The most common adverse reactions (≥ 10%) were nausea (17%), abdominal pain (15%), and hypokalemia (13%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-800-308-6755 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials 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 vancomycin in 260 adult subjects in two Phase 3 clinical trials for the treatment of diarrhea associated with C. difficile .
In both trials, subjects received vancomycin 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 vancomycin-treated subjects are shown in Table 1. The most common adverse reactions associated with vancomycin (≥ 10%) were nausea, abdominal pain, and hypokalemia.
Table 1: Common ( ≥ 5%) Adverse Reactions a for Vancomycin Reported in Clinical Trials for Treatment of Diarrhea Associated with C. difficile a Adverse reaction rates were derived from the incidence of treatment-emergent adverse events. System/Organ Class Adverse Reaction Vancomycin % (N=260) Gastrointestinal disorders Nausea Abdominal pain Vomiting Diarrhea Flatulence 17 15 9 9 8 General disorders and administration site conditions Pyrexia Edema peripheral Fatigue 9 6 5 Infections and infestations Urinary tract infection 8 Metabolism and nutrition disorders Hypokalemia 13 Musculoskeletal and connective tissue disorders Back pain 6 Nervous system disorders Headache 7 Nephrotoxicity (e.g., reports of renal failure, renal impairment, blood creatinine increased) occurred in 5% of subjects treated with vancomycin.
Nephrotoxicity following vancomycin typically first occurred within one week after completion of treatment (median day of onset was Day 16). Nephrotoxicity following vancomycin occurred in 6% of subjects >65 years of age and 3% of subjects ≤65 years of age [see Warnings and Precautions ( 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 ( 8.5 )] .
Discontinuation of study drug due to adverse events occurred in 7% of subjects treated with vancomycin. The most common adverse events leading to discontinuation of vancomycin were C. difficile colitis (<1%), nausea (<1%), and vomiting (<1%).
6.2Postmarketing Experience
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 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 ( 5.4 )] .
Vertigo, dizziness, and tinnitus have been reported. 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 IgA bullous dermatosis (LABD) [see Warnings and Precautions ( 5.5 )] , rashes (including exfoliative dermatitis).
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, and 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 (“vancomycin infusion reaction”), pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes but may persist for several hours.
