Vancomycin

1449.25

1447.4302

215-772-6

DTXSID0042664

3004209090

531

4.73460

Almost white powder

1.2882 (rough estimate)

1.7350 (estimate)

White solid; solubility in water: greater than 100 mg/mL; moderately soluble in methanol; insoluble in higher alcohols, acetone, ether; UV max absorption (water): 282 nm (e = 40, 1%, 1 cm) /Vancomycin hydrochloride/

Store in a tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. Store in a freezer. /Vancomycin hydrochloride/|Commercially available vancomycin hydrochloride capsules and powder for IV administration should be stored at 15 - 30 °C.

pka1 = 2.6; pKa2 = 7.2; pKa3 = 8.6; pKa4 = 9.6; pKa5 = 10.5; pKa6 = 11.7

Tan to brown powder; odorless; bitter taste. Soluble in water; moderately soluble in dilute methanol; insoluble in higher alcohols, acetone, ether /Vancomycin hydrochloride/|ISOELECTRIC POINT: APPROX PH 5 /HYDROCHLORIDE/

When reconstituted with sterile water for injection, vancomycin hydrochloride injection is stable for 2 weeks at room temperature; the manufacturers state that reconstituted injections may be stored for 96 hours at 2 - 8 °C without substantial loss of potency. When reconstituted as directed in 0.9% sodium chloride injection or 5% dextrose injection, solutions prepared from ADD-Vantage vials of the drug are stable for 24 hours at room temperature. Vancomycin solutions containing 5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection are reportedly stable for at least 17 days when stored at 24 °C in glass or PVC containers and for at least 63 days when stored at 5 °C or -10 °C in glass containers. Following reconstitution with sterile water for injection as directed, vancomycin solutions that have been further diluted to a concentration of 5 mg/mL in 5 - 30% dextrose injection are stable when stored in plastic syringes for 24 hours at 4 eg C and then subsequently for 2 hours at room temperature.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including vancomycin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Vancomycin hydrochloride/

|Danger|H334 (92.68%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]|P261, P285, P304+P341, P342+P311, and P501|Aggregated GHS information provided by 42 companies from 4 notifications to the ECHA C&L Inventory.

Gloves: Chemically compatible. Eye protection: Safety goggles or glasses. Protective clothing: Protect exposed skin. /Vancomycin hydrochloride/|Use a NIOSH approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used. /Vancomycin hydrochloride/

This material is assumed to be combustible. /Vancomycin hydrochloride/

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing. /Vancomycin hydrochloride/|Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials. /Vancomycin hydrochloride/

This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity. /Vancomycin hydrochloride/

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately-labeled container for disposal. Wash spill site. /Vancomycin hydrochloride/

Engineering controls such as exhaust ventilation are recommended. /Vancomycin hydrochloride/|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling. /Vancomycin hydrochloride/|SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Eye, skin, ... and/or respiratory tract irritation. /Vancomycin hydrochloride/

Intravenous vancomycin is associated with minor, transient and asymptomatic elevations in serum aminotransferase levels in 1% to 5% of patients, but similar or minimally lower rates of abnormalities are usually reported with comparative agents. In rare instances, the serum enzyme elevations are more marked and may be associated with mild symptoms, although usually without jaundice. In recent years, vancomycin has been linked to hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and the distinctive syndrome of drug reaction, eosinophilia and systemic symptoms (DRESS). These forms of hypersensitivity generally arise within a few days to 3 to 4 weeks after initiation of intravenous (iv) vancomycin therapy. Fever and severe skin rash generally dominate the clinical presentation, but systemic symptoms can include renal, respiratory or heart failure, neutropenia, thrombocytopenia, and liver injury. Cases of DRESS syndrome associated with vancomycin are often accompanied by serum enzyme elevations (Case 1), but marked elevations, symptoms and jaundice are uncommon. The usual systemic features of vancomycin induced DRESS syndrome are renal rather than liver injury but features of hypersensitivity are usually more prominent than organ-specific injury. Nevertheless, in rare instances the liver injury can be severe (Case 2) and result in hepatic failure and death. Patients who receive intravenous vancomycin often have multiple comorbidities including sepsis and receive multiple antibiotics which make the attribution of the hypersensitivity reactions and liver injury with vancomycin difficult. Other more well-known causes of DRESS syndrome include allopurinol, sulfonamides, and the aromatic anticonvulsants. These other causes of DRESS syndrome are more likely to be associated with clinically apparent and even fatal liver injury.|In prelicensure controlled trials, serum ALT elevations during therapy with dalbvancin, oritavancin or telavancin were common, occurring in up to 25% of patients. Serum aminotransferase elevations above three times the upper limit of normal, however, were uncommon, occurring in 0.8% to 6% of patients receiving dalbavancin, oritavancin or telavancin. Furthermore, these rates of liver test abnormalities were not very different from those in comparator arms. The ALT elevations during glycopeptide antibiotic therapy were in general transient, asymptomatic and only mild-to-moderate in severity, rarely leading to dose modifications or early discontinuations. There were no reports of clinically apparent liver injury with jaundice in the registration trials of these agents. Since their approval and more wide scale use, there have been no published reports of liver injury attributed to glycopeptide antibiotics, although hypersensitivity reactions have been reported which can sometimes be associated with a mild-to-moderate degree of liver injury. Regardless, these three agents are relatively new, have not been widely used and when used, are given for a relatively short period of time and none have been linked to serious cases of liver injury.

Concomitant use of vancomycin and anesthetic agents has been associated with anaphylactoid reactions and an increased frequency of infusion reactions (e.g., hypotension, flushing, erythema, urticaria, pruritus). Erythema and histamine-like flushing has occurred in pediatric patients receiving vancomycin and anesthetic agents concomitantly. The risk of infusion-related adverse effects may be minimized if vancomycin is given as a 1-hour IV infusion prior to induction of anesthesia.|In vitro, the antibacterial effects of vancomycin and aminoglycosides are synergistic against many strains of Staphylococcus aureus, nonenterococcal group D streptococci (Streptococcus bovis), enterococci (Enterococcus faecalis), and viridans streptococci. However, concomitant use of vancomycin and aminoglycosides is associated with an increased risk of ototoxicity and/or nephrotoxicity.|Because of the possibility of additive toxicities, the concurrent or sequential systemic or topical use of other ototoxic and/or nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, bacitracin, cisplatin, colistin, polymyxin B) and vancomycin requires careful serial monitoring of renal and auditory function. These drugs should be used with caution in patients receiving vancomycin therapy.|Renal failure developed after a prolonged course of vancomycin therapy in 2 patients who were receiving tenofovir disoproxil fumarate as part of an antiretroviral regimen. Tenofovir has been implicated in the development of Fanconi syndrome and renal insufficiency because of its effects on the proximal renal tubule. Vancomycin nephrotoxicity is infrequent but may result from coadministration with a nephrotoxic agent. Clinicians should be aware that tenofovir may raise the risk of renal failure during prolonged administration of vancomycin.|For more Interactions (Complete) data for Vancomycin (6 total), please visit the HSDB record page.

LD50 Mouse oral 5000 mg/kg /Monohydrochloride/|LD50 Mouse ip 1734 mg/kg|LD50 Mouse iv 430 mg/kg|LD50 Mouse sc 5000 mg/kg|LD50 Rat iv 319 mg/kg

Produced by Streptomyces orientalis from Indonesian and Indian soil /Vancomycin hydrochloride/

Vancomycin is distributed into milk following IV administration. Systemic absorption of oral vancomycin is very low and it is not known whether the drug distributes into human milk following oral administration.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 14,913 workers (13,290 of these were female) were potentially exposed to vancomycin in the US(1).

The glycopeptide antibiotics are semisynthetic macromolecules that are structurally related to vancomycin and have antibacterial activity against several gram positive organisms including methicillin resistant Staphylococcus aureus (MRSA). Three lipoglycopeptide antibiotics are available for use in the United States: dalbavancin, oritavancin and telavancin. All three agents have been associated with transient serum enzyme elevations during therapy, but they have yet to be linked convincingly to cases of clinically apparent acute liver injury.

Antiinfective Agents|Antineoplastic Agents

Antibiotics, Glycopeptide|Vancomycin hydrochloride is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci. It is indicated for penicillin-allergic patients, for patients who cannot receive or who have failed to respond to other drugs, including the penicillins or cephalosporins, and for infections caused by vancomycin-susceptible organisms that are resistant to other antimicrobial drugs. Vancomycin hydrochloride is indicated for initial therapy when methicillin-resistant staphylococci are suspected, but after susceptibility data are available, therapy should be adjusted accordingly. /Included in US product label/|Vancomycin hydrochloride is effective in the treatment of staphylococcal endocarditis. Its effectiveness has been documented in other infections due to staphylococci, including septicemia, bone infections, lower respiratory tract infections, skin and skin-structure infections. When staphylococcal infections are localized and purulent, antibiotics are used as adjuncts to appropriate surgical measures. /Included in US product label/|The parenteral form of vancomycin hydrochloride may be administered orally for treatment of antibiotic-associated pseudomembranous colitis produced by C. difficile and for staphylococcal enterocolitis. Parenteral administration of vancomycin hydrochloride alone is of unproven benefit for these indications. Vancomycin hydrochloride is not effective by the oral route for other types of infection. /Included in US product label/|For more Therapeutic Uses (Complete) data for Vancomycin (12 total), please visit the HSDB record page.

Ototoxicity and nephrotoxicity are the most serious adverse effects of parenteral vancomycin therapy. The incidences of ototoxicity and nephrotoxicity have not been well established, but clinical experience to date suggests that these adverse effects occur relatively infrequently. Ototoxicity and nephrotoxicity are most likely to occur in patients with renal impairment, patients receiving IV vancomycin in high doses or for prolonged periods, or patients receiving other ototoxic and/or nephrotoxic drugs. Although ototoxicity and nephrotoxicity have been associated with serum or blood vancomycin concentrations of 80-100 ug/mL, these reactions have occurred with concentrations as low as 25 ug/mL. Correlations between serum vancomycin concentrations and ototoxicity and nephrotoxicity still remain to be clarified. Ototoxicity may be transient or permanent. Vancomycin may cause damage to the auditory branch of the eighth cranial nerve and permanent deafness has occurred. Vertigo, dizziness, and tinnitus have been reported rarely. Tinnitus may precede the onset of deafness and necessitates discontinuance of the drug. Deafness may progress despite cessation of vancomycin therapy. Vancomycin-induced nephrotoxicity may be manifested by transient elevations in BUN or serum creatinine concentrations, and the presence of hyaline and granular casts and albumin in the urine. Fatal uremia has occurred. Rarely, the drug has been associated with acute interstitial nephritis.|Rapid IV administration of vancomycin has resulted in a hypotensive reaction frequently referred to as the "red-man syndrome" or "red-neck syndrome". The reaction is characterized by a sudden decrease in blood pressure which can be severe and may be accompanied by flushing and/or a maculopapular or erythematous rash on the face, neck, chest, and upper extremities; the latter manifestations may also occur in the absence of hypotension. Wheezing, dyspnea, angioedema, urticaria, and pruritus may also occur. Rarely, cardiac arrest or seizures have occurred. Vancomycin-induced hypotension appears to result from a negative inotropic and vasodilating action produced in part by a release of histamine, which is directly related to the rate of infusion; the release of histamine also appears to be responsible for the usual manifestations (e.g., erythema, rash, pruritus) of the "red" characterization. The reaction usually begins a few minutes after the vancomycin infusion is started, but may not occur until after the infusion is completed, and usually resolves spontaneously over one to several hours after discontinuance of the infusion. If the hypotensive reaction is severe, the use of antihistamines, corticosteroids, or IV fluids may be necessary. The hypotensive reaction is related to the rate of infusion of vancomycin and has been reported most frequently when the drug was administered over a period of 10 minutes or less; however, the reaction may also occur rarely when the drug is infused over a period of 1 hour or longer. To minimize the risk of a hypotensive reaction, vancomycin should be infused over a period of at least 1 hour and the patient's blood pressure should be monitored during the infusion. In patients who have had the reaction, subsequent doses of vancomycin can usually be given without adverse effect if administered at a slow rate (e.g., over several hours). Pretreatment with antihistamines may be of benefit. If attempts to minimize the reaction fail, use of another anti-infective agent may be necessary. The reaction reportedly has occurred in more than 50% of healthy individuals given vancomycin but less frequently when the drug is used therapeutically.|Urticaria, exfoliative dermatitis, macular rashes, eosinophilia, vasculitis, a shock-like state, transient anaphylaxis, and, occasionally, vascular collapse have been reported in patients receiving vancomycin. The drug also has been associated with Stevens-Johnson syndrome in at least one patient.|A throbbing pain in the muscles of the back and neck has been reported with vancomycin and can usually be minimized or avoided by slower administration of the drug. In patients undergoing continuous ambulatory peritoneal dialysis (CAPD), intraperitoneal administration of vancomycin has been associated with chemical peritonitis, a syndrome consisting of a cloudy dialysate, which may be accompanied by abdominal pain and fever. Chemical peritonitis usually disappears shortly after discontinuance of intraperitoneal vancomycin. Other adverse effects of vancomycin include chills and fever. Priapism after a second IV dose of vancomycin, with recurrence on inadvertent rechallenge, occurred in a 37-year-old man with severe underlying diabetes mellitus; bilateral phlebotomy of the corpus cavernosum resulted in resolution of the priapism.|For more Drug Warnings (Complete) data for Vancomycin (22 total), please visit the HSDB record page.

Vancomycin hydrochloride is not appreciably absorbed from the GI tract in most patients and must be given parenterally for the treatment of systemic infections. Oral bioavailability usually is less than 5%; however, limited data suggest that clinically important serum concentrations of the drug may result following enteral or oral administration of vancomycin in some patients with colitis and/or in those with renal impairment.|In adults with normal renal function who received multiple 1 g doses of vancomycin (15 mg/kg) given by IV infusion over 1 hour, mean plasma concentrations immediately after completion of the infusion are approximately 63 ug/mL and mean plasma concentrations 2 and 11 hours later are approximately 23 or 8 ug/mL, respectively. When multiple 500-mg doses are given by IV infusion over 30 minutes, mean plasma concentrations are about 49 ug/mL immediately following the infusion and about 10 ug/mL 6 hours after infusion.|Vancomycin is distributed into milk following IV administration. Systemic absorption of oral vancomycin is very low and it is not known whether the drug distributes into human milk following oral administration.|Vancomycin readily crosses the placenta and is distributed into cord blood.|Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mcg/mL. After IV administration of vancomycin hydrochloride, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin hydrochloride does not readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs.

The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function.|In anephric patients, the average half-life of elimination is 7.5 days.

Vancomycin is bactericidal and appears to bind to the bacterial cell wall causing blockage of glycopeptide polymerization. This effect, which occurs at a site different from that affected by the penicillins, produces immediate inhibition of cell wall synthesis and secondary damage to the cytoplasmic membrane. Magnesium, manganese, calcium, and ferrous ions reduce the degree of adsorption of vancomycin to the cell wall, but the in vivo importance of this interaction is unknown.|The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis.

Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. Hemofiltration and hemoperfusion with polysulfone resin have been reported to result in increased vancomycin clearance.|Decontamination: Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antibacterial agents/|Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. Replace fluid losses resulting from gastroenteritis with intravenous crystalloids. ... /Antibacterial agents/|Enhanced elimination: Most antibiotics are excreted unchanged in the urine, so maintenance of adequate urine flow is important. The role of forced diuresis in unclear. Hemodialysis is not usually indicated, except perhaps in patients with renal dysfunction and a high level of a toxic agent. /Antibacterial agents/|For more Antidote and Emergency Treatment (Complete) data for Vancomycin (7 total), please visit the HSDB record page.

Antibiotic-associated pseudomembranous colitis, caused by toxin-producing clostridia (e.g., C. difficile), has been reported with the use of nearly all anti-infectives, including IV vancomycin, and should be considered in the differential diagnosis of patients who present with diarrhea subsequent to administration of anti-infectives. Pseudomembranous colitis may occur during or following discontinuance of anti-infective therapy and ranges in severity from mild to life-threatening. Mild cases of colitis may respond to discontinuance of the drug alone, but diagnosis and management of moderate to severe cases should include appropriate bacteriologic studies and treatment with fluid, electrolyte, and protein supplementation as indicated. If colitis is moderate to severe and is not relieved by discontinuance of the drug, appropriate anti-infective therapy (e.g., metronidazole) should be administered. Nausea also has been reported in patients receiving vancomycin therapy.|Urticaria, exfoliative dermatitis, macular rashes, eosinophilia, vasculitis, a shock-like state, transient anaphylaxis, and, occasionally, vascular collapse have been reported in patients receiving vancomycin. The drug also has been associated with Stevens-Johnson syndrome in at least one patient.|/CASE REPORTS/ A 60-year-old man with a history of hypertension, congestive heart failure and dyslipidemia was admitted for a right shoulder rotator cuff tear. He underwent right-shoulder arthroscopy and rotator cuff repair. About three weeks later, he developed pain, swelling and purulent drainage from his right shoulder. Arthroscopic irrigation and drainage was then performed. Intraoperative fluid revealed the presence of Methicillin susceptible Staphylococcus aureus, vancomycin-sensitive Enterococcus spp. and Serratia marcescens. The patient had no known allergies. After reviewing his antimicrobial susceptibility, he was started on vancomycin 1500 mg intravenously every 12 hours (to treat both Staphylococcus aureus and Enterococcus spp) and ciprofloxacin 750 mgs by oral induction every 12 hours. The patient's condition improved following antibiotic treatment. He was discharged and allowed to go home on IV vancomycin and oral ciprofloxacin. The patient's platelet count on the day of starting vancomycin therapy was 253 x 10(3)/cu mm. At weeks one, two and three, the counts were 231 x 10(3)/cu mm, 272 x 10(3)/mm and 6 x 103/cu mm, respectively. The patient was admitted for further work-up of the thrombocytopenia. He was later shown to have vancomycin-induced platelet-reactive antibodies, causing significant thrombocytopenia, and then reversal after his vancomycin medication was discontinued. Thrombocytopenia is a potentially life-threatening condition. Vancomycin is often clinically overlooked as a cause of thrombocytopenia, especially in a scenario of sepsis or when there is use of heparin. Simple laboratory testing with drug-dependent antibodies can be helpful in identifying vancomycin as a cause of thrombocytopenia.|/CASE REPORTS/ A 70-year-old man receiving vancomycin for a methicillin-resistant Staphylococcus aureus abscess developed a drug-induced hypersensitivity reaction with rash, eosinophilia, and acute renal failure requiring dialysis. Renal biopsy revealed diffuse and marked interstitial and tubular infiltration by mononuclear cells and eosinophils; acute tubulointerstitial nephritis was diagnosed. The rash progressed to erythema multiforme major after rechallenge with vancomycin in the setting of methicillin-resistant Staphylococcus aureus peritoneal catheter-related peritonitis and then to fatal toxic epidermal necrolysis in the setting of steroid taper and persistent serum vancomycin levels. This case further implicates vancomycin as a drug that infrequently can cause severe acute tubulointerstitial nephritis and exfoliative dermatitis. When a renally excreted drug such as vancomycin is administered, serum drug levels should be serially monitored and high-dosage steroids be maintained or tapered slowly until serum drug levels become undetectable.|/CASE REPORTS/ Disseminated rash and pruritus are described in an 82-year-old woman with chronic renal failure following administration of oral vancomycin hydrochloride 125 mg q6h for the treatment of Clostridium difficile colitis. Renal function was estimated to be 0.27 mL/s based on a serum creatinine of 177 mumol/L. After eight days of therapy, she developed a slightly raised maculopapular rash on her legs and torso, which spread to her abdomen and arms with continued treatment. Vancomycin was discontinued and the patient was treated symptomatically. The rash cleared and did not recur. Rechallenge with vancomycin was not initiated. No other changes in medications or initiations of new medications occurred during the time of treatment with vancomycin. The patient denied any previous immunologically mediated reactions to medications. Maculopapular rash is rare secondary to vancomycin administration, particularly after oral administration. Although clinically significant serum concentrations can be obtained in patients treated with oral vancomycin who have concomitant C. difficile colitis and renal failure, there has not been a clear correlation between these concentrations and any reported adverse sequelae. This case supports the possible occurrence of a true allergic reaction secondary to low-dose oral vancomycin administration.

Table: Vancomycin Hydrochloride Preparations [Table#4522]|Grade: USP /Vancomycin hydrochloride/|Parenteral, Injection (frozen), for IV infusion 5 mg (of vancomycin) per mL (500 mg) in 5% Dextrose, Vancocin HCl in Iso-osmotic Dextrose Injection (Lilly)

Potency: equivalent to not less than 900 ug of vancomycin per mg. /Vancomycin hydrochloride/|The content of a 10-g container ... is mixed with 115 mL of distilled water, so that each 6-mL portion provides approx 500 mg of the drug. /Hydrochloride/

THIS REVERSE PHASE, HIGH PRESSURE LIQUID CHROMATOGRAPHIC METHOD APPLIES TO DETERMINATION OF THESE COMPOUNDS IN ANTIBIOTIC MIXTURES.