Handbook on Injectable Drugs - 15th Ed.

(2009)
Thursday, January 21, 2016
11:01 AM

Paclitaxel - AHFS 10:00

Products  Paclitaxel is available as 6-mg/mL non-aqueous concentrated solutions that must be diluted for use. Taxol is available in 5 -, 16.7-, and
50-mL multiple-dose vials while Onxol is available in 5-, 25-, and 50-mL multiple-dose vials. One milliliter of either formulation provides paclitaxel 6
mg with polyoxyl 35 castor oil (Cremophor EL; polyoxyethylated castor oil) surfactant 527 mg and dehydrated alcohol 49.7% (v/ v). The Onxol
formulation also incorporates citric acid anhydrous 2 mg/mL. (1-2/06) (4)

pH  Paclitaxel admixtures at concentrations of 0.6 and 1.2 mg/mL in dextrose 5%, sodium chloride 0.9%, and dextrose 5% in lactate d Ringer's
injection have a pH of 4.4 to 5.6. (4)

Trade Name(s)  Onxol, Taxol

Administration  Paclitaxel is administered by intravenous infusion. The concentrate must be diluted to a final paclitaxel concentration of 0. 3 to 1.2
mg/mL in dextrose 5%, sodium chloride 0.9%, dextrose 5% in sodium chloride 0.9%, or dextrose 5% in lactated Ringer's injectio n. Administration
over three hours is often recommended (1-2/06) (4), although other duration periods have been used. (4) An inline 0.22-m filter should be used for
administration. The intravenous solution containers and administration sets should be free of the plasticizer diethylhexyl ph thalate (DEHP). (1-2/06)
See Plasticizer Leaching under Stability below.

Use of self-venting sets spiked into glass bottles of paclitaxel admixtures has occasionally resulted in solution dripping from the air v ent. Presumably,
the surfactant content wetted the hydrophobic filter, allowing the solution to drip. ( 1843) In another observation, the spikes of administration sets
were made sufficiently slippery by surfactant in the paclitaxel formulation that the spike slipped out after it had been seat ed through the rubber
bung of the glass bottle. The admixture also leaked due to a poor seal. The authors recommend use of non -PVC plastic solution containers (Excel,
McGaw) to avoid the problem. (2052)

Stability  Intact vials should be stored between 20 and 25 C and protected from light. Stability is not adversely affected by refrigeration or
freezing. Refrigeration may result in the precipitation of formulation components. However, warming to room temperature redis solves the material
and does not adversely affect the product. If a precipitate is insoluble, the product should be discarded. ( 1-2/06)

Turbidity  Paclitaxel concentrate is a clear, colorless to slightly yellow viscous liquid. After dilution in an infusion solution, the d rug may exhibit
haziness because of the surfactant content of the formulation. (1528) This haziness increases until the maximum turbidity of around 6 to 8
nephelometric turbidity units occurs between 0.3 and 0.9 mg/mL. This level of haze may be visible in normal room light. Conti nued dilution below
0.3 mg/mL results in a continual decline of measured turbidity through 0.01 mg/mL, the lowest concentration evaluated. ( 1528)

Precipitation  Although paclitaxel in aqueous solutions is chemically stable for 27 hours ( 1-2/06) or longer (1746) (1842) (2708), precipitation has
occurred irregularly and unpredictably. Such precipitation occurs within the recommended range of 0.3 to 1.2 mg/mL and at eve n lower paclitaxel
concentrations. These precipitates often have been observed in the infusion tubing distal to the pump chamber. ( 1716) Although the precipitation of
insoluble drugs in an aqueous medium is a foregone conclusion, the time to precipitation is irregular. It may be accelerated by various factors
including the presence or formation of crystallization nuclei, agitation, and contact with incompatible drugs or materials. ( 1374) (1521) Since the
mechanism of this irregular paclitaxel precipitation has not been identified ( 1739), care and vigilance throughout its infusion are required.

Sorption  No paclitaxel loss due to sorption to containers or sets has been observed. ( 1520) (2230) (2231) (2232)

Plasticizer Leaching  Contact of undiluted paclitaxel concentrate with plasticized PVC equipment and devices is not recommended. ( 1-2/06) (4)
With use of infusion bags and tubing that are free of DEHP plasticizer and the elimination of PVC precision flow regulators, a reduction in leached
DEHP of up to 96% has been reported. (2679)

Paclitaxel vehicle equivalent to paclitaxel 1.2 mg/mL in dextrose 5% in VISIV polyolefin bags was tested at room temperature near 23 C for 24 hours.
HPLC analysis found no leached plastic components within the 24-hour study period. (2660)

Paclitaxel itself does not contribute to the extraction of the plasticizer DEHP. ( 1520) However, the surfactant, Cremophor EL, in the paclitaxel
formulation extracts DEHP from PVC containers and sets. The amount of DEHP extracted increases with time and drug concentrati on. (1520) (1683)
(2146) Consequently, the use of DEHP-plasticized PVC containers and sets is not recommended for infusion of paclitaxel solutions. Instead, the
manufacturer recommends the use of glass, polypropylene, or polyolefin containers and non -PVC administration sets such as those that are
polyethylene lined. (1-2/06)

The use of inline filters, such as the Ivex-2 filter set that incorporates about 10 inches of PVC inlet and outlet tubing, has resulted in a small amount
of DEHP extraction. Since the extracted DEHP is at a sufficiently low level, however, the manufacturer considers the Ivex -2 filter set to be acceptable.
(1-2/06)

A study was performed on the compatibility of paclitaxel 0.3- and 1.2-mg/mL infusions with various non-PVC infusion sets. The paclitaxel infusions

Unfiled Notes Page 1

A study was performed on the compatibility of paclitaxel 0.3- and 1.2-mg/mL infusions with various non-PVC infusion sets. The paclitaxel infusions
were run through the study sets, and the effluent was then analyzed by HPLC for leached DEHP plasticizer. The following sets had significant and
unacceptable amounts of leached DEHP: Baxter vented nitroglycerin (2C7552S), Baxter vented basic solution (1C8355S), McGaw Ho rizon pump
vented nitroglycerin (V7450), and McGaw Intelligent pump vented nitroglycerin (V7150). Although these sets were largely non -PVC, their highly
plasticized pumping segments contributed the DEHP. The administration and extension sets cited in Tables 1 and 2 exhibited no more leached DEHP
than the Ivex-2 filter set specified in the product labeling. (1843)

Table 1. Administration Sets Compatible with Paclitaxel Infusions by Manufacturer 1843

Abbott LifeCare 5000 Plum PVC specialty set (11594)
Life Shield anesthesia pump set OL with cartridge (13503)
LifeCare model 4P specialty set, non-PVC (11434)
Omni-Flow universal primary intravenous pump short minibore patient line (40527)
Baxter Vented volumetric pump nitroglycerin set (2C1042)
Block Medical Verifuse nonvented administration set with 0.22-m filter, check valve, injection site, and non-DEHP PVC tubing (V021015)
I-Flow Vivus-4000 polyethylene-lined infusion set (5000-784)
IMED Standard PVC set (9215)
Closed-system non-PVC fluid path nonvented quick-spike administration set (9635)
Non-PVC set with inline filter (9986)
Gemini 20 nonvented primary administration set for nitroglycerin and emulsions (2262)
IVAC Universal set with low-sorbing tubing (52053, 59953, and S75053)
Ivion/Medex WalkMed spike set (SP-06) with pump set (PS-401, PS-360, FPS-560, or FPX-560)
Siemens Reduced-PVC full set MiniMed Uni-Set macrobore (28-60-190)
Table 2. Extension Sets Compatible with Paclitaxel Infusions by Manufacturer 1843
Abbott Ivex-HP filter set (4524)
Ivex-2 filter set (2679)
Becton-Dickinson Intima intravenous catheter placement set (38-6918-1)
J-loop connector (38-1252-2)
E-Z infusion set shorty (38-53741)
E-Z infusion set (38-53121)
Baxter Polyethylene-lined extension set with 0.22-m air-eliminating filter (1C8363)
Braun 0.2-m filter extension set (FE-2012L)
Small-bore 0.2-m filter extension set (PFE-2007)
Whin-winged extension set with 90 Huber needle (HW-2267)
Whin extension set with Y-site and Huber needle (HW-2276 YHR)
Y-extension set with valve (ET-08-YL)
Small-bore extension set with T-fitting (ET-04T)
Small-bore extension set with reflux valve (ET-116L)
Gish Biomedical VasTack noncoring portal-access needle system (VT-2022)
IMED 0.2-m add-on filter set (9400 XL)
IVAC Spec-Sets extension set with 0.22-m inline filter (C20028 and C20350)
Ivion/Medex Extension set with 0.22-m filter (IV4A07-IV3)
PALL SetSaver extended-life disposable set with 0.2-m filter (ELD-96P and ELD-96LL)
SetSaver extended-life disposable microbore extension tubing with 0.2-m Posidyne filter (ELD-96LYL and ELD-96LYLN)
Pfizer/Strato Medical Lifeport vascular-access system infusion set with Y-site (LPS 3009)
Mazzo et al. evaluated the leaching of DEHP plasticizer by paclitaxel 0.3 and 1.2 mg/mL in dextrose 5% and in sodium chloride 0.9%. PVC bags of the
solutions were used to prepare the admixtures. The leaching of the plasticizer was found to be time and concentration depende nt; however, there
was little difference between the two infusion solutions. After storage for eight hours at 21 C, HPLC analysis found leached DEHP in the range from
73 to 108 g/mL for the 1.2 mg/mL concentration and from 21 to 30 g/mL for the 0.3 mg/mL concentration. During a simulated one-hour infusion
using DEHP plasticized administration sets, the amount of leached DEHP did not exceed 18 g/mL at the 0.3 mg/mL paclitaxel concentration but
resulted in a maximum of 114 g/mL with the 1.2 mg/mL concentration. (1825)

Allwood and Martin confirmed the leaching of DEHP plasticizer from PVC containers and administration sets, and the amount of DEHP leached was

Unfiled Notes Page 2

Allwood and Martin confirmed the leaching of DEHP plasticizer from PVC containers and administration sets, and the amount of DEHP leached was
again found to depend on surfactant concentration and length of contact period. They also reported leaching of up to 30 mg of DEHP per dose from
Flo-Gard Low Adsorption Sets (Baxter), a set with a reduced amount of PVC present in its construction. ( 2146)

An acceptability limit of no more than 5 parts per million (5 g/mL) for DEHP plasticizer released from PVC containers, administration sets, and other
equipment has been proposed. The limit was proposed based on a review of metabolic and toxicologic considerations. ( 2185)

The acceptability of two reduced-phthalate administration sets for the Acclaim (Abbott) pump was evaluated. Administration set model 11993 -48
(Abbott) is composed of polyethylene tubing but has a DEHP-plasticized pumping segment. Administration set model L-12060 (Abbott) is composed
of tris(2-ethylhexyl)trimellitate (TOTM)-plasticized PVC tubing and a DEHP-plasticized pumping segment. Paclitaxel diluent at concentrations
equivalent to 0.3 and 1.2 mg/mL in dextrose 5% delivered rapidly over three hours at 23 C did not leach detectable levels of TOTM from model
L-12060 or DEHP from either set using HPLC analysis. Similarly, slow delivery over four days of the 0.3 -mg/mL concentration yielded detectable but
not quantifiable amounts of plasticizer. However, slow delivery of the equivalent of 1.2 mg/mL over four days yielded large b ut variable amounts of
DEHP from both sets; DEHP concentrations ranged from 30 to 150 g/mL. Consequently, these two reduced-phthalate sets are suitable for short-
term delivery up to three hours of paclitaxel at concentrations up to 1.2 mg/mL. However, these sets should not be used for s low delivery of higher
concentrations. (2198)

The admonition of the paclitaxel labeling to avoid PVC administration sets was found not to extend to a TOTM -plasticized PVC set (SoloPak).
Paclitaxel vehicle equivalent to paclitaxel 0.3 and 1.2 mg/mL in dextrose 5% did not leach TOTM plasticizer from the set duri ng simulated three-hour
administration. During extremely slow delivery at 5.2 mL/hr for four days, no detectable TOTM was found in the 0.3 -mg/mL equivalent
concentration, and only a barely detectable, unquantifiable, trace amount of TOTM was found with the 1.2 -mg/mL equivalent solution. (2232)

Paclitaxel (Faulding) 0.3 and 1.2 mg/mL in dextrose 5% or in sodium chloride 0.9% in ethylene vinyl acetate (EVA) plastic con tainers was found to
leach an unknown material after storage at 25 and 32 C for 24 hours. (2182)

Filtration  The manufacturer recommends the use of a 0.22-m inline filter for paclitaxel administration. (1-2/06) No loss of paclitaxel due to
filtration through 0.22-m filters has been observed. (1-2/06) (1520)

The acceptability of the 0.22-m IV Express Filter Unit (Millipore) for the administration of paclitaxel was evaluated. Paclitaxel vehicle equivalent to
paclitaxel 1.2 mg/mL (for plasticizer leaching) and paclitaxel 0.3 mg/mL (for sorption potential) in 500 mL of dextrose 5% in polyolefin containers
(McGaw) was delivered through the filter units over a three-hour period at a rate of 167 mL/hr at about 23 C to simulate paclitaxel administration.
HPLC analysis found no leached plasticizer and no loss of paclitaxel due to sorption. The filter unit was determined to be ac ceptable for the
administration of paclitaxel infusions. (2231)

Central Venous Catheter  The acceptability of the Arrow-Howes triple-lumen, 7 French, 30-cm polyurethane central catheter (Arrow International)
for the administration of paclitaxel was evaluated. Paclitaxel vehicle equivalent to paclitaxel 0.3 and 1.2 mg/mL (for cathet er component leaching)
and paclitaxel 0.3 mg/mL (for sorption potential) were prepared in polyolefin bags of dextrose 5% (McGaw). The solutions were delivered through
the polyurethane central venous catheters for periods of three hours and of 24 hours at 23 C to simulate rapid and slow administration. HPLC
analysis found no leached catheter components in the effluent solution and no loss of paclitaxel due to sorption. The Arrow -Howes polyurethane
central venous catheter was determined to be acceptable for the administration of paclitaxel infusions in the concentration r ange of 0.3 to 1.2
mg/mL over short or long delivery periods. (2230)

Compatibility Information

Solution Compatibility

Paclitaxel
Solution Mfr Mfr Conc/L Remarks Ref C/I
Dextrose 5% MG, TRa NCI 0.3, 0.6, 0.9 Visually compatible with no paclitaxel loss by HPLC over 12 hr at 22 C 1520 C
g
Dextrose 5% MGb NCI 0.6 g Visually compatible with no paclitaxel loss by HPLC over 25 hr at 22 C 1520 C
Dextrose 5% MG, TRc NCI 1.2 g Visually compatible with no paclitaxel loss by HPLC over 12 hr at 22 C 1520 C
Dextrose 5% BR 0.2 to 0.58 Fluffy, white precipitate forms occasionally in administration set just distal 1716 I
g to pump chamber
Dextrose 5% MGb BR 0.1 and 1 g Physically compatible with no change in subvisual haze or particle content 1746 C
and stable by HPLC for 3 days at 4, 22, and 32 C. Small, needlelike crystals
form after 3 days
Dextrose 5% MGb BR 0.3 and 1.2 Physically compatible and chemically stable for 48 hr at 22 C 1842 C
g
Dextrose 5% BAd FAU 0.3 and 1.2 Physically compatible with no change in subvisual haze or particle content 2182 ?
g and stable by HPLC for 3 days at 25 and 32 C. Unknown material leached
from EVA container by 24 hr

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 from EVA container by 24 hr
Dextrose 5% BAb, BRNb, BMS 0.3 and 1.2 Physically compatible with less than 5% paclitaxel loss in 72 hr at 37 C in 2669 C
FREb, MACb g the dark
Dextrose 5% BRNe BMS 0.4 and 1.2 Physically compatible with little paclitaxel loss in 5 days at 23 and 4 C. 2673 C
g Precipitation occurred after that time
Dextrose 5% BAf TE 0.3 mg/mL Chemically stable until precipitation. Precipitate found after 3 days at 25 C 2708 C
and 13 days at 5 C
Dextrose 5% BRNe TE 0.3 mg/mL Chemically stable until precipitation. Precipitate found after 3 days at 25 C 2708 C
and 18 days at 5 C
Dextrose 5% BRNg TE 0.3 mg/mL Chemically stable until precipitation. Precipitate found after 7 days at 25 C 2708 C
and 20 days at 5 C
Dextrose 5% BAf TE 1.2 mg/mL Chemically stable until precipitation. Precipitate found after 3 days at 25 C 2708 C
and 10 days at 5 C
Dextrose 5% BRNe TE 1.2 mg/mL Chemically stable until precipitation. Precipitate found after 3 days at 25 C 2708 C
and 12 days at 5 C
Dextrose 5% BRNg TE 1.2 mg/mL Chemically stable until precipitation. Precipitate found after 7 days at 25 C 2708 C
and 10 days at 5 C
Sodium MG, TRa NCI 0.3, 0.6, Visually compatible with no paclitaxel loss by HPLC over 12 hr at 22 C 1520 C
chloride 0.9% 0.9, 1.2 g
Sodium MGb NCI 0.6 and 1.2 Visually compatible with no paclitaxel loss by HPLC over 26 hr at 22 C 1520 C
chloride 0.9% g
Sodium MGb BR 0.1 and 1 g Physically compatible with no change in subvisual haze or particle content 1746 C
chloride 0.9% and stable by HPLC for 3 days at 4, 22, and 32 C. Small, needlelike crystals
form after 3 days
Sodium MGb BR 0.3 and 1.2 Physically compatible and chemically stable for 48 hr at 22 C 1842 C
chloride 0.9% g
Sodium BAd FAU 0.3 and 1.2 Physically compatible with no change in subvisual haze or particle content 2182 ?
chloride 0.9% g and stable by HPLC for 3 days at 25 and 32 C. Unknown material leached
from EVA container by 24 hr
Sodium BAb, BRNb, BMS 0.3 and 1.2 Physically compatible with less than 5% paclitaxel loss in 72 hr at 37 C in 2669 C
chloride 0.9% FREb, MACb g the dark
Sodium BAf TE 0.3 mg/mL Chemically stable until precipitation. Precipitate found after 3 days at 25 C 2708 C
chloride 0.9% and 13 days at 5 C
Sodium BRNe TE 0.3 mg/mL Chemically stable until precipitation. Precipitate found after 3 days at 25 C 2708 C
chloride 0.9% and 16 days at 5 C
Sodium BRNg TE 0.3 mg/mL Chemically stable until precipitation. Precipitate found after 3 days at 25 C 2708 C
chloride 0.9% and 13 days at 5 C
Sodium BAf TE 1.2 mg/mL Chemically stable until precipitation. Precipitate found after 3 days at 25 C 2708 C
chloride 0.9% and 9 days at 5 C
Sodium BRNe TE 1.2 mg/mL Chemically stable until precipitation. Precipitate found after 3 days at 25 C 2708 C
chloride 0.9% and 12 days at 5 C
Sodium BRNg TE 1.2 mg/mL Chemically stable until precipitation. Precipitate found after 5 days at 25 C 2708 C
chloride 0.9% and 8 days at 5 C

aTested in both glass and PVC containers.

bTested in polyolefin containers.

cTested in glass, PVC, and polyolefin containers.

dTested in Baxter ethylene vinyl acetate (EVA) containers.

eTested in ECOFLAC low-density polyethylene plastic containers.

fTested in polyolefin containers.

gTested in glass containers.

Unfiled Notes Page 4

gTested inglass containers.
Additive Compatibility

Paclitaxel
Drug Mfr Conc/L Mfr Conc/L Test Remarks Ref C/I
Soln
Carboplati BMS 2g BMS 300 mg NS No paclitaxel loss but carboplatin losses of 2, 5, and 7% at 4, 24, 2094 C
n and 1.2 g and 32 C, respectively, in 24 hr by HPLC. Physically compatible for
24 hr but subvisual particulates of paclitaxel form after 3 to 5 days
BMS 2g BMS 300 mg D5W No paclitaxel and carboplatin loss by HPLC at 4, 24, and 32 C in 24 2094 C
and 1.2 g hr. Physically compatible for 24 hr but subvisual particulates of
paclitaxel form after 3 to 5 days
Cisplatin BMS 200 mg BMS 300 mg NS No paclitaxel loss and cisplatin losses of 1, 4, and 5% at 4, 24 and 2094 C
32 C, respectively, in 24 hr by HPLC. Physically compatible for 24
hr but subvisual particulates of paclitaxel form after 3 to 5 days
BMS 200 mg BMS 1.2 g NS No paclitaxel loss but cisplatin losses of 10, 19, and 22% at 4, 24, 2094 I
and 32 C, respectively, in 24 hr by HPLC. Physically compatible for
24 hr but subvisual particulates of paclitaxel form after 3 to 5 days
Doxorubic PH 200 mg BMS 300 mg D5W, Visually compatible for at least 1 day with microprecipitation 2247 C
in HCl NS appearing in 3 to 5 days and gross precipitation in 7 days at 4, 23,
and 32 C protected from light. No paclitaxel loss and less than 8%
doxorubicin loss in 7 days
PH 200 mg BMS 1.2 g D5W, Visually compatible for at least 1 day with microprecipitation 2247 C
NS appearing in 3 to 5 days and gross precipitation in 7 days at 4, 23,
and 32 C protected from light. No paclitaxel loss and less than 7%
doxorubicin loss in 7 days
Y-Site Injection Compatibility (1:1 Mixture)

Paclitaxel
Drug Mfr Conc Mfr Conc Remarks Ref C/I
Acyclovir sodium BW 7 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Amikacin sulfate BR 5 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Aminophylline AB 2.5 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Amphotericin B SQ 0.6 mg/mLa NCI 1.2 mg/mLa Immediate increase in measured turbidity followed by 1556 I
separation into two layers in 24 hr at 22 C
Amphotericin B SEQ 0.83 mg/mLa MJ 0.6 mg/mLa Decreased natural turbidity occurs immediately 2117 I
cholesteryl sulfate
complex
Ampicillin sodium- RR 20 + 10 NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
sulbactam sodium mg/mLb turbidity in 4 hr at 22 C
Anidulafungin VIC 0.5 mg/mLa MJ 0.6 mg/mLa Physically compatible with no change in measured 2617 C
turbidity or increase in particle content in 4 hr at 23 C
Bleomycin sulfate MJ 1 unit/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Butorphanol tartrate BR 0.04 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Calcium chloride AST 20 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Carboplatin 5 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Cefepime HCl BMS 20 mg/mLa BR 0.6 mg/mLa Physically compatible with no change in measured 1689 C
turbidity or increase in particle content in 4 hr at 22 C
Cefotetan disodium STU 20 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C

Unfiled Notes Page 5

 turbidity in 4 hr at 22 C
Ceftazidime LIf 40 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Ceftriaxone sodium RC 20 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Chlorpromazine HCl ES 2 mg/mLa NCI 1.2 mg/mLa Normal inherent haze from paclitaxel decreases 1556 I
immediately
Cimetidine HCl 12 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Cisplatin 1 mg/mL NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Cladribine ORT 0.015b and BR 0.6 mg/mLb Physically compatible with no change in measured 1969 C
0.5c mg/mL turbidity or increase in particle content in 4 hr at 23 C
Cyclophosphamide 10 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Cytarabine 50 mg/mL NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Dacarbazine MI 4 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Dexamethasone 1 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
sodium phosphate turbidity in 4 hr at 22 C
Diphenhydramine HCl 2 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Doxorubicin HCl 2 mg/mL NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Doxorubicin HCl SEQ 0.4 mg/mLa MJ 0.6 mg/mLa Partial loss of measured natural turbidity 2087 I
liposome injection
Droperidol JN 0.4 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Etoposide 0.4 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Etoposide phosphate BR 5 mg/mLa MJ 1.2 mg/mLa Physically compatible with no change in measured 2218 C
turbidity or increase in particle content in 4 hr at 23 C
Famotidine MSD 2 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Floxuridine RC 3 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Fluconazole RR 2 mg/mL NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
PF 2 mg/mL BR 0.3 and 1.2 Visually compatible with no loss of either drug by HPLC 1790 C
mg/mLa in 4 hr at 23 C
Fluorouracil 16 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Furosemide AST 3 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Ganciclovir sodium SY 20 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Gemcitabine HCl LI 10 mg/mLb MJ 1.2 mg/mLa Physically compatible with no change in measured 2226 C
turbidity or increase in particle content in 4 hr at 23 C
Gentamicin sulfate ES 5 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Granisetron HCl SKB 1 mg/mL MJ 0.3 mg/mLb Physically compatible with little or no loss of either drug 1883 C
by HPLC in 4 hr at 22 C
SKB 0.05 mg/mLa MJ 1.2 mg/mLa Physically compatible with no change in measured 2000 C
turbidity or increase in particle content in 4 hr at 23 C

Unfiled Notes Page 6

 turbidity or increase in particle content in 4 hr at 23 C
Haloperidol lactate 0.2 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Heparin sodium WY 100 units/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Hydrocortisone AB 1 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
sodium succinate turbidity in 4 hr at 22 C
Hydromorphone HCl KN 0.5 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Hydroxyzine HCl ES 4 mg/mLa NCI 1.2 mg/mLa Normal inherent haze from paclitaxel decreases 1556 I
immediately
Ifosfamide BR 25 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Linezolid PHU 2 mg/mL MJ 0.6 mg/mLa Physically compatible with no change in measured 2264 C
turbidity or increase in particle content in 4 hr at 23 C
Lorazepam 0.1 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Magnesium sulfate AST 100 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Mannitol BA 15% NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Meperidine HCl WY 4 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Mesna MJ 10 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Methotrexate sodium 15 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Methylprednisolone UP 5 mg/mLa NCI 1.2 mg/mLa Normal inherent haze from paclitaxel decreases 1556 I
sodium succinate immediately
Metoclopramide HCl 5 mg/mL NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Mitoxantrone HCl LE 0.5 mg/mLa NCI 1.2 mg/mLa Normal inherent haze from paclitaxel decreases 1556 I
immediately
Morphine sulfate WY 1 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Nalbuphine HCl AST 10 mg/mL NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Ondansetron HCl GL 0.5 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
GL 0.03 and 0.3 BR 0.3 mg/mLa Visually compatible with no loss of either drug in 4 hr at 1741 C
mg/mLa 23 C
GL 0.03 and 0.3 BR 1.2 mg/mLa Visually compatible with no loss of either drug in 4 hr at 1741 C
mg/mLa 23 C
Ondansetron HCl with GL GL 0.3 mg/mLa 2 BR 1.2 mg/mLa Visually compatible with no loss of any drug by HPLC in 4 1741 C
ranitidine HCl mg/mLa hr at 23 C
Oxaliplatin SS 0.5 mg/mLa MJ 0.6 mg/mLa Physically compatible with no change in measured 2566 C
turbidity or increase in particle content in 4 hr at 23 C
Palonosetron HCl MGI 50 g/mL MJ 1.2 mg/mLa Physically compatible with no change in measured haze 2533 C
level or increase in particle content and little or no loss
of either drug in 4 hr
Pemetrexed disodium MJ 0.6 mg/mLa LI 20 mg/mLb Physically compatible with no change in measured 2564 C
turbidity or increase in particle content in 4 hr at 23 C
Pentostatin NCI 0.4 mg/mLb NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Potassium chloride AB 0.1 mEq/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C

Unfiled Notes Page 7

Potassium chloride AB 0.1 mEq/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Prochlorperazine 0.5 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
edisylate turbidity in 4 hr at 22 C
Propofol ZEN 10 mg/mL MJ 1.2 mg/mLa Physically compatible for 1 hr at 23 C with no increase 2066 C
in particle content
Ranitidine HCl 2 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
GL 0.5 and 2 BR 0.3 mg/mLa Visually compatible with no loss of either drug in 4 hr at 1741 C
mg/mLa 23 C
GL 0.5 and 2 BR 1.2 mg/mLa Visually compatible with no loss of either drug in 4 hr at 1741 C
mg/mLa 23 C
Sodium bicarbonate LY 1 mEq/mL NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Thiotepa IMMd 1 mg/mLa MJ 0.6 mg/mLa Physically compatible with no change in measured 1861 C
turbidity or increase in particle content in 4 hr at 23 C
TNA #218 to #226e MJ 1.2 mg/mLa Visually compatible with no precipitate or emulsion 2215 C
damage apparent in 4 hr at 23 C
Topotecan HCl SKB 56 g/mLab MJ 0.54 Visually compatible with little or no loss of either drug 2245 C
mg/mLab by HPLC in 4 hr at 22 C under fluorescent light
TPN #212 to #215 e MJ 1.2 mg/mLa Physically compatible with no change in measured 2109 C
turbidity or increase in particle content in 4 hr at 23 C
Vancomycin HCl 10 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1528 C
turbidity in 4 hr at 22 C
Vinblastine sulfate LI 0.12 mg/mLb NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Vincristine sulfate LI 0.05 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C
Zidovudine BW 4 mg/mLa NCI 1.2 mg/mLa Physically compatible with no change in measured 1556 C
turbidity in 4 hr at 22 C

aTested in dextrose 5%.

bTested in sodium chloride 0.9%.

cTested in bacteriostatic sodium chloride 0.9% preserved with benzyl alcohol 0.9%.

dLyophilized formulation tested.

eRefer to Appendix I for the composition of parenteral nutrition solutions. TNA indicates a 3 -in-1 admixture, and TPN indicates a 2-in-1 admixture.

fSodium carbonate-containing formulation tested.

Additional Compatibility Information

Infusion Solutions  The manufacturer recommends dilution of paclitaxel to a concentration between 0.3 and 1.2 mg/mL in dextrose 5%, dextrose
5% in sodium chloride 0.9%, dextrose 5% in Ringer's injection, or sodium chloride 0.9%. These solutions are stated to be phys ically and chemically
stable for up to 27 hours at room temperature (about 25 C) under normal room light. (1-2/06)

Other Information

Microbial Growth  Paclitaxel (Bristol) 0.7 mg/mL diluted in sodium chloride 0.9% did not exhibit an antimicrobial effect on the growth of three of
four organisms (Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) inoculated into the solution. S.
aureus remained viable for 4 hours. E. faecium and P. aeruginosa remained viable for 48 hours, and C. albicans remained viable to the end of the
study at 120 hours. The author recommended that diluted solutions of paclitaxel be stored under refrigeration whenever possib le and that the
potential for microbiological growth be considered when assigning expiration periods. ( 2160)

References

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

Unfiled Notes Page 8

© 2009 American Society of Health-System Pharmacists, Inc. All rights reserved.
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LAWRENCE A. TRISSEL, F.A.S.H.P.. 2009. Handbook on Injectable Drugs. Bethesda, MD. American Society of Health -System Pharmacists. ISBN-13:
978-1-58528-213-5. STAT!Ref Online Electronic Medical Library. http://online.statref.com/document.aspx?fxid=141&docid=261. 8/21/2010 3:54:55
AM CDT (UTC -05:00).
• Author:
○ LAWRENCE A. TRISSEL, F.A.S.H.P.
• Copyright:
○ © 2009 American Society of Health-System Pharmacists, Inc. All rights reserved.
• Database Title:
○ STAT!Ref Online Electronic Medical Library
• ISBN:
○ ISBN-13: 978-1-58528-213-5
• Publication City:
○ Bethesda, MD
• Publication Year:
○ 2008
• Publisher:
○ American Society of Health-System Pharmacists
• Title:
○ Handbook on Injectable Drugs - 15th Ed. (2009)
• Date Posted:
○ 11/4/2009 4:31:06 PM CDT (UTC -05:00)
• Electronic Address:
○ http://online.statref.com/document.aspx?fxid=141&docid=261
• Date Accessed:
○ 8/21/2010 3:54:55 AM CDT (UTC -05:00)
• Location In Title:
○ HANDBOOK ON INJECTABLE DRUGS - 15th Ed. (2009)
"P" Monographs
Paclitaxel - AHFS 10:00
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Unfiled Notes Page 9