg/mL,3502 or sodium benzoate 1 mg/mL3503 as an antimicrobial agent. Additionally, Diprivan and some generic propofol formulations have differing pH values (see Products: pH), which also may contribute to differing compatibility results among the products.2336
Compatibility information for propofol with other drugs established using the Diprivan formulation should not be extrapolated to generic propofol products because of formulation differences.2336
pH
Diprivan has a pH ranging from 7 to 8.5.3499
The metabisulfite-containing formulation of propofol has a pH ranging from 4.5 to 6.6.3502 The benzyl alcohol-containing formulation has a pH ranging from 5.5 to 7.4.3500 The benzyl alcohol- and sodium benzoate-containing formulation and the sodium benzoate-containing formulations both have a pH ranging from 6 to 8.5.3501; 3503
Tonicity
Propofol 10 mg/mL injectable emulsion is isotonic.3499; 3500; 3501; 3502; 3503
Trade Name(s)
Diprivan
Before use, propofol should be shaken well.3499; 3500; 3501; 3502; 3503 Propofol is administered by intravenous injection or infusion; if necessary, propofol may be diluted with dextrose 5% to a concentration not less than 2 mg/mL.3499; 3500; 3501; 3502; 3503
Numerous outbreaks of serious postoperative infections have resulted from inadvertent contamination of propofol.1930; 3499; 3500; 3501; 3502; 3503 The contamination resulted from risky preparation practices and lapses in aseptic technique.1930 The lipid base supports microbiological growth.1930; 3499; 3500; 3501; 3502; 3503 The disodium edetate, sodium metabisulfite, or benzyl alcohol and/or sodium benzoate in the formulations can retard the growth of microorganisms for up to 12 hours, but the products can still support growth and are not antimicrobially preserved.3499; 3500; 3501; 3502; 3503 Strict aseptic procedures are required during handling.3499; 3500; 3501; 3502; 3503
Propofol injection is a white, oil-in-water emulsion.3499; 3500; 3501; 3502; 3503 Intact containers should be stored at 4 to 25°C3499; 3500; 3502; 3503 or 20 to 25°C.3501 Vials should not be frozen.3499; 3500; 3501; 3502; 3503 The emulsion should not be used if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if other forms of phase separation indicating compromised stability are present.3499; 3500; 3501; 3502; 3503
Because propofol undergoes oxidative degradation when exposed to oxygen, intact containers are packaged under nitrogen to avoid oxygen exposure.3499; 3500; 3501; 3502; 3503 Whether propofol is administered directly from the vial or drawn into a syringe, administration should begin immediately and should be completed within 12 hours after the vial is spiked.3499; 3500; 3501; 3502; 3503 The tubing and any unused propofol should be discarded after 12 hours.3499; 3500; 3501; 3502; 3503
Propofol formulated with sodium metabisulfite antioxidant is subject to a differing decomposition reaction compared with the edetate-containing Diprivan formulation. Exposure to air results in the formation of a yellow discoloration in about 6 to 7 hours, which does not occur with Diprivan. The yellow discoloration is a result of the formation of oxidized propofol dimer quinone from sulfite radicals that form in the generic product and may be associated with increased adverse effects. This oxidation product does not form in Diprivan containing edetate.2344; 2575; 2576 Stability information for propofol established using the Diprivan formulation should not be extrapolated to generic formulations.2336; 2344
The physical stability of both Diprivan and propofol containing sodium metabisulfite was evaluated. The formulation differences, principally pH, resulted in a much higher zeta potential for Diprivan, making it a more rugged emulsion and less subject to damage from physical agitation and thermal insult. Physical agitation resulted in no increase in fat droplet size in Diprivan after 16 hours, but a substantial increase in fat droplets larger than 5 µm occurred in as little as 4 hours in the sodium metabisulfite-containing formulation.2445
One benzyl alcohol-containing formulation of propofol had the same pH as Diprivan (pH 7 to 8.5) and exhibited the same degree of ruggedness and resistance to emulsion disruption as Diprivan.2659
In another study, propofol (Diprivan) was again reported to be a more rugged emulsion than the generic formulation containing sodium metabisulfite. Diprivan had a very low quantity of fat globules exceeding 5 µm throughout its shelf life. The sodium metabisulfite-containing formulation formed much greater amounts of globules of 5 µm or larger within a few months after manufacture and well before the expiration date. This 5-µm or larger globule size is an important threshold because globules of this size may occlude capillaries and lead to embolic syndrome. The safety of using this sodium metabisulfite-containing formulation of propofol, especially as the product nears its expiration date, was questioned.2589
Propofol emulsion is a single-access product and can support the growth of microorganisms.1930; 3499; 3500; 3501; 3502; 3503 In one study, propofol strongly supported the growth of Escherichia coli and Candida albicans.2411 Strict adherence to proper aseptic procedures, including disinfecting the vial stopper with isopropyl alcohol 70%, is required.3499; 3500; 3501; 3502; 3503 Use of the drug within 6 hours has been recommended.2411
Plastic and Glass Containers
Diluted in dextrose 5%, propofol has been shown to be more stable in glass than in plastic containers; manufacturers indicate that only 95% of the drug remains after only 2 hours of a running infusion in plastic (material unspecified).3499; 3500; 3501; 3502; 3503
Syringes
Propofol (Diprivan) 10 mg/mL was repackaged into 60-mL polypropylene syringes (Monoject, Sherwood Medical) and stored at 23°C under fluorescent light and at 4°C protected from light. No visually apparent changes occurred to the emulsion under either storage condition. Propofol losses were 7% in 5 days and 12% in 7 days in the room-temperature samples. No propofol losses occurred in 13 days in the refrigerated samples.1984
Propofol (Diprivan) 1% was repackaged into 2- and 10-mL Plastipak (Becton Dickinson) and 2-mL Injekt (B. Braun) plastic syringes and was stored at 5°C. Propofol losses were about 7 to 8% in the Plastipak syringes and about 2% in the Injekt syringes after 28 days of refrigerated storage.2118
Sorption
Propofol (Diprivan) injection was diluted to 2 mg/mL with dextrose 5% and stored in polyvinyl chloride (PVC) tubing (Kendall-McGaw). A propofol loss exceeding 31% occurred after static storage for 2 hours. In simulated infusions using the same initial concentration, administration through 72-inch PVC administration sets at a rate of 1.75 mL/min resulted in an average propofol loss of 7.7% over the 2-hour period.2057
When tested undiluted at 10 mg/mL, propofol (Diprivan) sorption to administration tubing composed principally of PVC did not represent a substantial portion of the total amount of drug delivered. Any losses that did occur were within the error of the method and were not clinically relevant.2297
Propofol (Diprivan) was delivered at rates of 1 and 10 mL/hr through PVC tubing. Little loss occurred at the higher rate of delivery. However, at the slower rate, up to 6% propofol loss due to sorption occurred.2468
Plasticizer Leaching
As happens with surfactant-containing drug formulations, propofol emulsion also has been shown to leach diethylhexyl phthalate (DEHP) plasticizer from PVC equipment such as administration sets. The use of non-PVC administration sets has been recommended.2424
Filtration
When filtration is clinically appropriate, manufacturers recommend that propofol be administered with caution only through a filter with a pore size of 5 µm or greater, unless the filter has demonstrated no effects on flow and/or breakdown of the emulsion.3499; 3500; 3501; 3502; 3503 Continuous monitoring for restricted flow and/or emulsion breakdown is necessary if a filter is used.3499; 3500; 3501; 3502; 3503 Filters with a pore size less than 5 µm should not be used.3499; 3500; 3501; 3502; 3503
Propofol (Diprivan) 1% 10 mL filtered through a 5-µm filter needle (Burron Medical) underwent no loss.2057
Standardize 4 Safety
One or more standardized concentrations for this drug have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. (See Standardize 4 Safety in Users Guide.) Recommendations developed to date through this initiative are available at www.ashp.org/pharmacy-practice/standardize-4-safety-initiative.
Table 1: Standardize 4 Safety Continuous IV Infusion Standard Concentrations for Propofol3635; 3636
| Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
| Adults | 10 mg/mL | mcg/kg/minute (note dosing units differ from concentration units) |
| Pediatric patients (50 kg) | 10 mg/mL | mcg/kg/minute (note dosing units differ from concentration units) |
For a list of references cited in the text of this monograph, search the monograph titled References.