Vancomycin Hydrochloride Capsules - Scientific Information
|Manufacture:||Fresenius Kabi USA, LLC|
|Condition:||Bacteremia, Bacterial Endocarditis Prevention (Bacterial Endocarditis Prophylaxis), Bacterial Infection, Bone infection (Osteomyelitis), Methicillin-Resistant Staphylococcus Aureus Infection, Pneumonia, Sepsis, Skin or Soft Tissue Infection, Surgical Prophylaxis|
|Trade Name:||Vancomycin Hydrochloride Capsules, USP|
|Proper Name:||Vancomycin hydrochloride|
|Chemical Name:||(Sa)-(3S,6R,7R,22R,23S,26S,36R,38aR)-44-[[2-0-(3-Amino-2,3, 6-trideoxy-3-C-methyl-α-L-lyxo-hexopyranosyl)-β-D-glucopyranosyl] oxy]-3-(carbamoylmethyl)-10,19-dichloro-2,3,4,5,6,7,23,24, 25,26,36,37,38,38a-tetradecahydro-7,22,28,30,32-pentahydroxy-6-[(2R)-4-methyl-2-(methylamino)valeramido]-2,5,24,38,39-pentaoxo-22H-8,11:18,21-dietheno-23,36-(iminomethano)-13,16:31,35-dimetheno-1H,16H-[1,6,9]oxadiazacyclohexadecino[4,5-m][10,2,16] - benzoxadiazacyclo-tetracosine-26, carboxylic acid, monohydrochloride|
|Description:||Vancomycin hydrochloride is a chromatographically purified tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis (formerly Nocardia orientalis). It is an off-white free flowing powder, having essentially no odor. It is soluble in water and insoluble in organic solvents.|
Vancomycin Hydrochloride Capsules, USP contain vancomycin hydrochloride, (expressed in terms of free base) and Polyethylene Glycol 6000. The capsules also contain FD&C Blue No.2, gelatin, iron oxide, polyethylene glycol, and titanium dioxide.
Stability and Storage Recommendations
Store at controlled temperature of 15°C to 25°C. Protect from moisture. Keep out of reach of children.
Availability of Dosage Forms
Vancomycin Hydrochloride Capsules, USP capsules equivalent to 125 mg (0.08 mmol) vancomycin and 250 mg (0.17 mmol) vancomycin are available in (unit-dose) packages of 20 capsules.
Vancomycin Hydrochloride Capsules, USP 125 mg: A size 2, grey/light grey hard gelatin capsule with a white to slightly red or slightly brown solid mass.
Vancomycin Hydrochloride Capsules, USP 250 mg: A size 0, green/turquoise hard gelatin capsule with a white to slightly red or slightly brown solid mass.
Cross-resistance has not been demonstrated between vancomycin hydrochloride and other classes of antibiotics. Laboratory-induced resistance has been reported to occur in a slow stepwise fashion. The development of resistance to vancomycin by staphylococci has not been reported in clinical use. Its activity is not significantly altered by changes in pH or by the presence of serum. Vancomycin is active against most strains of the following organisms invitro and in clinical infections:
Staphylococcus aureus (including heterogeneous methicillin-resistant strains)
S. epidermidis (including heterogeneous methicillin-resistant strains)
Streptococcus pneumoniae (including multiple-resistant strains)
S. pyogenes (group A beta-hemolytic)
S. agalactiae (group B beta-hemolytic)
Alpha-hemolytic streptococci (viridans groups)
Enterococci (e.g., E. faecalis)
Note: Many strains of streptococci, staphylococci, C. difficile, and other gram- positive bacteria are susceptible in vitro to concentrations of 0.5 to 5 μg/mL. Staphylococci are generally susceptible to less than 5 μg/mL of vancomycin hydrochloride, but a small proportion of S.aureus strains requires 10 to 20 μg/mL for inhibition.
In vitro resistance to vancomycin has been reported among some enterococcal and staphylococcal isolates.
Vancomycin is not effective in vitro against gram-negative bacilli, mycobacteria, or fungi.
|Organism||No. of Strains||MIC (µg/mL)|
|Staphylococcus aureus||55||1.0 – 2.0||1.0|
|101||0.78 – 12.5||3.1|
|35||0.25 – 1.0||1.0|
|Staphylococcus aureus (methicillin-resistant)||22||0.5 – 4.0||0.5|
|38||0.3 – 12.0||1.5|
|12||0.2 – 3.12||0.4|
|Streptococcus epidermidis||177||1.56 – 6.25||3.1|
|35||0.4 – 3.1||1.6|
|27||0.2 – 6.25||3.12|
|Streptococcus pneumoniae||70||0.125 – 0.5||0.25|
|Streptococcus pyogenes||12||0.8 – 3.1||1.6|
|Streptococcus viridans||82||0.39 – 1.56||0.78|
|Streptococcus group D Enterococci||382||0.8 → 100.0||3.1|
|Clostridium perfringens||43||0.4 – 1.6||0.8|
|Clostridium ramosum||49||3.1 – 12.5||6.2|
|Clostridium difficile||14||< 1.0||< 1.0|
|78||1.0 – 4.0|
Methods of Susceptibility Testing
When the standardized method of disc susceptibility testing is used, a 30 µg disc of vancomycin should produce a zone of more than 11 mm when in contact with "susceptible" organisms. A zone size of 10 - 11 mm indicates intermediate susceptibility, while a zone size of 9 mm or less indicates resistance.
With the WHO-ICS agar dilution and broth dilution methods, an MIC of ≤ 5 μg/mL indicates susceptibility to vancomycin.
Vancomycin serum and tissue levels may be determined by Bennett's agar-well diffusion method. This test can quantitatively measure vancomycin concentrations from 0.5 to 8 µg/mL.
Two disc-diffusion assay methods are available for vancomycin. Both use Bacillus subtilis as the test organism. The first method, which uses antibiotic medium No. 5, is capable of measuring vancomycin levels from approximately 5 to 40 μg/mL. The second uses minimal salt agar and is capable of detecting vancomycin concentrations from about 0.8 to 25 μg/mL. A modification of this assay permits reliable bioassay for vancomycin (in concentrations of 0.78 to 50.0 μg/mL) in the presence of rifampin or aminoglycosides. Two commercially prepared assay methods are now available and include a radioimmunoassay and an automated fluorescence polarization immunoassay.
Infusions of 1 g vancomycin in 250 mL D5W were given over 30 minutes to 29 anephric patients. After 18 days with intermittent dialysis at three -day intervals, the serum concentration was still 3.5 μg/mL. The elimination half-life was about 7.5 days.
Vancomycin is poorly absorbed after oral administration, only trace amounts being found in blood or urine. Following 125 mg orally 4 times daily, the mean concentration of vancomycin in stools was approximately 350 μg/g. Following up to ten daily oral doses of 2 g, a mean level of 3100 μg/g with a range of 905 - 8760 μg/g was detected in feces of patients with pseudomembranous colitis.
Tissue Penetration and Distribution
Central Nervous System
Vancomycin does not readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs.
Other Tissues and Fluids
Vancomycin concentration in human pericardial, pleural, bile, ascitic and synovial fluids reaches approximately one third of the equivalent serum level after single intravenous doses. A level of 7.6 μg/mL was achieved in the brain cyst of one infant following intravenous infusion of 40 mg/kg daily for 4 days.
Vancomycin was administered to mice, rats and dogs by various routes.
|Route of Administration||Rat||Mouse||Dog|
|Intravenous||319 ± 14||489 ± 41||292 ± 29|
|Intraperitoneal||2218 ± 240||1734 ± 227|
Rats died quickly from CNS-mediated effects, while dogs died, generally from kidney failure, several days after the intravenous administration.
Vancomycin, when administered intravenously in a 5 percent solution to dogs at a rate of
0.6 mL/minute, caused a slight dose-related drop in blood pressure. When the same dogs were given the same doses at a rate of 15 mL/minute, blood pressure dropped dramatically, as much as 40 percent. Whether the response is due to a direct effect on histamine receptors or to release of histamine, possibly from mast cells, is not known.
Dogs were given daily i.v. doses of vancomycin at 12.5 mg and 50 mg/kg for 21 - 311 days. Renal damage was seen in 4/22 dogs receiving 50 mg/kg/day.
Monkeys tolerated i.v. doses of 25 and 50 mg/kg/day for 16 - 187 days, with irritation at the injection site as the only toxic effect.
Cats received i.v. doses of 25 and 50 mg/kg/day for three months with no systemic toxicity.
Anaphylaxis could not be induced in 9 guinea pigs that received 100 mg vancomycin subcutaneously when challenged by a 25 mg i.v. dose, 25 days later.
Intraperitoneal doses of 150 mg vancomycin or 60 mg tobramycin given subcutaneously to rats, resulted in no nephrotoxicity; however, when administered together, significant renal toxicity occurred.
Vancomycin 1000 mg/kg administered subcutaneously concurrently with ethacrynic acid 40 mg/kg intravenously, did not produce ototoxicity in a guinea pig model.
Neuromuscular blocking has not been demonstrated in vancomycin-treated rabbits.