vancomycin (Rx)

10% (Oral)

1-10% (Oral)

Frequency Not Defined (IV)

Immune system disorders: Hypersensitivity reactions (eg, anaphylaxis, “red man syndrome”)

Skin and subcutaneous tissue disorders: Erythema and pruritus which are manifestations of rashes including exfoliative dermatitis, linear IgA bullous dermatosis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Renal and urinary disorders: Acute kidney injury and interstitial nephritis

Ear and labyrinth disorders: Tinnitus, hearing loss, vertigo

Blood and lymphatic system disorders: Agranulocytosis, neutropenia, pancytopenia, leukopenia, thrombocytopenia, eosinophilia

Gastrointestinal disorders: Pseudomembranous colitis Cardiac disorders: Cardiac arrest, chest pain

General disorders and administration site conditions: General discomfort, fever, chills, phlebitis, injection site irritation, injection site pain and necrosis following intramuscular injection, chemical peritonitis following intraperitoneal administration (Vancomycin not approved for IM and intraperitoneal administration)

Laboratory abnormalities: Elevated blood urea nitrogen, elevated serum creatinine

Musculoskeletal and connective tissue disorders: Muscle pain

Nervous system disorders: Dizziness

Respiratory, thoracic and mediastinal disorders: Wheezing, dyspnea

Vascular disorders: Hypotension, shock, vasculitis

Postmarketing Reports (All Formulations)

Ototoxicity: Hearing loss associated IV administration (most cases had coexisting renal impairment or pre-existing hearing loss, or were coadministered an ototoxic drug), vertigo, dizziness, and tinnitus

Hematopoietic: Reversible neutropenia, thrombocytopenia

Miscellaneous: Anaphylaxis, drug fever, chills, nausea, eosinophilia, rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, and vasculitis

Contraindications

Hypersensitivity

Cautions

Rapid IV administration may result in flushing, pruritus, hypotension, erythema, and urticaria

Systemic vancomycin exposure may result in acute kidney injury (AKI) and interstitial nephritis; risk of AKI increases as systemic exposure increases; additional risk factors for AKI include concomitant use of nephrotoxic drugs, patients with pre-existing renal impairment, or with comorbidities that predispose to renal impairment

Endocarditis prophylaxis: Use only for high-risk patients, per AHA guidelines

Ototoxicity may occur; toxicity proportional to amount of drug given and duration of treatment; presence of tinnitus or vertigo may indicate vestibular injury; discontinue if signs of ototoxicity occur

Risk of neutropenia increases with doses >25 g (reversible following discontinuation of therapy)

Avoid extravasation; necrosis may occur

Prolonged use may result in fungal or bacterial superinfection

Use caution in patients with renal impairment; monitor trough concentrations if multiple oral doses administered

Hemorrhagic occlusive retinal vasculitis, including permanent loss of vision, occurred in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery; safety and efficacy of vancomycin administered by intracameral or intravitreal route not established by adequate and well- controlled trials; vancomycin not indicated for prophylaxis of endophthalmitis

Oral vancomycin only indicated for treatment of pseudomembranous colitis due to C. difficile and enterocolitis due to S. aureus; not effective for systemic infections

Clinically significant serum concentrations reported in some patients who have taken multiple oral doses of vancomycin for active C. difficile-associated diarrhea

Prescribe vancomycin only for a proven or strongly suspected bacterial infection to prevent the development of drug resistant bacteria

Hypotension, including shock and cardiac arrest, wheezing, dyspnea, urticaria, muscular and chest pain may occur with rapid IV administration; reactions may be more severe in younger patients, particularly children, and in patients receiving concomitant muscle relaxant anesthetics

Inflammation at the site of injection reported; vancomycin is irritating to tissue and must be given by a secure IV route to reduce the risk of local irritation and phlebitis

Pregnancy

Animal reproduction studies have not been conducted with vancomycin

Unknown whether vancomycin can affect reproduction capacity

In a controlled clinical study, potential ototoxic and nephrotoxic effects of vancomycin on infants were evaluated when administered to pregnant women for serious staphylococcal infections complicating IV drug abuse

Lactation

Vancomycin is excreted in human milk

Exercise caution 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 to discontinue the drug, taking into account the importance of the drug to the mother

Mechanism of Action

Inhibits cell-wall biosynthesis; blocks glycopeptide polymerization by binding tightly to D-alanyl-D-alanine portion of cell wall precursor

Absorption

Distribution

Distributed widely in body tissues and fluid, except for cerebrospinal fluid (CSF)

Relative diffusion from blood into CSF: Good only with inflammation (exceeds usual minimal inhibitory concentrations); CSF level nil with normal meninges, 20-30% of blood level with inflamed meninges

Protein bound: ~50%

Vd: 0.3-0.43 L/kg (IV)

Metabolism

There is no apparent metabolism of the vancomycin

Elimination

Half-life (IV): 4-6 hr (normal renal function); 7.5 days (anephric patients)

Mean clearance (flexible bag): 0.058 L/kg/hr (plasma); 0.048 L/kg/hr (renal)

Excretion: Urine (IV; 80-90% as unchanged drug); primarily feces (PO)

IV Compatibilities

Solution: D5W/0.9% NaCl, D5W, D10W, LR, sodium bicarbonate 3.75%, 0.9% NaCl, D5W and LR, Normosol and D5W, 0.9% NaCl, Isolyte

Additive: Amikacin, atracurium, calcium gluconate, cefepime, cimetidine, corticotropin, dimenhydrinate, erythromycin, famotidine, hydrocortisone, meropenem, ofloxacin, potassium chloride, ranitidine, verapamil, vitamins B and C

Syringe: Caffeine

Y-site (partial list): Acyclovir, alatrofloxacin, aldesleukin, allopurinol, amifostine, amiodarone, ampicillin, ampicillin-sulbactam, cefpirome, ceftizoxime, clarithromycin, diltiazem, esmolol, fluconazole, insulin, labetalol, lorazepam, linezolid, magnesium sulfate, midazolam, morphine, nicardipine, ondansetron, paclitaxel, pancuronium, perphenazine, remifentanil, sargramostim, sodium bicarbonate, tacrolimus, teniposide

IV Incompatibilities

Vancomycin solution has a low pH and may cause chemical or physical instability when it is mixed with other compounds

Mixtures of solutions of vancomycin and beta-lactam antibacterial drugs have been shown to be physically incompatible

Likelihood of precipitation increases with higher concentrations of vancomycin; adequately flush IV lines between administering these antibacterial drugs

IV Preparation

Add 10 mL of SWI to 500-mg vial and 20 mL of SWI to 1-g vial to yield 50 mg/mL solution; further dilution is required, depending on method of administration

Intermittent infusion: Dilute 500 mg with ≥100 mL of diluent and 1 g with ≥200 mL of diluent (NS or D5W)

Continuous infusion: Dilute in sufficient amount to permit infusion over 24 hours

Oral Preparation (Firvanq)

Tap bottom edges of bottle to loosen powder

Shake grape-flavored diluent for a few seconds

Open diluent and transfer about half the required volume of diluent into the vancomycin powder bottle

Shake powder bottle vertically for ~45 seconds

Add remaining grape-flavored diluent into powder bottle; shake bottle for ~30 seconds

Instruct patient to shake reconstituted solution well before each use and to use an oral dosing device that measures the appropriate volume of the oral solution in milliliters

Oral Administration

Take with food

IV Administration

Intermittent (preferred): Administer over 60 minutes; not to exceed 10 mg/min

Continuous: Administer over 24 hours

Storage

Capsules: Store at 15-30°C (59-86°F)