Prescription Drug Information: FIRVANQ (Page 3 of 4)

12.4 Microbiology

Mechanism of Action

The bactericidal action of vancomycin against the vegetative cells of C. difficile and S. aureus results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis.

Mechanism of Resistance

C. difficile

Isolates of C. difficile generally have vancomycin minimal inhibitory concentrations (MICs) of < 1 mcg/mL; however, vancomycin MICs ranging from 4 mcg/mL to 16 mcg/mL have been reported. The mechanism which mediates C. difficile ‘s decreased susceptibility to vancomycin has not been fully elucidated.

S. aureus

S. aureus isolates with vancomycin MICs as high as 1024 mcg/mL have been reported. The exact mechanism of this resistance is not clear but is believed to be due to cell wall thickening and potentially the transfer of genetic material.

Vancomycin has been shown to be active against susceptible isolates of the following bacteria in clinical infections [ see Indications and Usage ( 1) ].

Anaerobic gram-positive bacteria
C . difficile isolates associated with C. difficile -associated diarrhea.

Gram-positive bacteria S . aureus (including methicillin-resistant isolates) associated with enterocolitis.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term carcinogenesis studies in animals have been conducted.

At concentrations up to 1000 mcg/mL, vancomycin had no mutagenic effect in vitro in the mouse lymphoma forward mutation assay or the primary rat hepatocyte unscheduled DNA synthesis assay. The concentrations tested in vitro were above the peak plasma vancomycin concentrations of 20 to 40 mcg/mL usually achieved in humans after slow infusion of the maximum recommended dose of 1 g. Vancomycin had no mutagenic effect in vivo in the Chinese hamster sister chromatid exchange assay (400 mg/kg IP) or the mouse micronucleus assay (800 mg/kg IP).

No definitive fertility studies have been conducted.

14 CLINICAL STUDIES

14.1 Diarrhea As sociated with Clostridium difficile

In two trials, vancomycin hydrochloride 125 mg orally four times daily for 10 days was evaluated in 266 adult subjects with C. difficile -associated diarrhea (CDAD). Enrolled subjects were 18 years of age or older and received no more than 48 hours of treatment with oral vancomycin hydrochloride or oral/intravenous metronidazole in the 5 days preceding enrollment. 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 with fulminant C. difficile disease, sepsis with hypotension, ileus, peritoneal signs or severe hepatic disease were excluded.

Efficacy analyses were performed on the Full Analysis Set (FAS), which included randomized subjects who received at least one dose of vancomycin hydrochloride and had any post-dosing investigator evaluation data (N = 259; 134 in Trial 1 and 125 in Trial 2).

The demographic profile and baseline CDAD characteristics of enrolled subjects were similar in the two trials. Vancomycin hydrochloride-treated subjects had a median age of 67 years, were mainly white (93%), and male (52%). CDAD was classified as severe (defined as 10 or more unformed bowel movements per day or white blood cell count (WBC) ≥ 15000/mm 3) in 25% of subjects, and 47% were previously treated for CDAD.

Efficacy was assessed by using clinical success, defined as diarrhea resolution and the absence of severe abdominal discomfort due to CDAD, on Day 10. An additional efficacy endpoint was the time to resolution of diarrhea, defined as the beginning of diarrhea resolution that was sustained through the end of the prescribed active treatment period.

The results for clinical success for vancomycin hydrochloride-treated subjects in both trials are shown in Table 4.

Table 4: Clinical Success Rates (Full Analysis Set)
Clinical Success Rate Vancomycin Hydrochloride % (N) 95% Confidence Interval
Trial 1 81.3 (134) (74.4, 88.3)
Trial 2 80.8 (125) (73.5, 88.1)

The median time to resolution of diarrhea was 5 days and 4 days in Trial 1 and Trial 2, respectively. For subjects older than 65 years of age, the median time to resolution was 6 days and 4 days in Trial 1 and Trial 2, respectively. In subjects with diarrhea resolution at end-of-treatment with vancomycin hydrochloride, recurrence of CDAD during the following four weeks occurred in 25 of 107 (23%) and 18 of 102 (18%) in Trial 1 and Trial 2, respectively.

Restriction Endonuclease Analysis (REA) was used to identify C. difficile baseline isolates in the BI group. In Trial 1, the vancomycin hydrochloride-treated subjects were classified at baseline as follows 31 (23%) with BI strain, 69 (52%) with non-BI strain, and 34 (25%) with unknown strain. Clinical success rates were 87% for BI strain, 81% for non-BI strain, and 76% for unknown strain. In subjects with diarrhea resolution at end-of-treatment with vancomycin hydrochloride, recurrence of CDAD during the following four weeks occurred in 7 of 26 subjects with BI strain, 12 of 56 subjects with non-BI strain, and 6 of 25 subjects with unknown strain.

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Each FIRVANQ kit contains a bottle of vancomycin hydrochloride USP, as white to almost white or tan to brown powder for oral solution, and a bottle of pre-measured Grape-Flavored Diluent, in the strengths and volumes listed in Table 5.

Table 5: Vancomycin Strength, Diluent Volume and National Drug Code (NDC) Numbers
Vancomycin S trength per B ottle Diluent for FIRVANQ NDC Numbers
3.75 g 147 mL 65628-204-05
7.5 g 295 mL 65628-205-10
7.5 g 145 mL 65628-206-05
15 g 289 mL 65628-208-10

Storage and Handling

Store FIRVANQ Kit prior and reconstituted solution at refrigerated conditions, 2°C to 8°C (36°F to 46°F).

Discard the reconstituted solution after 14 days, or if it appears hazy or contains particulates.

Do not freeze. Keep container tightly closed. Protect from light.

[ see Dosage and Administration ( 2.4) ].

17 PATIENT COUNSELING INFORMATION

Antibacterial Resistance

Patients should be counseled that antibacterial drugs including FIRVANQ should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When FIRVANQ 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 FIRVANQ or other antibacterial drugs in the future.

Important Administration Instructions

Instruct the patient or caregiver to:

  • Shake the reconstituted solutions of FIRVANQ well before each use and to use an oral dosing device that measures the appropriate volume of the oral solution in milliliters.
  • Store the reconstituted solutions of FIRVANQ in the refrigerator (with temperatures set to between 2°C to 8°C (36°F to 46°F)) when not in use.
  • Discard reconstituted solutions of FIRVANQ after 14 days, or if it appears hazy or contains particulates.

Manufactured for:

841 Woburn St.
Wilmington, MA 01887 USA

PRINCIPAL DISPLAY PANEL

NDC 65628-015-05
FIRVANQ
(vancomycin hydrochloride) for oral solution
For Oral Use O nly
Vancomycin Hydrochloride Powder for Oral Solution Kit
Vancomycin 25 mg/mL in Grape Flavored Diluent
EACH KIT INCLUDES:
• 1 bottle containing Vancomycin Hydrochloride USP,
powder for oral solution, equivalent to 3.75 g Vancomycin
• 1 bottle containing 147 mL Grape Flavored Diluent
for reconstitution
When reconstituted, each mL contains 25 mg Vancomycin
Must be Refrigerated
150 mL
final volume after reconstitution Rx Only

Firvanq 25 mg/ml 150 mL
(click image for full-size original)

PRINCIPAL DISPLAY PANEL

NDC 65628-015-10
FIRVANQ
(vancomycin hydrochloride) for oral solution
For Oral Use Only
Vancomycin Hydrochloride Powder for Oral Solution Kit
Vancomycin 25 mg/mL in Grape Flavored Diluent
EACH KIT INCLUDES:
• 1 bottle containing Vancomycin Hydrochloride USP,
powder for oral solution, equivalent to 7.5 g Vancomycin
• 1 bottle containing 295 mL Grape Flavored Diluent
for reconstitution
When reconstituted, each mL contains 25 mg Vancomycin
Must be Refrigerated
300 mL
final volume after reconstitution Rx Only

Firvanq 25 mg/ml 300 mL
(click image for full-size original)

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

Medication Sections

Medication Information by RSS

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2020. All Rights Reserved.