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{{Drugbox|
{{DrugProjectFormSinglePage
|IUPAC_name = unable to be assigned
|authorTag={{AJ}}
| width=300px
|genericName=Vancomycin hydrochloride
| image=Vancomycin.png
|aOrAn=a
| CAS_number=1404-90-6
|drugClass=[[glycopeptide]], [[antibiotics]]
| ATC_prefix=A07
|indicationType=treatment
| ATC_suffix=AA09
|indication=[[C. difficile|C. difficile-associated diarrhea]], [[enterocolitis]] caused by [[Staphylococcus aureus]] (including [[methicillin]]-resistant [[strains]])
| ATC_supplemental={{ATC|J01|XA01}}
|adverseReactions=[[nausea]], [[vomiting]], [[abdominal pain]], [[diarrhea]], and [[hypokalemia]]
| PubChem=14969
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
| DrugBank=APRD01287
|blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
| C=66 | H=75 | Cl=2 | N=9 | O=24
 
| molecular_weight = 1449.3 g.mol<sup>-1</sup>
* Content
| bioavailability= Negligible (oral)
 
| metabolism = Excreted unchanged
<!--Adult Indications and Dosage-->
| elimination_half-life=4–11 hours <small>(adults)</small><br />6-10 days <small>(adults, impaired renal function)</small>
 
| excretion = Renal
<!--FDA-Labeled Indications and Dosage (Adult)-->
| pregnancy_category = B2 <small>([[Australia|Au]])</small>, B <small>([[United States|U.S.]])</small>
|fdaLIADAdult=
| legal_status = S4 <small>(Au)</small>, POM <small>([[United Kingdom|UK]])</small>, ℞-only <small>(U.S.)</small>
* Vancomycin CAPSULES are indicated for the treatment of [[C. difficile|C. difficile-associated diarrhea]]. Vancomycin CAPSULES are also used for the treatment of [[enterocolitis]]  caused by [[Staphylococcus aureus]] (including [[methicillin]]-resistant strains). [[Parenteral]] administration of vancomycin is not effective for the above [[infections]]; therefore, Vancomycin CAPSULES must be given orally for these [[infections]].
| routes_of_administration= [[intravenous|IV]], oral
 
}}
* Orally administered Vancomycin is not effective for other types of [[infections]].
{{SI}}
 
{{CMG}}
* To reduce the development of [[drug-resistant]] [[bacteria]]  and maintain the effectiveness of Vancomycin CAPSULES and other [[antibacterial]]  drugs, Vancomycin CAPSULES should be used only to treat [[infection]]s that are proven or strongly suspected to be caused by susceptible [[bacteria]]. When [[culture]] and susceptibility information are available, they should be considered in selecting or modifying [[antibacterial]]  therapy. In the absence of such data, local [[epidemiology]] and [[susceptibility]] patterns may contribute to the empiric selection of therapy.
__NOTOC__
 
==Overview==
=====Dosing Information=====
[[Image:Vancomysin AntimicrobAgentsChemother 1990 1342.jpg|thumbnail|300px|Crystal structure of a short peptide L-Lys-D-Ala-D-Ala (bacterial cell wall precursor, in green) bound to vancomycin (blue) through hydrogen bonds. Reported by Knox and Pratt in Antimicrob. Agents. Chemother., 1990 1342-1347]]
 
'''Vancomycin''' ([[International Nonproprietary Name|INN]]) ({{pronEng|ˌvæŋkoʊˈmaɪs<s>ɪ</s>n}}) is a [[glycopeptide]] [[antibiotic]] used in the [[prophylaxis]] and treatment of infections caused by [[Gram-positive]] [[bacterium|bacteria]]. It has traditionally been reserved as a [[drug of last resort|drug of "last resort"]], used only after treatment with other antibiotics had failed, although the emergence of vancomycin-resistant organisms means that it is increasingly being displaced from this role by [[linezolid]] and the [[carbapenem]]s.
* Vancomycin CAPSULES are used in treating [[C. difficile|C. difficile-associated diarrhea]] and [[staphylococcal]] [[enterocolitis]] .
==History==
 
Vancomycin was first isolated by [[EC Kornfeld]] (working at [[Eli Lilly and Company|Eli Lilly]]) from a soil sample collected from the interior jungles of [[Borneo]] by a missionary. The organism that produced it was eventually named ''[[Amycolatopsis orientalis]]''.<ref> {{cite journal|author=Levine DP|title=Vancomycin: a history|journal=Clin Infect Dis|year=2006|volume=42|issue=Suppl 1|pages=S5&ndash;12|doi=10.1086/491709}}</ref> The original indication for vancomycin was for the treatment of [[penicillin]]-resistant ''[[Staphylococcus aureus]]''.<ref name="Moellering2006">{{cite journal | author=Moellering, RC Jr. | title=Vancomycin: A 50-Year Reassessment | journal=Clin Infect Dis | year=2006 | volume=42 | pages=S3&ndash;S4 | pmid=16323117 }}</ref><ref name="Levine2006">{{cite journal | author=Donald P. | title=Vancomycin: A History | journal=Clin Infect Dis | year=2006 | volume=42| pages=S5-S12 | pmid=16323120 }}</ref>
* [[C. difficile|C. difficile-associated diarrhea]]: The recommended dose is 125 mg administered orally 4 times daily for 10 days.
* [[Staphylococcal]] [[enterocolitis]]: Total daily dosage is 500 mg to 2 g administered orally in 3 or 4 divided doses for 7 to 10 days.
|offLabelAdultNoGuideSupport=
* [[bacterial meningitis]]
* [[Peritoneal dialysis]]-associated [[peritonitis]]
 
<!--FDA-Labeled Indications and Dosage (pediatric )-->
|fdaLIADPed=* The usual daily dosage is 40 mg/kg in 3 or 4 divided doses for 7 to 10 days. The total daily dosage should not exceed 2 g.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Vancomycin in [[pediatric]]  patients.
 
<!--Non–Guideline-Supported Use (pediatric )-->
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Vancomycin in [[pediatric]]  patients.
 
<!--Contraindications-->
|contraindications=* Vancomycin are [[contraindicated]] in patients with known [[hypersensitivity]] to vancomycin.
|warnings======Oral Use Only=====
 
* This preparation for the treatment of [[colitis]] is for oral use only and is not systemically absorbed. Vancomycin CAPSULES must be given orally for treatment of [[staphylococcal]] [[enterocolitis]]  and [[Clostridium difficile]]-associated [[diarrhea]]. Orally administered Vancomycin CAPSULES are not effective for other types of [[infection]]s.
 
* [[Parenteral]] administration of vancomycin is not effective for treatment of [[staphylococcal]] [[enterocolitis]]  and [[C. difficile|C. difficile-associated diarrhea]]. If [[parenteral]] vancomycin therapy is desired, use an [[intravenous]] preparation of vancomycin and consult the package insert accompanying that preparation.
 
=====Potential for Systemic Absorption=====
 
* Clinically significant [[serum]] concentrations have been reported in some patients who have taken multiple oral doses of Vancomycin for active [[C. difficile|C. difficile-associated diarrhea]]. Some patients with [[inflammatory]] disorders of the [[intestinal mucosa]] also may have significant [[systemic]] absorption of vancomycin. These patients may be at risk for the development of [[adverse reaction]]s associated with higher doses of Vancomycin; therefore, monitoring of [[serum]] concentrations of vancomycin may be appropriate in some instances, e.g., in patients with [[renal insufficiency]] and/or [[colitis]] or in those receiving concomitant therapy with an [[aminoglycoside antibiotic]].
 
=====Nephrotoxicity=====
 
* [[Nephrotoxicity]] (e.g., reports of [[renal failure]], [[renal impairment]], blood [[creatinine]] increased) has occurred following oral Vancomycin therapy in [[randomized]] controlled [[clinical studies]], and can occur either during or after completion of therapy. The [[risk]] of [[Nephrotoxicity]] is increased in patients >65 years of age.
 
* In patients >65 years of age, including those with normal [[renal function]] prior to treatment, [[renal function]] should be monitored during and following treatment with Vancomycin to detect potential vancomycin induced [[Nephrotoxicity]].
 
=====Ototoxicity=====
 
* [[Ototoxicity]] has occurred in patients receiving vancomycin. It may be transient or permanent. It has been reported mostly in patients who have been given excessive [[intravenous]] doses, who have an underlying [[hearing loss]], or who are receiving concomitant therapy with another [[ototoxic]] agent, such as an [[aminoglycoside]]. Serial tests of [[auditory]] function may be helpful in order to minimize the risk of [[ototoxicity]].
 
=====Superinfection=====
 
* Use of Vancomycin may result in the overgrowth of nonsusceptible [[bacteria]]. If [[superinfection]] occurs during therapy, appropriate measures should be taken.
 
=====Development of Drug-Resistant bacteria=====
 
* Prescribing Vancomycin in the absence of a proven or strongly suspected [[bacterial infection]] is unlikely to provide benefit to the patient and increases the risk of the development of [[drug resistant]] [[bacteria]].
|clinicalTrials=
* Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the [[clinical studies]] of a drug cannot be directly compared to rates in the [[clinical studies]] of another drug and may not reflect the rates observed in practice.
 
* The data described below reflect exposure to Vancomycin in 260 adult subjects in two Phase 3 [[clinical trial]]s for the treatment of [[diarrhea]] associated with [[C. difficile]]. In both trials, subjects received Vancomycin 125 mg orally four times daily. The mean duration of treatment was 9.4 days. The median age of patients was 67, ranging between 19 and 96 years of age. Patients were predominantly Caucasian (93%) and 52% were male.
 
* [[Adverse reactions]] occurring in ≥ 5% of Vancomycin-treated subjects are shown in TABLE 1. The most common adverse reactions associated with Vancomycin (≥ 10%) were [[nausea]], [[abdominal pain]], and [[hypokalemia]].
 
[[File:Vancomycin adverse reaction table01.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
 
* [[Nephrotoxicity]] (e.g., reports of [[renal failure]], [[renal impairment]], [[blood]] [[creatinine]] increased) occurred in 5% of subjects treated with Vancomycin. [[Nephrotoxicity]] following Vancomycin typically first occurred within one week after completion of treatment (median day of onset was Day 16). [[Nephrotoxicity]] following Vancomycin occurred in 6% of subjects >65 years of age and 3% of subjects ≤65 years of age.
 
* The incidences of [[hypokalemia]], [[urinary tract infection]], [[peripheral edema]], [[insomnia]], [[constipation]], [[anemia]], [[depression]], [[vomiting]], and [[hypotension]] were higher among subjects >65 years of age than in subjects ≤65 years of age.
 
* Discontinuation of study drug due to adverse events occurred in 7% of subjects treated with Vancomycin. The most common adverse events leading to discontinuation of Vancomycin were [[C. difficile]] [[colitis]] (<1%), [[nausea]] (<1%), and [[vomiting]] (<1%).
|postmarketing=* The following adverse reactions have been identified during post-approval use of Vancomycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
 
* [[Ototoxicity]]:
 
:* Cases of hearing loss associated with [[intravenously]] administered vancomycin have been reported. Most of these patients had [[kidney]] dysfunction or a preexisting hearing loss or were receiving concomitant treatment with an [[ototoxic]] drug, [[Ototoxicity]]. [[Vertigo]], [[dizziness]], and [[tinnitus]] have been reported.
 
* Hematopoietic:
 
:* Reversible [[neutropenia]], usually starting 1 week or more after onset of [[intravenous]] therapy with vancomycin or after a total dose of more than 25 g, has been reported for several dozen patients. [[Neutropenia]] appears to be promptly reversible when vancomycin is discontinued. [[Thrombocytopenia]] has been reported.
 
* Miscellaneous:
 
:* Patients have been reported to have had [[anaphylaxis]], [[drug fever]], [[chill]]s, [[nausea]], [[eosinophilia]], [[rashes]] (including [[exfoliative dermatitis]]), [[Stevens-Johnson syndrome]], [[toxic epidermal necrolysis]], and rare cases of [[vasculitis]] in association with the administration of vancomycin.
 
:* A condition has been reported that is similar to the IV-induced syndrome with symptoms consistent with [[anaphylactoid reaction]]s, including [[hypotension]], [[wheezing]], [[dyspnea]], [[urticaria]], [[pruritus]], [[flushing]] of the upper body (“[[Red Man Syndrome]]”), [[pain]] and [[muscle spasm]] of the [[chest]] and back. These reactions usually resolve within 20 minutes but may persist for several hours.
|drugInteractions=There is limited information regarding <i>drug interactions</i> of vancomycin capsule in the drug label.
|FDAPregCat=C
|useInPregnancyFDA=* The highest doses of vancomycin tested were not [[teratogenic]] in rats given up to 200 mg/kg/day IV (1180 mg/m2 or 1 times the recommended maximum human dose based on body surface area) or in rabbits given up to 120 mg/kg/day IV (1320 mg/m2 or 1.1 times the recommended maximum human dose based body surface area). No effects on [[fetal]] weight or development were seen in rats at the highest dose tested or in rabbits given 80 mg/kg/day (880 mg/m2 or 0.74 times the recommended maximum human dose based on body surface area).
 
* In a controlled [[clinical study]], the potential [[ototoxic]] and [[nephrotoxic]] effects of vancomycin on [[infants]] were evaluated when the drug was administered [[intravenously]] to [[pregnant]] women for serious [[staphylococcal]] [[infection]]s complicating [[intravenous]] [[drug abuse]]. Vancomycin was found in [[cord]] [[blood]]. No [[sensorineural hearing loss]] or [[Nephrotoxicity]] attributable to vancomycin was noted. One infant whose mother received vancomycin in the third trimester experienced conductive [[hearing loss]] that was not attributed to the administration of vancomycin. Because the number of subjects treated in this study was limited and vancomycin was administered only in the [[trimesters|second and third trimesters]], it is not known whether vancomycin causes [[fetal]] harm. Because animal [[reproduction]] studies are not always predictive of human response, Vancomycin should be given to a [[pregnant]] woman only if clearly needed.
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Vancomycin in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of Vancomycin during labor and delivery.
|useInNursing=* Vancomycin is excreted in human milk based on information obtained with the [[intravenous]] administration of vancomycin. However, systemic absorption of vancomycin is very low following oral administration of Vancomycin. It is not known whether vancomycin is excreted in human milk, as no studies of vancomycin concentration in human milk after oral administration have been done. Caution should be exercised when Vancomycin is administered to a nursing woman. Because of the potential for adverse events, a decision should be made whether to discontinue [[nursing]] or discontinue the drug, taking into account the importance of the drug to the mother.
|useInPed=There is no FDA guidance on the use of Vancomycin with respect to [[pediatric]]  patients.
|useInGeri=* In [[clinical trials]], 54% of Vancomycin-treated subjects were >65 years of age. Of these, 40% were between the ages of >65 and 75, and 60% were >75 years of age.
 
* [[Clinical studies]] with Vancomycin in [[diarrhea]] associated with [[Clostridium difficile]] have demonstrated that [[geriatric]] subjects are at increased risk of developing [[Nephrotoxicity]]  following treatment with oral Vancomycin, which may occur during or after completion of therapy. In patients >65 years of age, including those with normal [[renal function]] prior to treatment, [[renal function]] should be monitored during and following treatment with Vancomycin to detect potential vancomycin induced [[Nephrotoxicity]].
 
* Patients >65 years of age may take longer to respond to therapy compared to patients ≤65 years of age. Clinicians should be aware of the importance of appropriate duration of Vancomycin treatment in patients >65 years of age and not discontinue or switch to alternative treatment prematurely.
|useInGender=There is no FDA guidance on the use of Vancomycin with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of Vancomycin with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of Vancomycin in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of Vancomycin in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of Vancomycin in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of Vancomycin in patients who are immunocompromised.


The compound was initially labelled '''compound 05865''', but was eventually given the generic name, '''vancomycin''' (derived from the word "vanquished").  One advantage that was quickly apparent was that staphylococci did not develop significant resistance despite serial passage in culture media containing vancomycin.  The rapid development of [[penicillin]]-resistance by staphylococci led to the compound being fast-tracked for approval by the [[Food and Drug Administration|FDA]] in [[1958]].  Eli Lilly first marketed vancomycin hydrochloride under the trade name '''Vancocin'''.<ref name="Moellering2006"/>
<!--Administration and Monitoring-->
|administration=* [[Oral]]


Vancomycin never became first line treatment for ''Staphylococcus aureus'' for several reasons:
* [[Intravenous]]
#The drug must be given [[intravenous]]ly, because it is not absorbed orally.
|monitoring=====Potential for Systemic Absorption=====
#β-lactamase-resistant semi-synthetic penicillins such as [[methicillin]] (and its successors, [[nafcillin]] and [[cloxacillin]]) were subsequently developed.
#Early trials using early impure forms of vancomycin ("Mississippi mud") which were found to be toxic to the ears and to the kidneys;<ref name="Griffiths1981">{{cite journal | author=Griffith RS. | title=Introduction to vancomycin | journal=Rev Infect Dis | year=1981 | volume=3 | pages=S2004 }}</ref> these findings led to vancomycin being relegated to the position of a drug of last resort.


In 2004, [[Eli Lilly and Company|Eli Lilly]] licensed ''Vancocin'' to [[ViroPharma]] in the U.S., [[Flynn Pharma]] in the UK and [[Aspen Pharmacare]] in Australia.  The [[patent]] expired in the early [[1980s]] and generic versions of the drug are also available under various trade names.
* Clinically significant [[serum]] concentrations have been reported in some patients who have taken multiple oral doses of Vancomycin for active [[C. difficile|C. difficile-associated diarrhea]]. Some patients with [[inflammatory]] disorders of the [[intestinal mucosa]] also may have significant systemic absorption of vancomycin. These patients may be at risk for the development of [[adverse reactions]] associated with higher doses of Vancomycin; therefore, monitoring of [[serum]] concentrations of vancomycin may be appropriate in some instances, e.g., in patients with [[renal insufficiency]] and/or [[colitis]] or in those receiving concomitant therapy with an [[aminoglycoside antibiotic]].


==Pharmacology and chemistry==
=====[[Nephrotoxicity]]=====
It is a branched [[Wiktionary:tricyclic|tricyclic]] [[Glycosylation|glycosylated]] [[nonribosomal peptide]] produced by the [[fermentation (biochemistry)|fermentation]] of the [[Actinobacteria]] species ''[[Amycolatopsis|Amycolatopsis orientalis]]'' (formerly designated ''Nocardia orientalis'').


Vancomycin acts by inhibiting proper [[cell wall]] synthesis in Gram-positive bacteria. The mechanism inhibited, and various factors related to entering the outer membrane of [[Gram-negative]] organisms mean that vancomycin is not active against Gram-negative bacteria (except some non-gonococcal species of [[Neisseria]]).
* [[Nephrotoxicity]] (e.g., reports of [[renal failure]], [[renal impairment]], blood [[creatinine]] increased) has occurred following oral Vancomycin therapy in [[randomized]] controlled [[clinical studies]], and can occur either during or after completion of therapy. The risk of [[Nephrotoxicity]] is increased in patients >65 years of age.


Specifically, vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits into the [[peptidoglycan]] matrix; which forms the major structural component of Gram-positive cell walls.
* In patients >65 years of age, including those with normal [[renal function]] prior to treatment, [[renal function]] should be monitored during and following treatment with Vancomycin to detect potential vancomycin induced [[Nephrotoxicity]].
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of Vancomycin in the drug label.


The large [[hydrophilic]] molecule is able to form [[hydrogen bond]] interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Normally this is a five-point interaction. This binding of vancomycin to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix.
<!--Overdosage-->
|overdose=* 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.


Vancomycin exhibits [[atropisomer]]ism — it has two chemically distinct [[rotamer]]s owing to the rotational restriction of the chlorotyrosine residue (on the right hand side of the figure). The form present in the drug is the thermodynamically more stable [[conformer]], and, importantly, has more potent activity.
* To obtain up-to-date information about the treatment of [[overdose]], a good resource is your certified Regional [[Poison]] Control Center. Telephone numbers of certified [[poison]] control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug [[overdoses]], interaction among drugs, and unusual drug kinetics.
|drugBox={{drugbox2
| verifiedrevid = 470628926
| IUPAC_name = (1''S'',2''R'',18''R'',19''R'',22''S'',25''R'',28''R'',40''S'')- 48- {[(2''S'',3''R'',4''S'',5''S'',6''R'')- 3- {[(2''S'',4''S'',5''S'',6''S'')- 4- amino- 5- hydroxy- 4,6- dimethyloxan- 2- yl]oxy}- 4,5- dihydroxy- 6- (hydroxymethyl)oxan- 2- yl]oxy}- 22- (carbamoylmethyl)- 5,15- dichloro- 2,18,32,35,37- pentahydroxy- 19- [(2''R'')- 4- methyl- 2- (methylamino)pentanamido]- 20,23,26,42,44- pentaoxo- 7,13- dioxa- 21,24,27,41,43- pentaazaoctacyclo[26.14.2.2<sup>3,6</sup>.2<sup>14,17</sup>.1<sup>8,12</sup>.1<sup>29,33</sup>.0<sup>10,25</sup>.0<sup>34,39</sup>]pentaconta- 3,5,8(48),9,11,14,16,29(45),30,32,34,36,38,46,49- pentadecaene- 40- carboxylic acid
| image = Vancomycin.png
| width = 300
| image2 = Vancomycin ball-and-stick.png
| width2 = 300


Vancomycin can be given orally, but this method is very expensive.  It may also be used in treatment for [[clostridium difficile]].
<!--Clinical data-->
| tradename = Vancocin
| Drugs.com = {{drugs.com|monograph|vancocin}}
| MedlinePlus = a604038
| pregnancy_AU = B2
| pregnancy_category = B (PO) / C (IV)<small>([[United States|US]])</small>
| legal_AU = S4
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = POM
| legal_US = Rx-only
| legal_status =
| routes_of_administration = [[intravenous|IV]], oral
| licence_US = Vancocin


==Clinical use==
<!--Pharmacokinetic data-->
===Indications===
| bioavailability = Negligible (oral)
Vancomycin is indicated for the treatment of serious, life-threatening infections by [[Gram-positive]] bacteria which are unresponsive to other less toxic antibiotics.  In particular, vancomycin should not be used to treat methicillin-sensitive [[Staphylococcus aureus]] because it is inferior to penicillins such as [[nafcillin]].<ref>{{cite journal|author=Small PM, Chambers HF|title=Vancomycin for ''Staphylococcus aureus'' endocarditis in intravenous drug users|journal=Antimicrob Agents Chemother|year=1990|volume=34|pages=1227&ndash;31|pmid=2393284}}</ref><ref>{{cite journal|author=Gonzalez C, Rubio M, Romero-Vivas J, Gonzalez M, Picazo JJ|title=Bacteremic pneumonia due to ''Staphylococcus aureus'': a comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms|journal=Clin Infect Dis|year=1999|volume=29|pages=1171&ndash;7|pmid=10524959|doi=10.1086/313440}}</ref>
| metabolism = Excreted unchanged
| elimination_half-life = 4–11 hours <small>(adults)</small><br />6-10 days <small>(adults, impaired renal function)</small>
| excretion = Renal


The increasing emergence of vancomycin-resistant [[enterococcus|enterococci]] has resulted in the development of guidelines for use by the [[Centers for Disease Control]] (CDC) Hospital Infection Control Practices Advisory Committee. These guidelines restrict use of vancomycin to the following indications:<ref name="AMH2006">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3</ref>
<!--Identifiers-->
*treatment of serious infections caused by susceptible organisms resistant to [[penicillin]]s ([[methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] and multi-resistant ''[[Staphylococcus epidermidis]]'' (MRSE)) or in individuals with serious allergy to [[penicillin]]s
| CAS_number_Ref = {{cascite|correct|??}}
*[[pseudomembranous colitis]] (relapse or unresponsive to [[metronidazole]] treatment)
| CAS_number = 1404-90-6
*For treatment of infections caused by gram-positive microorganisms in patients who have serious allergies to beta-lactam antimicrobials. (http://wonder.cdc.gov/wonder/prevguid/m0039349/m0039349.asp)
| ATC_prefix = A07
*antibacterial prophylaxis for [[endocarditis]] following certain procedures in penicillin-[[hypersensitivity|hypersensitive]] individuals at high risk
| ATC_suffix = AA09
*surgical prophylaxis for major procedures involving implantation of [[prosthesis|prostheses]] in institutions with a high rate of MRSA or MRSE
| ATC_supplemental = {{ATC|J01|XA01}}
| PubChem = 14969
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00512
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 14253
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6Q205EH1VU
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00212
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 28001
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 262777


===Adverse effects===
<!--Chemical data-->
Common [[adverse drug reaction]]s (≥1% of patients) associated with IV vancomycin include: local pain, which may be severe and/or [[thrombophlebitis]].
| C=66 | H=75 | Cl=2 | N=9 | O=24
| molecular_weight = 1449.3 g.mol<sup>-1</sup>
| smiles = C[C@H]1[C@H]([C@@](C[C@@H](O1)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2Oc3c4cc5cc3Oc6ccc(cc6Cl)[C@H]([C@H](C(=O)N[C@H](C(=O)N[C@H]5C(=O)N[C@@H]7c8ccc(c(c8)-c9c(cc(cc9O)O)[C@H](NC(=O)[C@H]([C@@H](c1ccc(c(c1)Cl)O4)O)NC7=O)C(=O)O)O)CC(=O)N)NC(=O)[C@@H](CC(C)C)NC)O)CO)O)O)(C)N)O
| InChI = 1/C66H75Cl2N9O24/c1-23(2)12-34(71-5)58(88)76-49-51(83)26-7-10-38(32(67)14-26)97-40-16-28-17-41(55(40)101-65-56(54(86)53(85)42(22-78)99-65)100-44-21-66(4,70)57(87)24(3)96-44)98-39-11-8-27(15-33(39)68)52(84)50-63(93)75-48(64(94)95)31-18-29(79)19-37(81)45(31)30-13-25(6-9-36(30)80)46(60(90)77-50)74-61(91)47(28)73-59(89)35(20-43(69)82)72-62(49)92/h6-11,13-19,23-24,34-35,42,44,46-54,56-57,65,71,78-81,83-87H,12,20-22,70H2,1-5H3,(H2,69,82)(H,72,92)(H,73,89)(H,74,91)(H,75,93)(H,76,88)(H,77,90)(H,94,95)/t24-,34+,35-,42+,44-,46+,47+,48-,49+,50-,51+,52+,53+,54-,56+,57+,65-,66-/m0/s1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C66H75Cl2N9O24/c1-23(2)12-34(71-5)58(88)76-49-51(83)26-7-10-38(32(67)14-26)97-40-16-28-17-41(55(40)101-65-56(54(86)53(85)42(22-78)99-65)100-44-21-66(4,70)57(87)24(3)96-44)98-39-11-8-27(15-33(39)68)52(84)50-63(93)75-48(64(94)95)31-18-29(79)19-37(81)45(31)30-13-25(6-9-36(30)80)46(60(90)77-50)74-61(91)47(28)73-59(89)35(20-43(69)82)72-62(49)92/h6-11,13-19,23-24,34-35,42,44,46-54,56-57,65,71,78-81,83-87H,12,20-22,70H2,1-5H3,(H2,69,82)(H,72,92)(H,73,89)(H,74,91)(H,75,93)(H,76,88)(H,77,90)(H,94,95)/t24-,34+,35-,42+,44-,46+,47+,48-,49+,50-,51+,52+,53+,54-,56+,57+,65-,66-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MYPYJXKWCTUITO-LYRMYLQWSA-N
}}
|mechAction=* The bactericidal action of vancomycin against [[Staphylococcus aureus]] and the vegetative cells of [[Clostridium difficile]] results primarily from inhibition of [[cell wall]] [[biosynthesis]]. In addition, vancomycin alters [[bacteria]] l [[cell membrane]] [[permeability]] and [[RNA synthesis]].
|structure=* Vancomycin for oral administration contain chromatographically purified vancomycin hydrochloride, a [[glycopeptide|tricyclic glycopeptide]] [[antibiotic]] derived from [[Amycolatopsis orientalis]] (formerly Nocardia orientalis), which has the [[chemical formula]] C66H75Cl2N9O24•HCl. The [[molecular weight]] of vancomycin hydrochloride is 1485.73; 500 mg of the base is equivalent to 0.34 mmol.


Damage to the kidneys and to the hearing were a side effect of the early impure versions of vancomycin, and these were prominent in the clinical trials conducted in the mid-1950s.  Later trials using purer forms of vancomycin found that [[nephrotoxicity]] is an infrequent adverse effect (0.1–1% of patients), but that this is accentuated in the presence of [[aminoglycoside]]s.<ref>{{cite journal | author=Farber BF, Moellering RC Jr. | title=Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. | journal=Antimicrob Agents Chemother | year=1983 | volume=23 | pages=138 }}</ref>
* Vancomycin hydrochloride has the structural formula:


Rare adverse effects (<0.1% of patients) include: [[anaphylaxis]], [[toxic epidermal necrolysis]], [[erythema multiforme]], red man syndrome (''[[Vancomycin#Red man syndrome|see below]]''), [[superinfection]], [[thrombocytopenia]], [[neutropenia]], [[leukopenia|leucopenia]], [[tinnitus]], dizziness and/or ototoxicity (''[[Vancomycin#Ototoxicity|see below]]'').<ref name="AMH2006" />
[[File:Vancomycin structural formula.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]


Lately it has been emphasized that vancomycin can induce platelet-reactive antibodies in the patient, leading to severe [[thrombocytopenia]] and bleeding with florid [[petechial hemorrhages]], [[ecchymoses]], and [[wet purpura]]. <ref>{{cite journal | author=Drygalski A, Curtis BR | title=Vancomycin-Induced Immune Thrombocytopenia | journal= N Engl J Med | year=2007 | volume=356 | pages=904  | doi=10.1056/NEJMoa065066}}</ref>
<!--Pharmacodynamics-->
|PD=There is limited information regarding <i>Pharmacodynamics</i> of Vancomycin in the drug label.


===Dosing considerations===
<!--Pharmacokinetics-->
====Intravenous vs oral administration====
|PK=* Vancomycin is poorly absorbed after oral administration. During multiple dosing of 250 mg every 8 hours for 7 doses, [[fecal]] concentrations of vancomycin in volunteers exceeded 100 mg/kg in the majority of samples. No [[blood]] concentrations were detected and [[urinary]] recovery did not exceed 0.76%. In anephric subjects with no [[inflammatory bowel disease]] who received vancomycin oral solution 2 g for 16 days, [[blood]] concentrations of vancomycin were less than or equal to 0.66 μg/mL in 2 of 5 subjects. No measurable blood concentrations were attained in the other 3 subjects. Following doses of 2 g daily, concentrations of drug were >3100 mg/kg in the [[feces]] and <1 μg/mL in the [[serum]] of subjects with normal [[renal function]] who had [[C. difficile|C. difficile-associated diarrhea]]. After multiple-dose oral administration of vancomycin, measurable [[serum]] concentrations may occur in patients with active [[C. difficile|C. difficile-associated diarrhea]], and, in the presence of [[renal impairment]], the possibility of accumulation exists. It should be noted that the total systemic and [[renal]] clearances of vancomycin are reduced in the elderly.
Vancomycin needs to be given [[intravenous]]ly (IV) for systemic therapy since it does not cross through the intestinal lining. It is a large hydrophilic molecule which partitions poorly across the gastrointestinal [[mucosa]]. The only indication for oral vancomycin therapy is in the treatment of [[pseudomembranous colitis]], where it must be given orally to reach the site of infection in the colon. Inhaled vancomycin has also been used ([[off-label]]), via [[nebulizer]], for treatment of various infections of the upper and lower respiratory tract.
|nonClinToxic=====Carcinogenesis, Mutagenesis, Impairment of Fertility=====


====Red man syndrome====<!-- This section is linked from [[Vancomycin]] -->
* No long-term [[carcinogenesis]] studies in animals have been conducted.
* [[Vancomycin]] must be administered in a dilute solution slowly, over at least 60 minutes (maximum rate of 10 mg/minute for doses >500 mg).<ref name="AMH2006" />
* This is due to the high incidence of [[pain]] and [[thrombophlebitis]] and to avoid an infusion reaction known as the '''red man syndrome''' or '''red neck syndrome'''.
* This syndrome, usually appearing within 4–10 minutes after the commencement or soon after the completion of an infusion, is characterised by flushing and/or and an [[erythematous]] rash that affects the face, neck and upper torso.
*  Less frequently, [[hypotension]] and [[angioedema]] may also occur.
* Symptoms may be treated with [[antihistamine]]s, including [[diphenhydramine]].<ref name="Sivagnanam2003">Sivagnanam S, Deleu D. Red man syndrome. Crit Care 2003;7(2):119–120. PMID 12720556. ([http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=12720556 full text])</ref>
===Vancomycin target troughs===
* While treating a patient with vancomycin a target trough of at least 10 mcg/mL should be achieved. This is important due to the following:
* Decreases the risk of microbes with elevated vancomycin minimum inhibitory concentrations (MICs).
* Microbes with elevated MICs towards vancomycin have shown decreased susceptibility to other antimicrobials agents such as [[daptomycin]]. Thus, maintaining a trough of atleast 10 mcg/mL helps in avoiding development of resistance to other microbes too.


===Therapeutic drug monitoring===
* At concentrations up to 1000 μg/mL, vancomycin had no [[mutagenic]] effect in vitro in the mouse [[lymphoma]] forward [[mutation]] assay or the primary rat [[hepatocyte]] unscheduled [[DNA synthesis]] assay. The concentrations tested in vitro were above the peak [[plasma]] vancomycin concentrations of 20 to 40 μg/mL usually achieved in humans after slow [[infusion]] of the maximum recommended dose of 1 g. Vancomycin had no [[mutagenic]] effect in vivo in the Chinese hamster sister [[chromatid]] exchange [[assay]] (400 mg/kg IP) or the mouse [[micronucleus]] assay (800 mg/kg IP).
Vancomycin activity is considered to be time-dependent – that is, antimicrobial activity depends on the duration that the drug level exceeds the [[minimum inhibitory concentration]] (MIC) of the target organism. Thus, peak levels have not been shown to correlate with efficacy or toxicity – indeed concentration monitoring is unnecessary in most cases. Circumstances where [[therapeutic drug monitoring]] (TDM) is warranted include: patients receiving concomitant aminoglycoside therapy, patients with (potentially) altered [[pharmacokinetics|pharmacokinetic]] parameters, patients on [[hemodialysis|haemodialysis]], during high dose or prolonged treatment, and patients with impaired renal function. In such cases, trough concentrations are measured.<ref name="AMH2006" /><ref name="Cantu1994">Cantu TG, Yamanaka-Yuen NA, Lietman PS. Serum vancomycin concentrations: reappraisal of their clinical value. Clin Infect Dis 1994;19(6):1180-2. PMID 8038306</ref><ref name="Moellering1994">Moellering RC Jr. Monitoring serum vancomycin levels: climbing the mountain because it is there? Clin Infect Dis 1994;18(4):544-6. PMID 8038307</ref><ref name="Karam1999"> Karam CM, McKinnon PS, Neuhauser MM, Rybak MJ. Outcome assessment of minimizing vancomycin monitoring and dosing adjustments. Pharmacotherapy 1999;19(3):257-66. PMID 10221365</ref>


==Toxicity==
* No definitive fertility studies have been conducted.
Vancomycin has traditionally been considered a [[nephrotoxic]] and [[ototoxic]] drug, based on observations by early investigators of elevated serum levels in renally impaired patients who had experienced ototoxicity, and subsequently through case reports in the medical literature. However, as the use of vancomycin increased with the spread of [[MRSA]] beginning in the seventies, it was recognised that the previously reported rates of toxicity were not being observed. This was attributed to the removal of the impurities present in the earlier formulation of the drug, although those impurities were not specifically tested for toxicity.<ref name="Levine2006"/>
|clinicalStudies=====[[Diarrhea]] Associated with [[Clostridium difficile]]=====


===Nephrotoxicity===
* In two [[trials]], Vancomycin 125 mg orally four times daily for 10 days was evaluated in 266 adult subjects with [[C. difficile|C. difficile-associated diarrhea]] ([[CDAD]]). Enrolled subjects were 18 years of age or older and received no more than 48 hours of treatment with oral Vancomycin or oral/[[intravenous]] [[metronidazole]] in the 5 days preceding enrollment. [[CDAD]] was defined as ≥3 loose or watery [[bowel]] movements within the 24 hours preceding enrollment, and the presence of either [[C. difficile]] toxin A or B, or [[pseudomembranes]] on [[endoscopy]] within the 72 hours preceding enrollment. Subjects with [[fulminant]] [[C. difficile]] disease, sepsis with [[hypotension]], [[ileus]], [[peritoneal]] signs or severe [[hepatic disease]] were excluded.
Subsequent reviews of accumulated case reports of vancomycin-related [[nephrotoxicity]] found that many of the patients had also received other known nephrotoxins, particularly [[aminoglycosides]]. Most of the rest had other confounding factors, or insufficient data regarding the possibility of such, that prohibited the clear association of vancomycin with the observed renal dysfunction.  


In 1994, Cantu and colleagues found that the use of vancomycin monotherapy was clearly documented in only three of 82 available cases in the literature.<ref name="Cantu1994" /> Prospective and retrospective studies attempting to evaluate the incidence of vancomycin-related nephrotoxicity have largely been methodologically flawed and have produced variable results. The most methodologically sound investigations indicate that the actual incidence of vancomycin-induced nephrotoxicity is around 5–7%. To put this into context, similar rates of renal dysfunction have been reported for [[cefamandole]] and [[benzylpenicillin]], two reputedly non-nephrotoxic antibiotics.  
* [[Efficacy]] analyses were performed on the Full Analysis Set (FAS), which included [[randomized]] subjects who received at least one dose of Vancomycin and had any post-dosing investigator evaluation data (N=259; 134 in Trial 1 and 125 in Trial 2).


Additionally, evidence to relate nephrotoxicity to vancomycin serum levels is inconsistent. Some studies have indicated an increased rate of nephrotoxicity when trough levels exceed 10 µg/mL, but others have not reproduced these results. Nephrotoxicity has also been observed with concentrations within the "therapeutic" range as well. Essentially, the reputation of vancomycin as a nephrotoxin is over-stated, and it has not been demonstrated that maintaining vancomycin serum levels within certain ranges will prevent its nephrotoxic effects, when they do occur.
* The demographic profile and baseline [[CDAD]] characteristics of enrolled subjects were similar in the two trials. Vancomycin-treated subjects had a median age of 67 years, were mainly white (93%), and male (52%). [[CDAD]] was classified as severe (defined as 10 or more unformed bowel movements per day or [[WBC]] ≥15000/mm3) in 25% of subjects, and 47% were previously treated for [[CDAD]].


===Ototoxicity===<!-- This section is linked from [[Vancomycin]] -->
* [[Efficacy]] was assessed by using clinical success, defined as diarrhea resolution and the absence of severe abdominal discomfort due to [[CDAD]], on Day 10. An additional [[efficacy]] endpoint was the time to resolution of [[diarrhea]], defined as the beginning of [[diarrhea]] resolution that was sustained through the end of the prescribed active treatment period.
Attempts to establish rates of vancomycin-induced ototoxicity are even more difficult due to the scarcity of quality evidence. The current consensus is that clearly related cases of vancomycin ototoxicity are rare. The association between vancomycin serum levels and ototoxicity is also uncertain. While cases of ototoxicity have been reported in patients whose vancomycin serum level exceeded 80 µg/mL, cases have been reported in patients with therapeutic levels as well. Thus, it also remains unproven that [[therapeutic drug monitoring]] of vancomycin for the purpose of maintaining "therapeutic" levels will prevent ototoxicity.


===Interactions with other nephrotoxins===
* The results for clinical success for Vancomycin-treated subjects in both [[trials]] are shown in TABLE 2.
Another area of controversy and uncertainty concerns the question of whether, and if so, to what extent, vancomycin increases the toxicity of other nephrotoxins. Clinical studies have yielded variable results, but animal models indicate that there probably is some increased nephrotoxic effect when vancomycin is added to nephrotoxins such as aminoglycosides. However, a dose- or serum level-effect relationship has not been established.


==Antibiotic resistance==
[[File:Vancomycin clinical studies Table 02.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
===Intrinsic resistance===
There are a few [[gram-positive]] bacteria that are intrinsically resistant to vancomycin: these are [[Leuconostoc]] and [[Pediococcus]] species, but these organisms are rare causes of disease in humans.<ref name="Swenson1990">{{cite journal | author=Swenson JM, Facklam RR, Thornsberry C | title=Antimicrobial susceptibility of vancomycin-resistant ''Leuconostoc, Pediococcus'' and ''Lactobacillus'' species | journal=Antimicrob Agents Chemother | year=1990 | volume=34 | pages=543&ndash;49 }}</ref>  Most [[Lactobacillus]] species are also intrinsically resistant to vancomycin<ref name="Swenson1990"/> (the exception is the finding of a few strains (but not all) of ''[[Lactobacillus acidophilus|L. acidophilus]]''<ref>{{cite journal | author=Hamilton-Miller JM, Shah S | year=1998 | title=Vancomycin susceptibility as an aid to the identification of lactobacilli | journal=Lett Appl Microbiol | year=1998 | volume=26 | pages=153&ndash;54  | doi=10.1046/j.1472-765X.1998.00297.x}}</ref>).


Most [[gram-negative]] bacteria are intrinsically resistant to vancomycin because of their outer membrane is impermeable to large glycopeptide molecules<ref>{{cite book | author=Quintiliani R Jr, Courvalin P | chapter=Mechanisms of Resistance to Antimicrobial Agents | title=Manual of Clinical Microbiology | editor=Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH | publisher=ASM Press | location=Washington DC | year=1995 | edition=6th | pages=1319 | isbn=1-55581-086-1 }}</ref> (with the exception of some non-gonococcal [[Neisseria]] species).<ref>{{cite journal | author=Geraci JE, Wilson WR | title=Vancomycin therapy for infective enocarditis | journal=Rev Infect Dis | year=1981 | volume=3(Suppl) | pages=S250&ndash;58 }}</ref>
* The median time to resolution of diarrhea was 5 days and 4 days in Trial 1 and Trial 2, respectively. For subjects older than 65 years of age, the median time to resolution was 6 days and 4 days in Trial 1 and Trial 2, respectively. In subjects with [[diarrhea]] resolution at end-of-treatment with [[Vancomycin]], recurrence of [[CDAD]] during the following four weeks occurred in 25 of 107 (23%) and 18 of 102 (18%) in Trial 1 and Trial 2, respectively.


===Acquired resistance===
* Restriction [[Endonuclease]] Analysis (REA) was used to identify [[C. difficile]] baseline isolates in the BI group. In Trial 1, the Vancomycin-treated subjects were classified at baseline as follows 31 (23%) with BI strain, 69 (52%) with non-BI strain, and 34 (25%) with unknown [[strain]]. Clinical success rates were 87% for BI strain, 81% for non-BI [[strain]], and 76% for unknown [[strain]].  In subjects with diarrhea resolution at end-of-treatment with Vancomycin, recurrence of [[CDAD]] during the following four weeks occurred in 7 of 26 subjects with BI strain, 12 of 56 subjects with non-BI strain, and 6 of 25 subjects with unknown strain.
Acquired microbial [[antibiotic resistance|resistance]] to vancomycin is a growing problem, particularly within health care facilities such as hospitals. With vancomycin being the last-line antibiotic for serious [[Gram-positive]] infections there is the growing prospect that resistance will result in a return to the days when fatal bacterial infections were common.  
|howSupplied=* Vancomycin CAPSULES are available in:


[[Vancomycin-resistant enterococcus]] (VRE) emerged in [[1987]]. Vancomycin resistance emerged in more common pathogenic organisms during the [[1990s]] and [[2000s]], including [[vancomycin-resistant Staphylococcus aureus|vancomycin-intermediate ''Staphylococcus aureus'']] (VISA), [[vancomycin-resistant Staphylococcus aureus|vancomycin-resistant ''Staphylococcus aureus'']] (VRSA), and vancomycin-resistant ''[[Clostridium difficile]]''.<ref name="Smith1999">Smith TL, Pearson ML, Wilcox KR, Cruz C, Lancaster MV, Robinson-Dunn B, et al. Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus Working Group. [[New England Journal of Medicine|N Engl J Med]] 1999;340(7):493-501. PMID 10021469</ref><ref name="McDonald2005">McDonald LC, Killgore GE, Thompson A, et al. Emergence of an epidemic, toxin gene variant strain of Clostridium difficile responsible for outbreaks in the United States between 2000 and 2004. N Engl J Med 2005;353:2433-2441. PMID 16322603</ref> There is some suspicion that agricultural use of [[avoparcin]], another similar glycopeptide antibiotic, has contributed to the emergence of vancomycin-resistant organisms.
:* The 125 mg* capsules have an opaque blue cap and opaque brown body imprinted with “3125” on the cap and “Vancomycin HCL 125 MG” on the body in white ink. A carton contains 2 blister packs. Each blister pack contains 10 capsules for a total of 20 capsules per carton. NDC No. 62559-310-20.


One mechanism of resistance to vancomycin appears to be alteration to the terminal [[amino acid]] residues of the NAM/NAG-peptide subunits, normally D-alanyl-D-alanine, which vancomycin binds to. Variations such as D-alanyl-D-lactate and D-alanyl-D-serine result in only a 4-point hydrogen bonding interaction being possible between vancomycin and the peptide. This loss of just one point of interaction results in a 1000-fold decrease in affinity.
:* The 250 mg* capsules have an opaque blue cap and opaque lavender body imprinted with “3126” on the cap and “Vancomycin HCL 250 MG” on the body in white ink. A carton contains 2 blister packs. Each blister pack contains 10 capsules for a total of 20 capsules per carton. NDC No. 62559-311-20.
|storage=* Store at controlled room temperature, 59° to 86°F (15° to 30°C).
|fdaPatientInfo=* Patients should be counseled that [[antibacterial]] drugs including Vancomycin should only be used to treat [[bacterial]] [[infections]]. They do not treat viral infections (e.g., the common cold). When Vancomycin is prescribed to treat a [[bacterial infection]], patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that [[bacteria]]  will develop resistance and will not be treatable by Vancomycin or other [[antibacterial]] drugs in the future.


In ''Enterococci'' this modification appears to be due to the expression of an enzyme which alters the terminal residue. Three main resistance variants have been characterised to date among resistant ''Enterococcus faecium'' and ''E. faecalis'' populations.
* VANCOCIN® is a registered U.S. trademark owned by ANI Pharmaceuticals, Inc.
*VanA - resistance to vancomycin and [[teicoplanin]], inducible on exposure to these agents
*VanB - lower level resistance, inducible by vancomycin but strains may remain susceptible to teicoplanin
*VanC - least clinically important, resistance only to vancomycin, constitutive resistance


The development and use of novel antibiotics such as [[linezolid]] and [[daptomycin]] is expected to delay, but not halt, the emergence of bacteria resistant to all available antibiotics.
:* Rx Only


==References==
:* Distributed by:
{{reflist|2}}


== See also ==
:* ANI Pharmaceuticals, Inc.
* [[Drug resistance]]
* [[Antibiotic resistance]]
* [[Methicillin-resistant Staphylococcus aureus]]
* [[Vancomycin-resistant Staphylococcus aureus]]
* [[Vancomycin-resistant enterococcus]]


==External links==
:* Baudette, MN 56623
* [http://www.vancomycin.co.uk Vancomycin information site and forum]
|alcohol=* Alcohol-Vancomycin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}
{{Other antibacterials}}


[[Category:Glycopeptide antibiotics]]
<!--Brand Names-->
|brandNames=* Vancocin HCl Pulvules®
* Vancocin HCl®
* Vancoled®
|lookAlike=* IV VANC®  - INVANZ®
|drugShortage=
}}
{{PillImage
|fileName=No image.jpg
}}
{{LabelImage
|fileName=Vancomycin package label01.png
}}
{{LabelImage
|fileName=Vancomycin package label02.png
}}
<!--Pill Image-->


<!--Label Display Image-->


[[ar:فانكومايسن]]
<!--Category-->
[[de:Vancomycin]]
[[es:Vancomicina]]
[[fr:Vancomycine]]
[[hr:Vankomicin]]
[[nl:Vancomycine]]
[[ja:バンコマイシン]]
[[no:Vancomycin]]
[[pl:Wankomycyna]]
[[pt:Vancomicina]]
[[ru:Ванкомицин]]
[[fi:Vankomysiini]]
[[tr:Vankomisin]]
[[zh:萬古黴素]]
[[sv:Vankomycin]]


{{jb1}}
[[Category:Drug]]
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Latest revision as of 17:23, 20 August 2015

Vancomycin (oral)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adeel Jamil, M.D. [2]

Disclaimer

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Overview

Vancomycin (oral) is a glycopeptide, antibiotics that is FDA approved for the treatment of C. difficile-associated diarrhea, enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains). Common adverse reactions include nausea, vomiting, abdominal pain, diarrhea, and hypokalemia.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • Orally administered Vancomycin is not effective for other types of infections.
  • To reduce the development of drug-resistant bacteria and maintain the effectiveness of Vancomycin CAPSULES and other antibacterial drugs, Vancomycin CAPSULES should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosing Information

Off-Label Use and Dosage (Adult)

Non–Guideline-Supported Use

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

  • The usual daily dosage is 40 mg/kg in 3 or 4 divided doses for 7 to 10 days. The total daily dosage should not exceed 2 g.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Vancomycin in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Vancomycin in pediatric patients.

Contraindications

Warnings

Oral Use Only
Potential for Systemic Absorption
Nephrotoxicity
  • In patients >65 years of age, including those with normal renal function prior to treatment, renal function should be monitored during and following treatment with Vancomycin to detect potential vancomycin induced Nephrotoxicity.
Ototoxicity
  • Ototoxicity has occurred in patients receiving vancomycin. It may be transient or permanent. It has been reported mostly in patients who have been given excessive intravenous doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside. Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity.
Superinfection
  • Use of Vancomycin may result in the overgrowth of nonsusceptible bacteria. If superinfection occurs during therapy, appropriate measures should be taken.
Development of Drug-Resistant bacteria
  • Prescribing Vancomycin in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug resistant bacteria.

Adverse Reactions

Clinical Trials Experience

  • Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
  • The data described below reflect exposure to Vancomycin in 260 adult subjects in two Phase 3 clinical trials for the treatment of diarrhea associated with C. difficile. In both trials, subjects received Vancomycin 125 mg orally four times daily. The mean duration of treatment was 9.4 days. The median age of patients was 67, ranging between 19 and 96 years of age. Patients were predominantly Caucasian (93%) and 52% were male.
This image is provided by the National Library of Medicine.
  • Discontinuation of study drug due to adverse events occurred in 7% of subjects treated with Vancomycin. The most common adverse events leading to discontinuation of Vancomycin were C. difficile colitis (<1%), nausea (<1%), and vomiting (<1%).

Postmarketing Experience

  • The following adverse reactions have been identified during post-approval use of Vancomycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
  • Hematopoietic:
  • Reversible neutropenia, usually starting 1 week or more after onset of intravenous therapy with vancomycin or after a total dose of more than 25 g, has been reported for several dozen patients. Neutropenia appears to be promptly reversible when vancomycin is discontinued. Thrombocytopenia has been reported.
  • Miscellaneous:

Drug Interactions

There is limited information regarding drug interactions of vancomycin capsule in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • The highest doses of vancomycin tested were not teratogenic in rats given up to 200 mg/kg/day IV (1180 mg/m2 or 1 times the recommended maximum human dose based on body surface area) or in rabbits given up to 120 mg/kg/day IV (1320 mg/m2 or 1.1 times the recommended maximum human dose based body surface area). No effects on fetal weight or development were seen in rats at the highest dose tested or in rabbits given 80 mg/kg/day (880 mg/m2 or 0.74 times the recommended maximum human dose based on body surface area).


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Vancomycin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Vancomycin during labor and delivery.

Nursing Mothers

  • Vancomycin is excreted in human milk based on information obtained with the intravenous administration of vancomycin. However, systemic absorption of vancomycin is very low following oral administration of Vancomycin. It is not known whether vancomycin is excreted in human milk, as no studies of vancomycin concentration in human milk after oral administration have been done. Caution should be exercised when Vancomycin is administered to a nursing woman. Because of the potential for adverse events, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

There is no FDA guidance on the use of Vancomycin with respect to pediatric patients.

Geriatic Use

  • In clinical trials, 54% of Vancomycin-treated subjects were >65 years of age. Of these, 40% were between the ages of >65 and 75, and 60% were >75 years of age.
  • Patients >65 years of age may take longer to respond to therapy compared to patients ≤65 years of age. Clinicians should be aware of the importance of appropriate duration of Vancomycin treatment in patients >65 years of age and not discontinue or switch to alternative treatment prematurely.

Gender

There is no FDA guidance on the use of Vancomycin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Vancomycin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Vancomycin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Vancomycin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Vancomycin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Vancomycin in patients who are immunocompromised.

Administration and Monitoring

Administration

Monitoring

Potential for Systemic Absorption=

Nephrotoxicity
  • In patients >65 years of age, including those with normal renal function prior to treatment, renal function should be monitored during and following treatment with Vancomycin to detect potential vancomycin induced Nephrotoxicity.

IV Compatibility

There is limited information regarding IV Compatibility of Vancomycin in the drug label.

Overdosage

  • To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics.

Pharmacology

Template:Px
Template:Px
Vancomycin (oral)
Systematic (IUPAC) name
(1S,2R,18R,19R,22S,25R,28R,40S)- 48- {[(2S,3R,4S,5S,6R)- 3- {[(2S,4S,5S,6S)- 4- amino- 5- hydroxy- 4,6- dimethyloxan- 2- yl]oxy}- 4,5- dihydroxy- 6- (hydroxymethyl)oxan- 2- yl]oxy}- 22- (carbamoylmethyl)- 5,15- dichloro- 2,18,32,35,37- pentahydroxy- 19- [(2R)- 4- methyl- 2- (methylamino)pentanamido]- 20,23,26,42,44- pentaoxo- 7,13- dioxa- 21,24,27,41,43- pentaazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta- 3,5,8(48),9,11,14,16,29(45),30,32,34,36,38,46,49- pentadecaene- 40- carboxylic acid
Identifiers
CAS number 1404-90-6
ATC code A07AA09 J01XA01 (WHO)
PubChem 14969
DrugBank DB00512
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 1449.3 g.mol-1
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability Negligible (oral)
Metabolism Excreted unchanged
Half life 4–11 hours (adults)
6-10 days (adults, impaired renal function)
Excretion Renal
Therapeutic considerations
Licence data

US

Pregnancy cat.

B2(AU) B (PO) / C (IV)(US)

Legal status

Prescription Only (S4)(AU) POM(UK) [[Prescription drug|Template:Unicode-only]](US)

Routes IV, oral

Mechanism of Action

Structure

  • Vancomycin hydrochloride has the structural formula:
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Vancomycin in the drug label.

Pharmacokinetics

  • Vancomycin is poorly absorbed after oral administration. During multiple dosing of 250 mg every 8 hours for 7 doses, fecal concentrations of vancomycin in volunteers exceeded 100 mg/kg in the majority of samples. No blood concentrations were detected and urinary recovery did not exceed 0.76%. In anephric subjects with no inflammatory bowel disease who received vancomycin oral solution 2 g for 16 days, blood concentrations of vancomycin were less than or equal to 0.66 μg/mL in 2 of 5 subjects. No measurable blood concentrations were attained in the other 3 subjects. Following doses of 2 g daily, concentrations of drug were >3100 mg/kg in the feces and <1 μg/mL in the serum of subjects with normal renal function who had C. difficile-associated diarrhea. After multiple-dose oral administration of vancomycin, measurable serum concentrations may occur in patients with active C. difficile-associated diarrhea, and, in the presence of renal impairment, the possibility of accumulation exists. It should be noted that the total systemic and renal clearances of vancomycin are reduced in the elderly.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility=

  • At concentrations up to 1000 μg/mL, vancomycin had no mutagenic effect in vitro in the mouse lymphoma forward mutation assay or the primary rat hepatocyte unscheduled DNA synthesis assay. The concentrations tested in vitro were above the peak plasma vancomycin concentrations of 20 to 40 μg/mL usually achieved in humans after slow infusion of the maximum recommended dose of 1 g. Vancomycin had no mutagenic effect in vivo in the Chinese hamster sister chromatid exchange assay (400 mg/kg IP) or the mouse micronucleus assay (800 mg/kg IP).
  • No definitive fertility studies have been conducted.

Clinical Studies

Diarrhea Associated with Clostridium difficile=

  • Efficacy analyses were performed on the Full Analysis Set (FAS), which included randomized subjects who received at least one dose of Vancomycin and had any post-dosing investigator evaluation data (N=259; 134 in Trial 1 and 125 in Trial 2).
  • The demographic profile and baseline CDAD characteristics of enrolled subjects were similar in the two trials. Vancomycin-treated subjects had a median age of 67 years, were mainly white (93%), and male (52%). CDAD was classified as severe (defined as 10 or more unformed bowel movements per day or WBC ≥15000/mm3) in 25% of subjects, and 47% were previously treated for CDAD.
  • Efficacy was assessed by using clinical success, defined as diarrhea resolution and the absence of severe abdominal discomfort due to CDAD, on Day 10. An additional efficacy endpoint was the time to resolution of diarrhea, defined as the beginning of diarrhea resolution that was sustained through the end of the prescribed active treatment period.
  • The results for clinical success for Vancomycin-treated subjects in both trials are shown in TABLE 2.
This image is provided by the National Library of Medicine.
  • The median time to resolution of diarrhea was 5 days and 4 days in Trial 1 and Trial 2, respectively. For subjects older than 65 years of age, the median time to resolution was 6 days and 4 days in Trial 1 and Trial 2, respectively. In subjects with diarrhea resolution at end-of-treatment with Vancomycin, recurrence of CDAD during the following four weeks occurred in 25 of 107 (23%) and 18 of 102 (18%) in Trial 1 and Trial 2, respectively.
  • Restriction Endonuclease Analysis (REA) was used to identify C. difficile baseline isolates in the BI group. In Trial 1, the Vancomycin-treated subjects were classified at baseline as follows 31 (23%) with BI strain, 69 (52%) with non-BI strain, and 34 (25%) with unknown strain. Clinical success rates were 87% for BI strain, 81% for non-BI strain, and 76% for unknown strain. In subjects with diarrhea resolution at end-of-treatment with Vancomycin, recurrence of CDAD during the following four weeks occurred in 7 of 26 subjects with BI strain, 12 of 56 subjects with non-BI strain, and 6 of 25 subjects with unknown strain.

How Supplied

  • Vancomycin CAPSULES are available in:
  • The 125 mg* capsules have an opaque blue cap and opaque brown body imprinted with “3125” on the cap and “Vancomycin HCL 125 MG” on the body in white ink. A carton contains 2 blister packs. Each blister pack contains 10 capsules for a total of 20 capsules per carton. NDC No. 62559-310-20.
  • The 250 mg* capsules have an opaque blue cap and opaque lavender body imprinted with “3126” on the cap and “Vancomycin HCL 250 MG” on the body in white ink. A carton contains 2 blister packs. Each blister pack contains 10 capsules for a total of 20 capsules per carton. NDC No. 62559-311-20.

Storage

  • Store at controlled room temperature, 59° to 86°F (15° to 30°C).

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

  • Patients should be counseled that antibacterial drugs including Vancomycin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Vancomycin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Vancomycin or other antibacterial drugs in the future.
  • VANCOCIN® is a registered U.S. trademark owned by ANI Pharmaceuticals, Inc.
  • Rx Only
  • Distributed by:
  • ANI Pharmaceuticals, Inc.
  • Baudette, MN 56623

Precautions with Alcohol

  • Alcohol-Vancomycin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • Vancocin HCl Pulvules®
  • Vancocin HCl®
  • Vancoled®

Look-Alike Drug Names

  • IV VANC® - INVANZ®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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