Vancomycin Hydrochloride 500 mg/10mL Injection, Powder, Lyophilized, For Solution — NDC 71288-022-11 (Billing 71288-0022-11)

WARNINGS Infusion 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. 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 hydrochloride 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 hydrochloride.

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, 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 hydrochloride during or after cataract surgery. The safety and efficacy of vancomycin hydrochloride administered by the intracameral or the intravitreal route have not been established by adequate and well-controlled trials.

Vancomycin hydrochloride is not indicated for the prophylaxis of endophthalmitis.

ADVERSE REACTIONS Infusion-Related Events During or soon after rapid infusion of vancomycin hydrochloride, 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 hydrochloride 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 hydrochloride.

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 hydrochloride have been reported. Most of these patients had kidney dysfunction or a pre-existing 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 hydrochloride or after a total dosage of more than 25 grams, has been reported for several dozen patients. Neutropenia appears to be promptly reversible when vancomycin hydrochloride is discontinued.

Thrombocytopenia has rarely been reported. Although a causal relationship has not been established, reversible agranulocytosis (granulocytes <500/mm 3 ) 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 hydrochloride. Chemical peritonitis has been reported following intraperitoneal administration (see PRECAUTIONS ). Post Marketing Reports The following adverse reactions have been identified during post-approval use of vancomycin hydrochloride.

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 Meitheal Pharmaceuticals, Inc. at 1-888-808-5529 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Drug Interactions Concomitant administration of vancomycin hydrochloride and anesthetic agents has been associated with erythema and histamine-like flushing (see Pediatric Use - PRECAUTIONS ) and anaphylactoid reactions (see ADVERSE REACTIONS ) . Monitor renal function in patients receiving vancomycin hydrochloride and concurrent and/or sequential systemic or topical use of other potentially, neurotoxic and/or nephrotoxic drugs, such as amphotericin B, aminoglycosides, bacitracin, polymixin B, colistin, viomycin, or cisplatin.

PRECAUTIONS Clinically significant serum concentrations have been reported in some patients being treated for active C. difficile -induced pseudomembranous colitis after multiple oral doses of vancomycin hydrochloride. Prolonged use of vancomycin hydrochloride may result in the overgrowth of nonsusceptible microorganisms. Careful observation of the patient is essential.

If superinfection occurs during therapy, appropriate measures should be taken. In rare instances, there have been reports of pseudomembranous colitis due to C. difficile developing in patients who received intravenous vancomycin hydrochloride. Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity.

Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride (see ADVERSE REACTIONS ). Patients who will undergo prolonged therapy with vancomycin hydrochloride or those who are receiving concomitant drugs which may cause neutropenia should have periodic monitoring of the leukocyte count. Vancomycin hydrochloride for injection is irritating to tissue and must be given by a secure intravenous route of administration.

Pain, tenderness, and necrosis occur with intramuscular (IM) injection of vancomycin hydrochloride for injection or with inadvertent extravasation. Thrombophlebitis may occur, the frequency and severity of which can be minimized by administering the drug slowly as a dilute solution (2.5 to 5 g/L) and by rotation of venous access sites. There have been reports that the frequency of infusion-related events (including hypotension, flushing, erythema, urticaria, and pruritus) increases with the concomitant administration of anesthetic agents.

Infusion-related events may be minimized by the administration of vancomycin hydrochloride as a 60-minute infusion prior to anesthetic induction. The safety and efficacy of vancomycin hydrochloride administered by the intrathecal (intralumbar or intraventricular) route or by the intraperitoneal route have not been established by adequate and well controlled trials. Reports have revealed that administration of sterile vancomycin hydrochloride by the intraperitoneal route during continuous ambulatory peritoneal dialysis (CAPD) has resulted in a syndrome of chemical peritonitis.

To date, this syndrome has ranged from cloudy dialysate alone to a cloudy dialysate accompanied by variable degrees of abdominal pain and fever. This syndrome appears to be short-lived after discontinuation of intraperitoneal vancomycin hydrochloride. Prescribing vancomycin hydrochloride for injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Drug Interactions Concomitant administration of vancomycin hydrochloride and anesthetic agents has been associated with erythema and histamine-like flushing (see Pediatric Use - PRECAUTIONS ) and anaphylactoid reactions (see ADVERSE REACTIONS ) . Monitor renal function in patients receiving vancomycin hydrochloride and concurrent and/or sequential systemic or topical use of other potentially, neurotoxic and/or nephrotoxic drugs, such as amphotericin B, aminoglycosides, bacitracin, polymixin B, colistin, viomycin, or cisplatin.

Carcinogenesis, Mutagenesis, Impairment of Fertility Although no long-term studies in animals have been performed to evaluate carcinogenic potential, no mutagenic potential of vancomycin hydrochloride was found in standard laboratory tests. No definitive fertility studies have been performed. Pregnancy Teratogenic Effects Animal reproduction studies have not been conducted with vancomycin hydrochloride.

It is not known whether vancomycin hydrochloride can affect reproduction capacity. In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin hydrochloride on infants were evaluated when the drug was administered to pregna… [Excerpted — this section continues on DailyMed.]