INDICATIONS AND USAGE Vancomycin Hydrochloride for Injection, USP is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (β-lactam-resistant) staphylococci.

It is indicated for penicillin-allergic patients, for patients who cannot receive or who have failed to respond to other drugs, including the penicillins or cephalosporins, and for infections caused by vancomycin-susceptible organisms that are resistant to other antimicrobial drugs.

Vancomycin Hydrochloride for Injection, USP is indicated for initial therapy when methicillin-resistant staphylococci are suspected, but after susceptibility data are available, therapy should be adjusted accordingly.

Vancomycin Hydrochloride for Injection, USP is effective in the treatment of staphylococcal endocarditis.

Its effectiveness has been documented in other infections due to staphylococci, including septicemia, bone infections, lower respiratory tract infections, skin and skin structure infections.

When staphylococcal infections are localized and purulent, antibiotics are used as adjuncts to appropriate surgical measures.

Vancomycin Hydrochloride for Injection, USP has been reported to be effective alone or in combination with an aminoglycoside for endocarditis caused by S.

viridans or S.

bovis .

For endocarditis caused by enterococci (e.g., E.

faecalis ), vancomycin has been reported to be effective only in combination with an aminoglycoside.

Vancomycin Hydrochloride for Injection, USP has been reported to be effective for the treatment of diphtheroid endocarditis.

Vancomycin Hydrochloride for Injection, USP has been used successfully in combination with either rifampin, an aminoglycoside, or both in early-onset prosthetic valve endocarditis caused by S.

epidermidis or diphtheroids.

Specimens for bacteriologic cultures should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to vancomycin.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Vancomycin Hydrochloride for Injection, USP and other antibacterial drugs, Vancomycin Hydrochloride for Injection, USP should be used only to treat or prevent 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.

The parenteral form of vancomycin hydrochloride may be administered orally for treatment of antibiotic-associated pseudomembranous colitis produced by C.

difficile and for staphylococcal enterocolitis.

Parenteral administration of vancomycin hydrochloride alone is of unproven benefit for these indications.

Vancomycin is not effective by the oral route for other types of infections.

WARNINGS I n f u s i o n Reactions Rapid bolus administration (e.g., over several minutes) may be associated with exaggerated hypotension, including shock and rarely cardiac arrest.

Vancomycin hydrochloride for injection should be administered in a diluted solution over a period of not less than 60 minutes to avoid rapid-infusion-related reactions.

Stopping the infusion usually results in prompt cessation of these reactions.

Nephrotoxicity Systemic vancomycin exposure may result in acute kidney injury (AKI).

The risk of AKI increases as systemic exposure/serum levels increase.

Monitor renal function in all patients, especially patients with underlying renal impairment, patients with co-morbidities that predispose to renal impairment, and patients receiving concomitant therapy with a drug known to be nephrotoxic.

Ototoxicity Ototoxicity has occurred in patients receiving vancomycin hydrochloride for injection.

It may be transient or permanent.

It has been reported mostly in patients who have been given excessive doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside.

Vancomycin should be used with caution in patients with renal insufficiency because the risk of toxicity is appreciably increased by high, prolonged blood concentrations.

Dosage of vancomycin hydrochloride for injection must be adjusted for patients with renal dysfunction (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ).

Severe Dermatologic Reactions 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 IgA bullous dermatosis (LABD) have been reported in association with the use of vancomycin.

Cutaneous signs or symptoms reported include skin rashes, mucosal lesions, and blisters.

Discontinue Vancomycin hydrochloride for injection at the first appearance of signs and symptoms of TEN, SJS, DRESS, AGEP, or LABD.

Clostridium Difficile Associated Diarrhea (CDAD) Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including vancomycin hydrochloride for injection, and may range in severity from mild diarrhea to fatal colitis.

Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C.

difficile .

C.

difficile produces toxins A and B which contribute to the development of CDAD.

Hypertoxin producing strains of C.

difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.

CDAD must be considered in all patients who present with diarrhea following antibiotic use.

Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.

difficile may need to be discontinued.

Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C.

difficile , and surgical evaluation should be instituted as clinically indicated.

Hemorrhagic Occlusive Retinal Vasculitis (HORV) Hemorrhagic occlusive retinal vasculitis, including permanent loss of vision, occurred in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery.

The safety and efficacy of vancomycin administered by the intracameral or the intravitreal route have not been established by adequate and well-controlled trials.

Vancomycin is not indicated for the prophylaxis of endophthalmitis.

ADVERSE REACTIONS Infusion-Related Events During or soon after rapid infusion of vancomycin hydrochloride for injection, patients may develop anaphylactoid reactions, including hypotension (see ANIMAL PHARMACOLOGY ), wheezing, dyspnea, urticaria, or pruritus.

Rapid infusion may also cause flushing of the upper body (‘‘red neck’’) or pain and muscle spasm of the chest and back.

These reactions usually resolve within 20 minutes but may persist for several hours.

Such events are infrequent if vancomycin hydrochloride for injection is given by a slow infusion over 60 minutes.

In studies of normal volunteers, infusion-related events did not occur when vancomycin hydrochloride for injection was administered at a rate of 10 mg/min or less.

Nephrotoxicity 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 receiving 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 has also been reported in patients receiving vancomycin.

Gastrointestinal Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS ).

Ototoxicity A few dozen cases of hearing loss associated with 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.

Vertigo, dizziness, and tinnitus have been reported rarely.

Hematopoietic Reversible neutropenia, usually starting 1 week or more after onset of therapy with vancomycin or after a total dosage of more than 25 g, has been reported for several dozen patients.

Neutropenia appears to be promptly reversible when vancomycin is discontinued.

Thrombocytopenia has rarely been reported.

Although a causal relationship has not been established, reversible agranulocytosis (granulocytes <500/mm3) has been reported rarely.

Phlebitis Inflammation at the injection site has been reported.

Miscellaneous Patients have been reported to have had anaphylaxis, drug fever, nausea, chills, eosinophilia, rashes including exfoliative dermatitis, Stevens-Johnson syndrome (see WARNINGS , Severe Dermatologic Reactions), and vasculitis in association with the administration of vancomycin.

Chemical peritonitis has been reported following intraperitoneal administration (see PRECAUTIONS ).

Postmarketing Reports 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 possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and Subcutaneous Tissue Disorders Severe dermatologic reactions such as toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD) (see WARNINGS, Severe Dermatologic Reactions).

To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc.

at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .