Label: VANCOMYCIN HYDROCHLORIDE powder, for solution

Microbiology

The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis.

NOTE: The oral form of vancomycin is effective only for the infections noted in the INDICATIONS AND USAGE section. The oral form is not effective for any other type of infection.

Vancomycin has been shown to be active against most strains of the following microorganisms in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic gram-positive microorganisms
Staphylococcus aureus (including methicillin-resistant strains) associated with enterocolitis

Aerobic gram-positive microorganisms
Clostridium difficile antibiotic-associated pseudomembranous colitis

Nephrotoxicity

Nephrotoxicity (e.g., reports of renal failure, renal impairment, blood creatinine increased) has occurred following oral vancomycin hydrochloride therapy in randomized controlled clinical trials, and can occur either during or after completion of therapy. The risk of nephrotoxicity is increased in patients over 65 years of age.

In patients over 65 years of age, including those with normal renal function prior to treatment, renal function should be monitored during and following treatment with vancomycin oral solution to detect potential vancomycin induced nephrotoxicity.

Ototoxicity

Ototoxicity has occurred in patients receiving vancomycin. It may be transient or permanent. It has been reported mostly in patients who have been given excessive intravenous doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside. Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity.

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 Oral Solution at the first appearance of signs and symptoms of TEN, SJS, DRESS, AGEP, or LABD.

Clostridium Difficile Associated Diarrhea (CDAD)

Significant systemic absorption has been reported in some patients (e.g., patients with renal insufficiency and/or colitis) who have taken multiple oral doses of vancomycin hydrochloride for C. difficile-associated diarrhea. In these patients, serum vancomycin concentrations reached therapeutic levels for the treatment of systemic infections. Some patients with inflammatory disorders of the intestinal mucosa also may have significant systemic absorption of vancomycin. These patients may be at risk for the development of adverse reactions associated with higher doses of vancomycin oral solution; therefore, monitoring of serum concentrations of vancomycin may be appropriate in some instances, e.g., in patients with renal insufficiency and/or colitis or in those receiving concomitant therapy with an aminoglycoside antibacterial drug.

Pregnancy

Animal reproduction studies have not been conducted with vancomycin. It is not known 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 intravenously to pregnant women for serious staphylococcal infections complicating intravenous drug abuse. Vancomycin was found in cord blood. No sensorineural hearing loss or nephrotoxicity attributable to vancomycin was noted. One infant whose mother received vancomycin in the third trimester experienced conductive hearing loss that was not attributed to the administration of vancomycin. Because the number of patients treated in this study was limited and vancomycin was administered only in the second and third trimesters, it is not known whether vancomycin causes fetal harm. Vancomycin Hydrochloride for Oral Solution should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Vancomycin is excreted in human milk based on information obtained with the intravenous administration of vancomycin. However, systemic absorption of vancomycin is very low following oral administration of Vancomycin Hydrochloride for Oral Solution (see CLINICAL PHARMACOLOGY). It is not known whether oral vancomycin is excreted in human milk, as no studies of vancomycin concentration in human milk after oral administration have been done. Caution should be exercised when Vancomycin Hydrochloride for Oral Solution is administered to a nursing woman. Because of the potential for adverse events, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Geriatric Use

In clinical trials, 54% of vancomycin hydrochloride-treated subjects were > 65 years of age. Of these, 40% were between the ages of > 65 and 75, and 60% were > 75 years of age.

Clinical studies with vancomycin hydrochloride in C. difficile-associated diarrhea have demonstrated that geriatric subjects are at increased risk of developing nephrotoxicity following treatment with oral vancomycin hydrochloride, which may occur during or after completion of therapy. In patients over 65 years of age, including those with normal renal function prior to treatment, renal function should be monitored during and following treatment with vancomycin hydrochloride to detect potential vancomycin induced nephrotoxicity.

Patients over 65 years of age may take longer to respond to therapy compared to patients 65 years of age and younger. Clinicians should be aware of the importance of appropriate duration of vancomycin hydrochloride treatment in patients over 65 years of age and not discontinue or switch to alternative treatment prematurely.

Information for Patients

Severe Dermatologic Reactions
Advise patients about the signs and symptoms of serious skin manifestations. Instruct patients to stop taking Vancocin immediately and promptly seek medical attention at the first signs or symptoms of skin rash, mucosal lesions and blisters (see WARNINGS).

Patients should be counseled that antibacterial drugs including Vancomycin Hydrochloride for Oral Solution should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Vancomycin Hydrochloride for Oral Solution is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Vancomycin Hydrochloride for Oral Solution or other antibacterial drugs in the future.

Nephrotoxicity

Nephrotoxicity (e.g., reports of renal failure, renal impairment, blood creatinine increased) occurred in 5% of subjects treated with vancomycin hydrochloride. Nephrotoxicity following vancomycin hydrochloride typically first occurred within one week after completion of treatment (median day of onset was Day 16). Nephrotoxicity following vancomycin hydrochloride occurred in 6% of subjects over 65 years of age and 3% of subjects 65 years of age and younger. Nephrotoxicity can also occur during oral vancomycin administration.

The incidences of hypokalemia, urinary tract infection, peripheral edema, insomnia, constipation, anemia, depression, vomiting, and hypotension were higher among subjects over 65 years of age than in subjects 65 years of age and younger.

Discontinuation of study drug due to adverse events occurred in 7% of subjects treated with vancomycin hydrochloride. The most common adverse events leading to discontinuation of vancomycin hydrochloride were C. difficile colitis (< 1%), nausea (< 1%), and vomiting (< 1%).

Ototoxicity

Cases of hearing loss associated with intravenously administered 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 intravenous 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.

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.

A condition has been reported that is similar to the IV-induced syndrome with symptoms consistent with anaphylactoid reactions, including hypotension, wheezing, dyspnea, urticaria, pruritus, flushing of the upper body (“Red Man Syndrome”), pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes but may persist for several hours.

Post Marketing Reports

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).

Adults

Vancomycin Hydrochloride for Oral Solution is used in treating antibiotic-associated pseudomembranous colitis caused by C. difficile and staphylococcal enterocolitis. Vancomycin Hydrochloride for Oral Solution is not effective by the oral route for other types of infections. The usual adult total daily dosage is 500 mg to 2 g administered orally in 3 or 4 divided doses for 7 to 10 days.

Pediatric Patients

The usual daily dosage is 40 mg/kg in 3 or 4 divided doses for 7 to 10 days. The total daily dosage should not exceed 2 g.