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Vancomycin (Oral-Local)


VA CLASSIFICATION
Primary: AM900

Commonly used brand name(s): Vancocin.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antibacterial (oral-local)—

Indications

Accepted

Colitis, antibiotic-associated (treatment)
Colitis, pseudomembranous (treatment) or
Diarrhea, antibiotic-associated (treatment)—Oral-local vancomycin is indicated in the treatment of antibiotic-associated diarrhea or colitis caused by Clostridium difficile . It is also indicated in the treatment of pseudomembranous colitis caused by C. difficile . {09} {10} {11} {12} {16}
—Oral metronidazole is considered the drug of choice by many clinicians because it has been found to be as effective as vancomycin in the treatment of patients with mild to moderate C. difficile colitis {03} {04}, and it is much more cost-effective. {03} {04} Also, the emergence of multidrug-resistant strains of enterococci, including vancomycin-resistant strains, is of concern. {04} {05} {06}

Enterocolitis, staphylococcal (treatment)—Oral-local vancomycin is indicated in the treatment of staphylococcal enterocolitis. {09} {10}

—Not all species or strains of a particular organism may be susceptible to vancomycin.

Unaccepted
Oral vancomycin is not effective in the treatment of other intestinal infections or in systemic infections. {09}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Vancomycin hydrochloride: 1485.74 {01}

Mechanism of action/Effect:

Oral vancomycin inhibits bacterial cell wall synthesis {10} by binding tightly to the D-alanyl- D-alanine portion of cell wall precursors; this leads to destruction of the bacterial cell by lysis; vancomycin may also alter permeability of bacterial cytoplasmic membranes and may selectively inhibit ribonucleic acid (RNA) synthesis. {10}

Absorption:

Poorly absorbed from gastrointestinal tract. {10}

Peak serum concentration:

<1 mcg per mL; may be somewhat higher in patients with inflammatory disorders of the colonic mucosa or renal function impairment. {10}

Fecal concentration

Approximately 350 mcg per gram following oral doses of 125 mg four times a day. {09}

Approximately 3100 mcg per gram following oral doses of 2 grams daily. {09} {10}

Elimination:
    Primarily fecal. {10}


Precautions to Consider

Carcinogenicity

No long-term carcinogenicity studies have been performed in animals. {10}

Mutagenicity

No mutagenic potential was found in standard laboratory tests. {10}

Pregnancy/Reproduction
Fertility—
No definitive fertility studies have been performed. {10}

Pregnancy—
Intravenous vancomycin crosses the placenta. In one small controlled study, infants of mothers treated with vancomycin in their second or third trimester of pregnancy had no sensorineural hearing loss or nephrotoxicity that was attributed to vancomycin. {10} {14}

Teratology studies revealed no evidence of harm to the fetuses of rats given the normal human dose and rabbits given 1.1 times the human dose on a mg per square meter of body surface area basis. {10}

FDA Pregnancy Category B {10}.

Breast-feeding

Orally administered vancomycin is poorly absorbed from the gastrointestinal tracts of the mother and infant, so the small amount of this medication that may be distributed into breast milk will result in only low blood levels in the nursing infant {10}.

Pediatrics

Appropriate studies on the relationship of age to the effects of oral vancomycin have not been performed in the pediatric population. Safety and efficacy have not been established {10}. However, no pediatrics-specific problems have been documented to date.


Geriatrics


Appropriate studies on the relationship of age to the effects of oral vancomycin have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Cholestyramine or
» Colestipol{11}{15}    (cholestyramine and colestipol anion-exchange resins have been shown to bind oral vancomycin significantly when used concurrently, resulting in decreased stool concentrations and marked reduction in antibacterial activity; concurrent use is not recommended; patients should be advised to take oral vancomycin and these medications several hours apart)


Nephrotoxic medications, other (see Appendix II ){07}{08}{10}{13}    (concurrent use with oral vancomycin may, on rare occasions, increase the potential for nephrotoxicity; this is most likely to occur in patients also receiving aminoglycosides and in patients with severe colitis, which may increase vancomycin absorption; caution is recommended when these medications are used concurrently with oral vancomycin)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Hypersensitivity to vancomycin
» Inflammatory intestinal disorders, other{10}{13}    (may result in increased absorption and toxicity)


Renal function impairment, severe{10}{13}    (serum concentrations may be significantly elevated in patients with severe colitis, possibly resulting in increased toxicity)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Renal function determinations{10}    (may be required periodically during therapy in patients with renal function impairment)


For Clostridium difficile colitis
Colonoscopy and/or
Proctosigmoidoscopy{24}    (proctosigmoidoscopy may be useful to document the presence of pseudomembranes and/or relapse in selected patients who have persistent symptoms of C. difficile colitis and do not respond to therapy; however, since proctosigmoidoscopy is not always reliable in the diagnosis of C. difficile colitis due to rectal sparing and the presence of colitis in the more distal portions of the colon, colonoscopy may also be required in patients with a negative proctosigmoidoscopy)


» Stool toxin assays{02}{11}    (enzyme immunoassay of stool samples for the presence of C. difficile toxins may be required prior to treatment of patients with antibiotic-associated diarrhea or colitis to document the presence of C. difficile toxins; however, C. difficile and its toxins may persist following treatment with oral vancomycin despite clinical improvement; follow-up cultures and toxin assays are not recommended if clinical improvement is complete)




Side/Adverse Effects

Note: Since vancomycin is poorly absorbed from the gastrointestinal tract and serum concentrations are low, systemic side/adverse effects are unlikely to occur except perhaps during prolonged administration or administration of unusually large oral doses. {10} {17} For systemic side/adverse effects of vancomycin, see Vancomycin (Systemic).

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare {19} {28}
    
Skin rash, including exfoliative dermatitis (scaling of skin), macular rash (redness or discoloration of skin), urticaria (hives), or vasculitis (welting of skin)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent {10} {18}
    
Bitter or unpleasant taste
    
mouth irritation —with oral solution
    
nausea or vomiting





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
Vancomycin overdose may cause acute renal failure and oliguria {27}.

Treatment of overdose
To decrease absorption—Gastric emptying within the first 2 hours of overdose may decrease absorption {27}; multiple doses of activated charcoal may also decrease absorption {27}.

To enhance elimination—Poorly removed by dialysis; hemofiltration and hemoperfusion with polysulfone resin have been used to increase clearance {10}.

Supportive care—Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Vancomycin (Oral).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to vancomycin
Other medications, especially cholestyramine and colestipol
Other medical problems, especially other inflammatory intestinal disorders

Proper use of this medication

Proper administration technique
For oral liquids—Using a calibrated liquid-measuring device; not using after expiration date
» Compliance with full course of therapy

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Importance of physician checking progress during and after treatment

Checking with physician if no improvement within a few days

» Avoiding concurrent use of vancomycin and cholestyramine or colestipol; if concurrent use is necessary, taking vancomycin and these medications several hours apart

» Checking with physician or pharmacist before taking any other kind of diarrhea medication


Side/adverse effects
Signs of potential side effects, especially skin rash


General Dosing Information
For Clostridium difficile colitis—

   • Oral vancomycin is indicated in the treatment of C. difficile colitis, which may be caused by various antibiotics (e.g., cephalosporins, lincomycins, penicillins). C. difficile colitis may result in severe watery diarrhea, which may occur during therapy or up to several weeks after therapy is discontinued {12}. If diarrhea occurs, administration of antiperistaltic antidiarrheals (e.g., atropine and diphenoxylate combination, loperamide, opiates) is not recommended since they may delay the removal of toxins from the colon, thereby prolonging and/or worsening the condition {11} {16}.
   • Mild cases of C. difficile colitis may respond to discontinuation of the medication alone. Moderate to severe cases may require fluid, electrolyte, and protein replacement. {11} {16}
   • In cases not responding to the above measures or in more severe cases, oral doses of vancomycin, metronidazole, or cholestyramine may be used. Oral vancomycin is usually effective at a dose of 125 mg every six hours for seven to ten days. The dose of metronidazole is 250 to 500 mg every eight hours and the dose of cholestyramine is 4 grams four times a day. Recurrences, which occur in approximately 25% of patients treated with vancomycin or metronidazole, may be treated with a second course of vancomycin, oral metronidazole, or oral bacitracin. {02} {09} {10} {11}
   • Cholestyramine resin has been shown to bind C. difficile toxin in vitro . If cholestyramine resin is administered in conjunction with oral vancomycin, the medications should be administered several hours apart since the cholestyramine resin has been shown to bind oral vancomycin also. {11} {12} {15} {16}
   • If a patient is too ill for oral therapy, vancomycin may be administered by enema, by passage of a long intestinal tube, or by direct instillation through a colonostomy or ileostomy {11} {13} {21}. In addition, metronidazole may also be administered intravenously since 6 to 15% of metronidazole and its metabolites are excreted into the feces {25} {26}.


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of vancomycin base, not the hydrochloride salt.


VANCOMYCIN HYDROCHLORIDE CAPSULES USP

Usual adult and adolescent dose
Clostridium difficile colitis or diarrhea or
Staphylococcal enterocolitis
Oral, 125 to 500 mg (base) every six hours for seven to ten days {09} {10}. May be repeated if necessary {12}.

Note: Some studies suggest that this dose results in fecal concentrations of vancomycin that far exceed the minimum inhibitory concentration (MIC) for C. difficile . Also, studies have shown that 125 mg (base) every six hours is as effective as higher doses. {22}



Usual adult prescribing limits
2 grams (base) per day. {10}

Usual pediatric dose
Clostridium difficile colitis or diarrhea or
Staphylococcal enterocolitis
Oral, 10 mg (base) per kg of body weight, up to 125 mg, every six hours for seven to ten days {09} {10}. May be repeated if necessary {12}.

Note: Some medical experts recommend doses of up to 50 mg (base) per kg of body weight per day {23}.



Usual pediatric prescribing limits
2 grams (base) per day {10} {23}.

Strength(s) usually available
U.S.—


125 mg (base) (Rx) [Vancocin]{10}


250 mg (base) (Rx) [Vancocin]{10}

Canada—


125 mg (base) (Rx) [Vancocin]{09}


250 mg (base) (Rx) [Vancocin]{09}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Continue medicine for full time of treatment.


VANCOMYCIN HYDROCHLORIDE FOR ORAL SOLUTION USP

Usual adult and adolescent dose
See Vancomycin Hydrochloride Capsules USP .

Usual adult prescribing limits
See Vancomycin Hydrochloride Capsules USP .

Usual pediatric dose
See Vancomycin Hydrochloride Capsules USP .

Usual pediatric prescribing limits
See Vancomycin Hydrochloride Capsules USP .

Strength(s) usually available
U.S.—


250 mg (base) per 5 mL (when reconstituted according to manufacturer's instructions) (Rx) [Vancocin]{10}


500 mg (base) per 6 mL (when reconstituted according to manufacturer's instructions) (Rx) [Vancocin (ethanol up to 40 mg per gram )]{10}

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Preparation of dosage form:
Add 20 mL of distilled or deionized water to each 1-gram bottle to provide a concentration of 250 mg per 5 mL, or 115 mL of diluent to each 10-gram bottle to provide a concentration of 500 mg per 6 mL. Mix thoroughly to dissolve. {10}

For intravenous dosage form used orally—To prepare initial dilution for oral use, the contents of each 500-mg vial may be diluted in distilled water. The resulting solution may be given to the patient to drink or it may be administered through a nasogastric tube to help prevent or minimize the bitter or unpleasant taste and nausea or vomiting. {20}

Stability:
After reconstitution, solutions retain their potency for 14 days if refrigerated. {10}

Auxiliary labeling:
   • Refrigerate.
   • Continue medicine for full time of treatment.
   • Beyond-use date.

Note: When dispensing, include a calibrated liquid-measuring device.




Revised: 04/15/1998



References
  1. Vancomycin hydrochloride. In: Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 774.
  1. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992; 15: 573-81.
  1. Teasley DG, Gerding DN, Olson MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium difficile -associated diarrhoea and colitis. Lancet 1983; 2: 1043-6.
  1. Caputo GM, Weitekamp MR. The treatment of Clostridium difficile colitis [letter]. JAMA 1993; 269(16): 2088.
  1. Spera RV, Farber BF. Multiply-resistant Enterococcus faecium . The nosocomial pathogen of the 1990s. JAMA 1992; 268(18): 2563-4.
  1. Centers for Disease Control. Nosocomial enterococci resistant to vancomycin—United States, 1989–1993. JAMA 1993; 270(15): 1796.
  1. Cantu TG, Yamanaka-Yuen NA, Lietmen PS. Serum vancomycin concentrations: reappraisal of their clinical value. Clin Infect Dis 1994; 18: 533-43.
  1. Moellering RC. Monitoring serum vancomycin levels: climbing the mountain because it is there [editorial] Clin Infect Dis 1994; 18: 544-6.
  1. Vancomycin (Vancocin, Eli Lilly). In: Gillis MS, editor. CPS Compendium of pharmaceuticals and specialties. 32nd ed. Ontario, Canada: Canadian Pharmaceutical Association; 1997. p. 1682-4.
  1. Vancocin package insert (Lilly—US), Rev 1/93, Rec 5/93; Rev 6/96, Rec 9/97.
  1. Fekety R, Shah AB. Diagnosis and treatment of Clostridium difficile colitis. JAMA 1993; 269(1): 71-5.
  1. Mandell GL, Douglas RG, Bennett JE, editors. Principles and practice of infectious diseases. 3rd ed. New York: Churchill Livingstone; 1990. p. 836-9.
  1. Pasic M, Carrel T, Opravil M, et al. Systemic absorption after local intracolonic vancomycin in pseudomembranous colitis. Lancet 1993; 342: 443.
  1. Reyes MP, Ostrea EM, Cabinian AE, et al. Vancomycin during pregnancy: does it cause hearing loss or nephrotoxicity in the infant? Am J Obstet Gynecol 1989; 161: 977-81.
  1. King CY, Barriere SL. Analysis of the in vitro interaction between vancomycin and cholestyramine. Antimicrob Agents Chemother 1981; 19(2): 326-7.
  1. Gotz VP, Rand KH. Medical management of antimicrobial-associated diarrhea and colitis. Pharmacotherapy 1982; 2: 100-9.
  1. Spitzer PG, Eliopoulos GM. Systemic absorption of enteral vancomycin in a patient with pseudomembranous colitis. Ann Intern Med 1984; 100(4): 533-4.
  1. Kraus DH. Potential compliance problems with vancomycin oral solution. Am J Hosp Pharm 1992; 49: 562.
  1. McCullough JM, Dielman DG, Peery D. Oral vancomycin-induced rash: case report and review of the literature. DICP Ann Pharmacother 1991; 25: 1326-8.
  1. Bryan CS, White WL. Safety of oral vancomycin in functionally anephric patients. Antimicrob Agents Chemother 1978; 14(4): 634-5.
  1. Pasic M, Jost R, Carrell T, et al. Intracolonic vancomycin for pseudomembranous colitis. N Engl J Med 1993; 329(8): 583.
  1. Fekety R, Silva J, Kauffman C, et al. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med 1989; 86: 15-9.
  1. Benitz WE, Tatro DS. The pediatric drug handbook. 2nd ed. Chicago: Year Book Medical Publishers Inc; 1988. p. 571-3.
  1. Reviewers" responses to monograph revision of 5/94.
  1. Panel comment, 7/94.
  1. Gorbach SL, Bartlett JG, Blacklow NR, editors. Infectious diseases. Philadelphia: WB Saunders Co; 1992. p. 262.
  1. Ellenhorn MJ, editor. Ellenhorn's medical toxicology. Maryland: Williams & Wilkins; 1997. p. 236-8.
  1. Panel comment, 2/13/98.
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