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family_key=02195043&country=100
Amphotericin B
Molecular Formula: C47H73NO17

Molecular Weight: 924.11

CAS # : 1397-89-3

Synonyms: Fungizone; Amphozone; Fungilin; Ampho-Moronal

Source: Streptomyces species.

Physical Description: Yellow to orange powder. Depending on pH, amphotericin in solution is

yellow to dark yellow.

Description: An antifungal agent. This product contains no animal-derived components.

Pka values: 5.5 and 10.0.3

Solubility: Soluble in acidic water (pH 2) or basic water (pH 11) (about 0.1 mg/ml). Water
solubility can be increased with the addition of deoxycholic acid, sodium salt (increasing
solubility with increasing concentration of deoxycholic acid). Soluble in Dimethylformamide
(DMF) (2 to 4 mg/ml), DMF + 1 M HCl (3:1) (60 to 80 mg/ml), DMSO (30 to 40 mg/ml),
propylene glycol; slightly soluble in methanol and methyl alcohol; insoluble in water, anhydrous
alcohol, ether, benzene, and toluene. Solutions are stable for long periods between pH 4 and 10.1

Cat# 16723 is a concentrated solution of amphotericin at neutral to slightly basic pH,

which is slightly cloudy due to the low solubility of amphotericin in aqueous buffer.
The concentrated solution is stable at 2-8oC for up to 3 weeks. When diluted to the
working concentration (see below for recommended concentration), the amphotericin will
completely go into solution. Diluted amphotericin is stable for up to 7 days in culture at
37oC. Store diluted solutions aliquoted at -20°C or below for up to approximately 6 months.

Sterilization of solutions should be by filtration through teflon membrane filters; Amphotericin B

should not be gamma irradiated or autoclaved.

Formulation (for 16723):

Component mg/liter Mol. Wt. Mol. (mM)
Amphotericin B 0.25 924.1 0.00027
Sodium Deoxycholate 250 414.6 0.60

Description: An antimicrobial/antifungal agent effect against yeast and other fungi at a

recommended concentration of 2.5 ug/L (prepared solution use 10 ml/L). It is a mixture of
polyenes. It interrupts cell membrane permeability by binding sterols resulting in the loss of low
molecular weight compounds from the cell. Amphotericin B may be toxic to some insect cell
types. It is inactive against bacteria, rickettsia and viruses. It is typically stable in media at 37°C
in the dark for approximately 3 days.21

University of Pennsylvania Medical Center Guidelines for Antibiotic Use

Amphotericin B Deoxycholate Dosing and Administration Guidelines

Restrictions:

Use is restricted to Rhoads 6 and 7 if the dose is < 1 mg/kg/day. All other use of amphotericin B
deoxycholate requires Infectious Diseases Approval (215-306-0336).

Dosing:

Optimal dosing of amphotericin B deoxycholate for most fungal infections is not known. The
following are suggested guidelines:

Indication Dose*
Oral or esophageal candidiasis 0.1-0.3 mg/kg/day
Empiric therapy in patients with febrile neutropenia 0.5-1 mg/kg/day
Documented systemic candidiasis 0.5-1 mg/kg/day
Presumed or documented aspergillosis 1-1.5 mg/kg/day
* Note that the maximum dose of amphotericin B is 1.5 mg/kg/day

Administration:

Rationale for the following recommendations is included at the end of this document.

The following are suggested guidelines for infusion and monitoring of amphotericin B:

Infusion Guidelines:

 The preferred rate of infusion of amphotericin B deoxycholate is < 0.08 mg/kg/hour.

 If the prolonged infusion rate cannot be used routinely because of access issues, then it is
recommended that the INITIAL infusion be over 6 hours, with a subsequent shorter infusion perio
given below.

If the patient tolerates the initial 6-hour infusion, subsequent infusions may be performed over 4 hours if
necessary.
  Since the administration of normal saline has been shown in studies to reduce the risk of nephrotoxicity,
250-500 mL of normal saline should be administered prior to and following the dose of amphotericin B
deoxycholate. Note: amphotericin B deoxycholate is incompatible with saline solutions; therefore,
separate sites of administration are necessary.

Monitoring Guidelines:

 Baseline vital signs are to be taken prior to the infusion. For the first two doses of the initial treatment
course, vital signs should be recorded every 15 minutes for the first 30 minutes, then blood pressure and
temperature every hour during the infusion.

 For subsequent infusions, vital signs should be recorded every 15 minutes for the first 30 minutes, then b
pressure and temperature recorded every 2 hours during the infusion.

 The patient should be instructed to report any untoward side effects immediately. In the event of serious
symptoms, such as hypotension, cardiac arrhythmias, multiple episodes of vomiting, rash, shortness of
breath, orofacial swelling, seizures, severe rigors, and temperature greater than 38.5° C (101.3° F), the
infusion should be stopped and the physician notified. In the case of non-life-threatening adverse events (
fever, chills, rigors, nausea), the infusion may be restarted at a slower infusion rate when the symptoms
subside.

Note: If symptoms consistent with anaphylaxis/anaphylactoid reaction such as severe hypotension or

shortness of breath are observed, the infusion should not be restarted and Infectious Diseases should be
ppxcalled for advice.

Management of Infusion-related Adverse Events:

Acute infusion-related adverse reactions to amphotericin B deoxycholate are typically seen

within 90 minutes of the infusion and usually remit within 3-4 hours. The most common
reactions observed are fever with or without rigors. Tolerance to the infusion-related reactions
usually develops over time; therefore, if premedications are used early in the treatment course,
their need should be re-evaluated weekly. Consider withholding premedications after several
days if the infusion-related adverse events have resolved.

Premedication with acetaminophen and/or hydrocortisone may be given if the patient develops
fevers and rigors during the initial infusion. Meperidine may also be administered as needed for
the treatment of rigors that occur during the infusion.

Medications and Doses:

Medication Dosage
Acetaminophen 650-1000 mg 30 minutes prior to amphotericin B (nonsteroidal anti-inflammatory drugs,
oral, rectal NSAIDS, may be used if not contraindicated)
Hydrocortisone IV 25 mg initial dose prior to infusion of amphotericin B deoxycholate may be administered (if
 contraindicated) to patients who have experienced severe rigors to prior infusions of
amphotericin B. The dose of hydrocortisone may be increased to 50 mg if needed. Reassess
need every 3-7 days.
25 mg every 15 minutes as needed for rigors up to a maximum of 100 mg in 1 hour. Use wit
Meperidine IV
caution in patients with renal insufficiency.

Management of Nephrotoxicity:

Renal insufficiency (with associated electrolyte disturbances) is frequent and often stabilizes at a
creatinine of 2-3 mg/dL. Other nephrotoxic drugs such as aminoglycosides, NSAIDS, and
cisplatin can add to azotemia and should be avoided if possible. Salt repletion, by administering
250-500 mL of normal saline immediately prior to and following amphotericin B deoxycholate,
may minimize azotemia. If azotemia occurs with a serum creatinine > 2.5 mg/dL, contact
Infectious Diseases for advice. Serum creatinine and BUN should be measure initially and
periodically thereafter.

Other Adverse Effects:

 Phlebitis can occur with infusion via peripheral veins. If peripherally administered, the concentration sho
not exceed 0.1 mg/mL D5W. If phlebitis develops, decreasing the rate of infusion may help.

 Anemia - check CBC initially and periodically thereafter

 Distal renal tubular acidosis, hypokalemia, hypomagnesemia, hypocalcemia - monitor K, Mg, Ca,
bicarbonate intially and periodically thereafter

 Pulmonary infiltrates in patients receiving concomitant WBC transfusion - separate from amphotericin B
at least 6 hours

References:

1. Eriksson et al. Comparison of effects of amphotericin B deoxycholate infused over 4 or 24

hours: randomized, controlled trial. British Medical Journal 2001;322:579-82.

2. Peleg AY and Woods ML. Continuous and 4 hour infusion of amphotericin B: a comparative
study involving high-risk hematology patients. Journal of Antimicrobial Chemotherapy
2004;54:803-808.

3. Imhof A, Walter RB, and Schaffner A. Continuous infusion of escalated doses of amphotericin
B deoxycholate: an open-label observational study. Clinical Infectious Diseases 2003;36:943-51.

Rationale for Administration Guidelines:

Previous recommendations were that a test dose be administered prior to the first dose of
amphotericin B deoxycholate. However, test dosing is not always predictive of a severe reaction
to amphotericin B deoxycholate. Some patients will go on to develop a reaction to subsequent
infusions despite tolerating the test dose. In addition, test dose administration sometimes results
in delays in the administration of the full dose and/or missed doses.

Several studies have demonstrated a reduction in infusion-related adverse events and

nephrotoxicity with prolonged infusion rates of amphotericin B deoxycholate1,2. One study
demonstrated that patients who received a continuous infusion of amphotericin B deoxycholate
over 24 hours had fewer infusion-related adverse events and nephrotoxicity compared to patients
who received a standard four-hour infusion1. A second study comparing four-hour infusion rates
to a continuous infusion showed that less nephrotoxicity was observed when amphotericin B
deoxycholate was infused at a rate of < 0.08 mg/kg/hour2.

Given these data, and issues surrounding test dosing, the Antibiotic Subcommittee of the
Pharmacy and Therapeutics Committee recommends that test dosing of amphotericin B
deoxycholate NOT be performed. Instead, it is recommended to infuse the drug over a period as
long as possible (preferably at a rate of < 0.08 mg/kg/hour) with appropriate patient monitoring.

http://www.piercenet.com/products/browse.cfm?fldID=5aea3ff6-a1ed-4054-841d-42ff0097191b

Sodium
Deoxycholate 

Strong, dialyzable ionic detergent for formulation of RIPA buffers and other applications
requiring solubilization of protein or disruption of protein interactions.

Thermo Scientific Sodium Deoxycholate is an ionic detergent that is especially useful for disrupting and
dissociating protein interactions. Sodium deoxycholate (deoxycholic acid) is a water-soluble, bile-acid, ionic
detergent commonly used in protein methods. It is most frequently used as a component of cell lysis buffers (e.g.,
RIPA buffer), but also has been used for liposome preparation, isolation of membrane proteins and lipids,
preventing nonspecific binding in affinity chromatography and a cell culture media supplement.

Highlights of Sodium Deoxycholate:

 Popular anionic, bile-acid detergent for many laboratory uses

 Effective in disrupting and dissociating many types of protein interaction
 Can be removed from solution by dialysis
 Useful for elution or regeneration of certain kinds of affinity columns
 High-purity compound with low UV absorptivity
 Properties of Sodium deoxycholic acid:
 Alternative Names: Sodium deoxycholic acid;
deoxycholate, sodium salt
 Chemical Name: 3, 12-α-Dihydroxy-5β-cholan-24-
oic acid, monosodium salt
 Molecular Weight: 414.6g
 Detergent Class: Ionic (anionic)
 Aggregation Number: 5 (average)
 Micelle Molecular Weight: 2000g (average)
 Critical Micelle Concentration (CMC): 2 to 6mM (0.083 to 0.249%, w/v)
 Cloud Point: Unknown
 Dialyzable: Yes

Product Details:
Sodium Deoxycholate is the detergent recommended for stripping endotoxin (Lipopolysaccharide or LPS) from
immobilized Polymyxin B columns. This is the recommended product for use with the Thermo Scientific Detoxi-
Gel Endotoxin Removing Gel.

The effectiveness of a detergent in any application is dependent on the detergent's concentration. Too much or too
little detergent can often have a deleterious effect. It is recommended that you examine a variety of detergent
concentrations in your application. At concentrations above 2mM, cholate will form micelles having MW ~2000.
The small micelle size allows easy removal by dialysis or gel filtration when needed. Note: removal of a detergent
from a protein solution my result in protein precipitation and/or aggregation.

Specifications for Sodium Deoxycholate (Part No. 89904, 89905):

 Formula: C24H39O4Na
 Molecular Weight: 414.6g
 Purity (by HPLC): ≥98%
 Absorbance (1% Detergent Solution): 340nm <0.02; 280nm <0.04; 260nm <0.06
 pH (1% Solution): 5 to 9
 Solubility (in water at 20°C): ≥5%

http://www.ijpc.com/abstracts/abstract.cfm?ABS=482

Stability of Amphotericin B in 5% Dextrose Ophthalmic Solution

Author(s):  Peyron Florence, Elias R, Ibrahim E, Amirat-Combralier V, Bues-Charbit M,

Balansard G

Issue:  Jul/Aug 1999 - Compounding Parenteral Products

View All Articles in Issue

Abstract:  The stability of amphotericin B 5 mg/mL in 5% dextrose ophthalmic solution

prepared by the Hospital Pharmacy Service was studied in different conditions of storage and
use. Admixtures of amphotericin B were aseptically prepared in low-density polyethylene
dropper bottles. The stability of amphotericin B was evaluated in ophthalmic dropper bottles
stored in a refrigerator, at room temperature, protected from, or exposed to, light. To simulate the
effect of exposure to air, some ophthalmic dropper bottles were opened twice daily and two
drops were removed. Immediately after preparation, samples were collected to determine the
initial drug concentration by high-performance liquid chromatography and to assess pH,
osmolality and sterility. The same tests were conducted after four, eight and 15 days of storage in
ophthalmic containers opened daily and unopened after eight, 15, 30, 60, 75 and 120 days of
storage. Samples were visually inspected daily for signs of physical incompatibility. An
additional study was conducted in four ophthalmic containers collected in the ophthalmology
unit after eight or 15 days of current patient use testing the same parameters. Ophthalmic
containers stored in the refrigerator (the closed and the opened daily set) showed no loss or
deterioration of amphotericin B during the corresponding period of storage (120 and 15 days,
respectively). We observed precipitation and degradation after 13 days of storage in ophthalmic
containers exposed to normal lighting conditions at room temperature, and after 16 days in
ophthalmic containers protected from light. There was no appreciable change in pH or osmolality
in any of the samples. Microbiological investigation disclosed negative culture results for all
samples. This study shows that aseptically prepared amphotericin B ophthalmic solution
packaged in low-density polyethylene bottles can be stored safely for up to 120 days when
unopened and stored at 4°C and protected from light, for 16 days when stored at 22°C and
protected from light and for 13 days when stored at 22°C and exposed to light.