ADVERSE REACTIONS
Clinical Trial Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to VANCOCIN in 260 adult subjects in two Phase 3 clinical trials for the treatment of diarrhea associated with C. difficile. In both trials, subjects received VANCOCIN 125 mg orally four times daily. The mean duration of treatment was 9.4 days. The median age of patients was 67, ranging between 19 and 96 years of age. Patients were predominantly Caucasian (93%) and 52% were male.
Adverse reactions occurring in ≥ 5% of VANCOCIN-treated subjects are shown in Table 1. The most common adverse reactions associated with VANCOCIN (≥ 10%) were nausea, abdominal pain, and hypokalemia.
Table 1: Common (≥ 5%) Adverse Reactionsa for VANCOCIN Reported in Clinical Trials for Treatment of Diarrhea Associated with C. difficile
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a Adverse reaction rates were derived from the incidence of treatment-emergent adverse events.
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System/Organ Class
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Adverse Reaction
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VANCOCIN
% (N=260)
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Gastrointestinal disorders
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Nausea
Abdominal pain
Vomiting
Diarrhea
Flatulence
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17
15
9
9
8
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General disorders and administration site conditions
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Pyrexia
Edema peripheral
Fatigue
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9
6
5
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Infections and infestations
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Urinary tract infection
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8
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Metabolism and nutrition disorders
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Hypokalemia
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13
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Musculoskeletal and connective tissue disorders
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Back pain
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6
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Nervous system disorders
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Headache
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7
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Nephrotoxicity (e.g., reports of renal failure, renal impairment, blood creatinine increased) occurred in 5% of subjects treated with VANCOCIN. Nephrotoxicity following VANCOCIN typically first occurred within one week after completion of treatment (median day of onset was Day 16). Nephrotoxicity following VANCOCIN occurred in 6% of subjects >65 years of age and 3% of subjects ≤65 years of age (see WARNINGS AND PRECAUTIONS, Nephrotoxicity [ 5.3 ]).
The incidences of hypokalemia, urinary tract infection, peripheral edema, insomnia, constipation, anemia, depression, vomiting, and hypotension were higher among subjects >65 years of age than in subjects ≤65 years of age (see USE IN SPECIFIC POPULATIONS, Geriatric Use [ 8.5 ]).
Discontinuation of study drug due to adverse events occurred in 7% of subjects treated with VANCOCIN. The most common adverse events leading to discontinuation of VANCOCIN were C. difficile colitis (<1%), nausea (<1%), and vomiting (<1%).
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of VANCOCIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
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 (see WARNINGS AND PRECAUTIONS, Ototoxicity [ 5.4 ]). Vertigo, dizziness, and tinnitus have been reported.
Hematopoietic: Reversible neutropenia, usually starting 1 week or more after onset of intravenous therapy with vancomycin or after a total dose of more than 25 g, has been reported for several dozen patients. Neutropenia appears to be promptly reversible when vancomycin is discontinued. Thrombocytopenia has been reported.
Miscellaneous: Patients have been reported to have had anaphylaxis, drug fever, chills, nausea, eosinophilia, rashes (including exfoliative dermatitis), Stevens-Johnson syndrome, toxic epidermal necrolysis, and rare cases of 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.
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