By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first commercially available vancomycin oral liquid for the treatment of Clostridium difficile-associated diarrhea. Prior to this approval, a pharmacist compounded the oral solution. The new oral solution received priority review, orphan status, and approval under the 505(b)(2) pathway. This pathway permitted the use of clinical trial data for vancomycin capsules to support its approval, similar to a generic abbreviated new drug application (ANDA). It is marketed as Firvanq.
Vancomycin oral solution is indicated for adults and pediatric patients < 18 years of age for C. difficile-associated diarrhea (CDAD) and enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains).1
For CDAD, the recommended dose is 125 mg four times a day for 10 days for adults and 40 mg/kg in three or four divided doses for seven to 10 days for those < 18 years of age.1 The total daily dose should not exceed 2 g/day.
For Staphylococcal enterocolitis, the adult dose is 500 mg to 2 g in three or four divided doses for seven to 10 days. For those < 18 years of age, the dose is 40 mg/kg in three or four divided doses for seven to 10 days. The daily dose should not exceed 2 g/day.
Vancomycin powder for oral solution is available as 3.75 g, 7.5 g, 10.5 g, and 15 g with a grape-flavored diluent.
This is the first “ready-to-use” convenient vancomycin formulation upon reconstitution, and it does not require compounding by the pharmacy.
The most common adverse reactions are nausea (17%), abdominal pain (15%), and hypokalemia (13%).1
Vancomycin is bactericidal against C. difficile and S. aureus. Establishment of efficacy for CDAD for the oral solution was based on two trials conducted on vancomycin capsules.1,2 Adult subjects (n = 134 in trial 1 and 125 in trial 2) with CDAD were enrolled and given vancomycin at 125 mg four times a day for 10 days. CDAD was defined as ≥ 3 loose or watery bowel movements within the 24 hours preceding enrollment, and the presence of either C. difficile toxin A or B or pseudomembranes on endoscopy within the 72 hours preceding enrollment. Subjects could not have received more than 48 hours of treatment (vancomycin or metronidazole) in the five days preceding enrollment. Those with fulminant C. difficile disease, sepsis with hypotension, ileus, peritoneal signs, or severe hepatitis were excluded. The efficacy endpoint was clinical success, defined as diarrhea resolution and absence of severe abdominal discomfort due to CDAD on day 10. An analysis included all subjects who received at least one dose of vancomycin and had any post-dosing investigator evaluation data. Clinical success rates were 81.3% for trial 1 and 80.9% for trial 2. Approval via the 505(b)(2) pathway suggests comparable efficacy for the capsules and solution.
Oral vancomycin is one of two drugs (the other is fidaxomicin) recommended as first-line therapy for C. difficile infections by the Infectious Diseases Society of America.3 Because of the high cost of the oral capsules, it is common practice to prepare an oral solution from generic powder for injection.3,4 The results of a small retrospective study suggested a similar outcome with capsules compared to the compounded solution.5 However, there are several issues in compounding vancomycin, including masking the bitter taste of the drug, finding a pharmacy to provide compounding services, and insurance coverage.4 Firvanq provides an FDA-approved powder for oral solution that does not require compounding but simply reconstitution with a grape-flavored diluent. It will replace the Vancomycin Unit-of-Use Compounding Kit, first introduced in 2014. The launch of Firvanq is expected in April 2018. The cost is not yet available.6
- Firvanq Prescribing Information. CutisPharma, January 2018.
- Vancomycin Prescribing Information. ANI Pharmaceuticals, Inc., December 2017.
- McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018 Feb 15. doi: 10.1093/cid/cix1085. [Epub ahead of print].
- Walker PC, Nagel J. Clostridium difficile relapse secondary to medication access issue. Patient Safety Network, April 2014. Available at: . Accessed Feb. 23, 2018.
- Bass SN, Lam SW, Bauer SR, Neuner EA. Comparison of oral vancomycin capsule and solution for treatment of initial episode of severe Clostridium difficile infection. J Pharm Pract 2015;28:183-188.
- CutisPharma. CutisPharma announces FDA approval of Firvanq, Jan. 29, 2018. Available at: . Accessed Feb. 23, 2018.