vancomycin (Rx)

>10%

Bitter taste (PO)

Erythematous rash on face and upper body (IV; red neck or red man syndrome; related to infusion rate)

Hypotension accompanied by flushing (IV)

Nausea and vomiting (PO)

1-10%

Chills (IV)

Drug fever (IV)

Eosinophilia (IV)

Rash (IV)

Fatique (PO)

Peripheral edema (PO)

Urinary tract infection (PO)

Back pain (PO)

Headache (PO)

Reversible neutropenia (IV)

Phlebitis (IV)

<1%

Nephrotoxicity

Ototoxicity (especially with large doses)

Stevens-Johnson syndrome

Thrombocytopenia

Vasculitis

Postmarketing Reports

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); the risk of AKI increases as systemic exposure/serum levels increase; additional risk factors for AKI in patients vancomycin include receipt of concomitant drugs known to be nephrotoxic, in patients with pre-existing renal impairment or with co-morbidities that predispose to renal impairment; interstitial nephritis also reported in patients receiving vancomycin

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

Unclear whether drug is nephrotoxic or neurotoxic in regular doses, but increased nephrotoxicity and ototoxicity are associated with pre-existing renal impairment, advanced age, dehydration; also appears to potentiate nephro-/neurotoxic effects of other drugs

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

Pregnancy

Animal reproduction studies have not been conducted with vancomycin

Unknown whether vancomycin can affect reproduction capacity

In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin on infants were evaluated when the drug was 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

PO, poor; IM, erratic; intraperitoneal, ~38%

Peak serum time (IV): Immediately after completion of infusion

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%

Elimination

Half-life: 5-11 hr (adults); 6-10 hr (newborns); 2-2.3 hr (children); 4 hr (infants and children 3 months to 4 years); 200-250 hr (renal impairment or end-stage renal disease)

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

Additive: Aminophylline(?), amobarbital, aztreonam (may be compatible at low concentrations of vancomycin and aztreonam), chlorothiazide, chloramphenicol, dexamethasone, dexamethasone sodium phosphate, heparin(?), pentobarbital, phenobarbital, sodium bicarbonate(?)

Syringe: Heparin

Y-site: Heparin, albumin, amphotericin B cholesteryl sulfate, aztreonam(?), bivalirudin, cefazolin(?), cefotaxime(?), cefotetan(?), cefoxitin(?), ceftazidime(?), ceftriaxone(?), cefuroxime(?), foscarnet, gatifloxacin, idarubicin, methotrexate(?), nafcillin, omeprazole, piperacillin(?), piperacillin-tazobactam (?), propofol(?), sargramostim, ticarcillin (may be compatible at low concentrations of vancomycin), ticarcillin-clavulanate (may be compatible at low concentrations of vancomycin), warfarin (may be compatible at low concentrations of warfarin)

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)

Drug must be reconstituted by the healthcare provider (eg, a pharmacist) to produce the oral solution

Hold bottle and tap bottom edges on a hard surface to loosen powder

Slowly peel back inner foil seal liner from bottle

Shake grape-flavored diluent for a few seconds

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

Replace cap and shake vancomycin powder bottle vertically for ~45 seconds

Add the remaining grape-flavored diluent into the vancomycin powder bottle Shake the 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

Refrigerate reconstituted solutions at 2-8°C (36-46°F); discard reconstituted solution after 14 days, or if it appears hazy or contains particulates

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)