vancomycin (Rx)

10% (Oral)

capsule

• Nausea (17%)
• Abdominal pain (15%)
• Hypokalemia (13%)

1-10% (Oral)

capsule

• Vomiting (9%)
• Diarrhea (9%)
• Pyrexia (9%)
• Flatulence (8%)
• Urinary tract infection (8%)
• Headache (7%)
• Peripheral edema (6%)
• Back pain (6%)
• Fatigue (5%)
• Nephrotoxicity (5%)

Frequency Not Defined (IV)

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

Skin and subcutaneous tissue disorders: Severe dermatologic reactions such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear lgA bullous dermatosis (LABD)

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

Single-dose flexible bags only

• Skin and subcutaneous tissue disorders: Drug rash with eosinophilia and systemic symptoms (DRESS)

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

Severe dermatologic reactions such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear lgA bullous dermatosis (LABD) reported in association with vancomycin; cutaneous signs or symptoms reported include skin rashes, mucosal lesions, and blisters; discontinue therapy at first appearance of signs and symptoms of TEN, SJS, DRESS, AGEP, or LABD

Drug interactions overview

• Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing and anaphylactoid reactions
• Monitor renal function in patients receiving vancomycin and concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, (eg, amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, or cisplatin)

Pregnancy

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

Single-dose flexible bags only

• Some formulations of Vancomycin Injection are not recommended for use during the first or second trimester of pregnancy because it contains the excipients, PEG 400 and NADA, which caused fetal malformations in animal reproduction studies; advise pregnant women of the potential risk to the fetus; if therapy with vancomycin injection is needed during first or second trimester of pregnancy, use other available formulations of vancomycin, free of PEG 400 and NADA

• Perform a pregnancy test in females of reproductive potential prior to prescribing this formulation

• Animal data

  • Reproduction studies in rabbits with intravenous doses of PEG 400 at approximately 8 times the maximum daily human dose based on systemic exposures of PEG 400 during organogenesis resulted in fetal spinal malformations
  • Reproduction studies in rabbits and rats using intravenous doses of NADA at approximately 32 and 20 times the maximum daily human dose, respectively, based on systemic exposures of NADA resulted in maternal toxicity and fetal spinal and cardiovascular malformations in rabbits, and maternal toxicity with no adverse embryo-fetal effects in rats

Capsule

• Systemic absorption of vancomycin is low following oral administration of capsule; however, absorption may vary depending on various factors; there are no available data on vancomycin use in pregnant women to assess risk of major birth defects or miscarriage; available published data on intravenous vancomycin use in pregnancy during second and third trimesters have not shown an association with adverse maternal or fetal outcomes

Lactation

Intravenous

• 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

Vancocin

• There are no data on presence of vancomycin in human milk, effects on breastfed infant, or on milk production following oral administration; systemic absorption of vancomycin is low following oral administration of VANCOCIN; therefore, it is unlikely to result in clinically relevant exposure in breastfeeding infants; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

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

Absorption

Oral

• Poorly absorbed
• After 250-mg capsules PO q8hr for 7 doses, fecal concentrations of vancomycin in volunteers exceeded 100 mcg/g in majority of samples

IV

• Peak serum time: 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%

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

Single-dose flexible bags

• Do NOT use in series connections
• Such use could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete

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

Vancomycin concentration and volume after reconstitution

• Reconstituted vancomycin concentration: 25 mg/mL

  • 3.75 g: Dilute with 147 mL of grape-flavored diluent; final reconstituted volume: 150 mL
  • 7.5 g: Dilute with 295 mL of grape-flavored diluent; final reconstituted volume: 300 mL

• Reconstituted vancomycin concentration: 50 mg/mL

  • 7.5 g: Dilute with 145 mL of grape-flavored diluent; final reconstituted volume: 150 mL
  • 10.5 g: Dilute with 203 mL of grape-flavored diluent; final reconstituted volume: 210 mL
  • 15 g: Dilute with 289 mL of grape-flavored diluent; final reconstituted volume: 300 mL

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)

Vials

• Store at room temperature, 15-30°C (59-86°F)
• Reconstituted solutions stable at 2-8°C for at least 4 days

Single-dose bags

• Store below 25°C

Powder for oral solution

• Unopened kits: Refrigerate, 2-8°C (36-46°F); do not freeze; keep container tightly closed
• Protect from light
• Reconstituted solutions: Refrigerate at 2-8°C (36-46°F); discard reconstituted solution after 14 days