FDA Label for Dalvance
View Indications, Usage & Precautions
- 1.1 ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS
- 1.2 USAGE
- 2.1 RECOMMENDED DOSAGE REGIMEN
- 2.2 DOSAGE IN PATIENTS WITH RENAL IMPAIRMENT
- 2.3 PREPARATION AND ADMINISTRATION
- 3 DOSAGE FORMS AND STRENGTHS
- 4 CONTRAINDICATIONS
- 5.1 HYPERSENSITIVITY REACTIONS
- 5.2 INFUSION-RELATED REACTIONS
- 5.3 HEPATIC EFFECTS
- 5.4 CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA
- 5.5 DEVELOPMENT OF DRUG-RESISTANT BACTERIA
- 6.1 CLINICAL TRIALS EXPERIENCE
- 7.1 DRUG-LABORATORY TEST INTERACTIONS
- 7.2 DRUG-DRUG INTERACTIONS
- 8.4 PEDIATRIC USE
- 8.5 GERIATRIC USE
- 8.6 RENAL IMPAIRMENT
- 8.7 HEPATIC IMPAIRMENT
- 10 OVERDOSAGE
- 11 DESCRIPTION
- 12.1 MECHANISM OF ACTION
- 12.2 PHARMACODYNAMICS
- 12.3 PHARMACOKINETICS
- 13.1 CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
- 13.2 ANIMAL TOXICOLOGY AND/OR PHARMACOLOGY
- 14 CLINICAL STUDIES
- 15 REFERENCES
- 16 HOW SUPPLIED/STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
Dalvance Product Label
The following document was submitted to the FDA by the labeler of this product Allergan, Inc.. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.
1.1 Acute Bacterial Skin And Skin Structure Infections
DALVANCE® (dalbavancin) for injection is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI), caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (including S. anginosus, S. intermedius, S. constellatus) and Enterococcus faecalis (vancomycin susceptible strains).
1.2 Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of DALVANCE and other antibacterial agents, DALVANCE should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
2.1 Recommended Dosage Regimen
The recommended dosage regimen of DALVANCE in patients with normal renal function is 1500 mg, administered either as a single dose, or 1000 mg followed one week later by 500 mg. DALVANCE should be administered over 30 minutes by intravenous infusion [see Dosage and Administration (2.3)].
2.2 Dosage In Patients With Renal Impairment
In patients with renal impairment whose known creatinine clearance is less than 30 mL/min and who are not receiving regularly scheduled hemodialysis, the recommended regimen of DALVANCE is 1125 mg, administered as a single dose, or 750 mg followed one week later by 375 mg (see Table 1). No dosage adjustment is recommended for patients receiving regularly scheduled hemodialysis, and DALVANCE can be administered without regard to the timing of hemodialysis [see Use in Specific Populations (8.5), Clinical Pharmacology (12.3)].
* as calculated using the Cockcroft-Gault formula | ||
** administered intravenously over 30 minutes | ||
Estimated CrCl* | DALVANCE Single Dose Regimen** | DALVANCE Two-Dose Regimen** |
≥ 30 mL/min or on regular hemodialysis | 1500 mg | 1000 mg followed one week later by 500 mg |
< 30 mL/min and not on regular hemodialysis | 1125 mg | 750 mg followed one week later by 375 mg |
2.3 Preparation And Administration
DALVANCE (dalbavancin) for injection must be reconstituted with either Sterile Water for Injection, USP, or 5% Dextrose Injection, USP, and subsequently diluted only with 5% Dextrose Injection, USP, to a final concentration of 1 mg/mL to 5 mg/mL.
Reconstitution: DALVANCE must be reconstituted under aseptic conditions, using 25 mL of either Sterile Water for Injection, USP, or 5% Dextrose Injection, USP, for each 500 mg vial. To avoid foaming, alternate between gentle swirling and inversion of the vial until its contents are completely dissolved. Do not shake. The reconstituted vial contains 20 mg/mL dalbavancin as a clear, colorless to yellow solution.
Reconstituted vials may be stored either refrigerated at 2 to 8 °C (36 to 46 °F), or at controlled room temperature 20 to 25 °C (68 to 77 °F). Do not freeze.
Dilution: Aseptically transfer the required dose of reconstituted dalbavancin solution from the vial(s) to an intravenous bag or bottle containing 5% Dextrose Injection, USP. The diluted solution must have a final dalbavancin concentration of 1 mg/mL to 5 mg/mL. Discard any unused portion of the reconstituted solution.
Once diluted into an intravenous bag or bottle as described above, DALVANCE may be stored either refrigerated at 2 to 8 °C (36 to 46 °F) or at a controlled room temperature of 20 to 25 °C (68 to 77 °F). Do not freeze.
The total time from reconstitution to dilution to administration should not exceed 48 hours.
Like all parenteral drug products, diluted DALVANCE should be inspected visually for particulate matter prior to infusion. If particulate matter is identified, do not use.
Administration: After reconstitution and dilution, DALVANCE is to be administered via intravenous infusion, using a total infusion time of 30 minutes.
Do not co-infuse DALVANCE with other medications or electrolytes. Saline-based infusion solutions may cause precipitation and should not be used. The compatibility of reconstituted DALVANCE with intravenous medications, additives, or substances other than 5% Dextrose Injection, USP has not been established.
If a common intravenous line is being used to administer other drugs in addition to DALVANCE, the line should be flushed before and after each DALVANCE infusion with 5% Dextrose Injection, USP.
3 Dosage Forms And Strengths
DALVANCE is supplied in clear glass vials containing sterile powder (white/off-white to pale yellow) equivalent to 500 mg of dalbavancin.
4 Contraindications
DALVANCE is contraindicated in patients with known hypersensitivity to dalbavancin. No data are available on cross-reactivity between dalbavancin and other glycopeptides, including vancomycin.
5.1 Hypersensitivity Reactions
Serious hypersensitivity (anaphylactic) and skin reactions have been reported in patients treated with DALVANCE. If an allergic reaction occurs, treatment with DALVANCE should be discontinued. Before using DALVANCE, inquire carefully about previous hypersensitivity reactions to glycopeptides, and due to the possibility of cross-sensitivity, exercise caution in patients with a history of glycopeptide allergy [see Patient Counseling Information (17)].
5.2 Infusion-Related Reactions
DALVANCE is administered via intravenous infusion, using a total infusion time of 30 minutes to minimize the risk of infusion-related reactions. Rapid intravenous infusions of DALVANCE can cause reactions that resemble “Red-Man Syndrome,” including flushing of the upper body, urticaria, pruritus, and/or rash. Stopping or slowing the infusion may result in cessation of these reactions.
5.3 Hepatic Effects
In Phase 2 and 3 clinical trials, more DALVANCE than comparator-treated subjects with normal baseline transaminase levels had post-baseline alanine aminotransferase (ALT) elevation greater than 3 times the upper limit of normal (ULN). Overall, abnormalities in liver tests (ALT, AST, bilirubin) were reported with similar frequency in the DALVANCE and comparator arms [see Adverse Reactions (6.1)].
5.4 Clostridium Difficile-Associated Diarrhea
Clostridium difficile-associated diarrhea (CDAD) has been reported in users of nearly all systemic antibacterial drugs, including DALVANCE, with severity ranging from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon, and may permit overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile should be discontinued, if possible. Appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
5.5 Development Of Drug-Resistant Bacteria
Prescribing DALVANCE in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of DALVANCE cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice.
Adverse reactions were evaluated for 2473 patients treated with DALVANCE: 1778 patients were treated with DALVANCE in seven Phase 2/3 trials comparing DALVANCE to comparator antibacterial drugs and 695 patients were treated with DALVANCE in one Phase 3 trial comparing DALVANCE single and two-dose regimens. A causal relationship between study drug and adverse reactions was not always established. The median age of patients treated with DALVANCE was 48 years, ranging between 16 and 93 years. Patients treated with DALVANCE were predominantly male (59.5%) and White (81.2%).
7.1 Drug-Laboratory Test Interactions
Drug-laboratory test interactions have not been reported. DALVANCE at therapeutic concentrations does not artificially prolong prothrombin time (PT) or activated partial thromboplastin time (aPTT).
7.2 Drug-Drug Interactions
No clinical drug-drug interaction studies have been conducted with DALVANCE. There is minimal potential for drug-drug interactions between DALVANCE and cytochrome P450 (CYP450) substrates, inhibitors, or inducers [see Clinical Pharmacology (12.3)].
8.4 Pediatric Use
Safety and efficacy in pediatric patients have not been established.
8.5 Geriatric Use
Of the 2473 patients treated with DALVANCE in Phase 2 and 3 clinical trials, 403 patients (16.3%) were 65 years of age or older. The efficacy and tolerability of DALVANCE were similar to comparator regardless of age. The pharmacokinetics of DALVANCE was not significantly altered with age; therefore, no dosage adjustment is necessary based on age alone.
DALVANCE is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in this age group.
8.6 Renal Impairment
In patients with renal impairment whose known creatinine clearance is less than 30 mL/min and who are not receiving regularly scheduled hemodialysis, the recommended regimen for DALVANCE is 1125 mg, administered as a single dose, or 750 mg followed one week later by 375 mg. No dosage adjustment is recommended for patients receiving regularly scheduled hemodialysis, and DALVANCE can be administered without regard to the timing of hemodialysis [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
No dosage adjustment of DALVANCE is recommended for patients with mild hepatic impairment (Child-Pugh Class A). Caution should be exercised when prescribing DALVANCE to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C) as no data are available to determine the appropriate dosing in these patients [see Clinical Pharmacology (12.3)].
10 Overdosage
Specific information is not available on the treatment of overdose with DALVANCE, as dose-limiting toxicity has not been observed in clinical studies. In Phase 1 studies, healthy volunteers have been administered cumulative doses of up to 4500 mg over a period of up to 8 weeks, with no signs of toxicity or laboratory results of clinical concern.
Treatment of overdose with DALVANCE should consist of observation and general supportive measures. Although no information is available specifically regarding the use of hemodialysis to treat overdose, in a Phase 1 study in patients with renal impairment less than 6% of the recommended dalbavancin dose was removed [see Clinical Pharmacology (12.3)].
11 Description
DALVANCE (dalbavancin) for injection is a lipoglycopeptide synthesized from a fermentation product of Nonomuraea species.
Dalbavancin is a mixture of five closely related active homologs (A0, A1, B0, B1, and B2); the component B0 is the major component of dalbavancin. The homologs share the same core structure and differ in the fatty acid side chain of the N-acylaminoglucuronic acid moiety (R1) structure and/or the presence of an additional methyl group (R2) on the terminal amino group (shown in the Figure 1 and Table 3 below).
*Anhydrous free base | ||||
Dalbavancin | R1 | R2 | Molecular Formula | Molecular Weight* |
A0 | CH(CH3)2 | H | C87H98N10O28Cl2 ⋅ 1.6 HCl | 1802.7 |
A1 | CH2CH2CH3 | H | C87H98N10O28Cl2 ⋅ 1.6 HCl | 1802.7 |
B0 | CH2CH(CH3)2 | H | C88H100N10O28Cl2 ⋅ 1.6 HCl | 1816.7 |
B1 | CH2CH2CH2CH3 | H | C88H100N10O28Cl2 ⋅ 1.6 HCl | 1816.7 |
B2 | CH2CH(CH3)2 | CH3 | C89H102N10O28Cl2 ⋅ 1.6 HCl | 1830.7 |
The B0 INN chemical name is: 5,31-dichloro-38-de(methoxycarbonyl)-7-demethyl-19-deoxy-56-O-[2-deoxy-2-[(10-methylundecanoyl)amino]-β-D-glucopyranuronosyl]-38-[[3-(dimethylamino)propyl] carbamoyl]-42-O-α-D-mannopyranosyl-15-N-methyl(ristomycin A aglycone) hydrochloride.
DALVANCE is supplied in clear glass vials as a sterile, lyophilized, preservative-free, white to off-white to pale yellow solid. Each vial contains dalbavancin HCl equivalent to 500 mg of dalbavancin as the free base, plus lactose monohydrate (129 mg) and mannitol (129 mg) as excipients. Sodium hydroxide or hydrochloric acid may be added to adjust the pH at the time of manufacture. The powder is to be reconstituted and further diluted for IV infusion [see Dosage and Administration (2.3), How Supplied/Storage and Handling (16)].
12.1 Mechanism Of Action
Dalbavancin is an antibacterial drug [see Microbiology (12.4)].
12.2 Pharmacodynamics
The antibacterial activity of dalbavancin appears to best correlate with the ratio of area under the concentration-time curve to minimal inhibitory concentration (AUC/MIC) for Staphylococcus aureus based on animal models of infection. An exposure-response analysis of a single study in patients with complicated skin and skin structure infections supports the two-dose regimen [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)].
12.3 Pharmacokinetics
Dalbavancin pharmacokinetic parameters have been characterized in healthy subjects, patients, and specific populations. Pharmacokinetic parameters following administration of single intravenous 1000 mg and 1500 mg doses were as shown in Table 4. The pharmacokinetics of dalbavancin can be described using a three-compartment model.
All values are presented as mean (% coefficient of variation) | ||
1 Data from 50 healthy subjects. | ||
2 Data from 12 healthy subjects. | ||
3 Based upon population pharmacokinetic analyses of data from patients, the effective half-life is approximately 8.5 days (204 hours). | ||
4 Data from 49 healthy subjects. | ||
Abbreviation: ND – not determined | ||
Parameter | Single 1000 mg Dose | Single 1500 mg Dose |
Cmax (mg/L) | 287 (13.9)1 | 423 (13.2)4 |
AUC0-24 (mg•h/L) | 3185 (12.8)1 | 4837 (13.7)4 |
AUC0-Day7 (mg•h/L) | 11160 (41.1)2 | ND |
AUC0-inf (mg•h/L) | 23443 (40.9)2 | ND |
Terminal t½ (h) | 346 (16.5)2,3 | ND |
CL (L/h) | 0.0513 (46.8)2 | ND |
In healthy subjects, dalbavancin AUC0-24h and Cmax both increased proportionally to dose following single IV dalbavancin doses ranging from 140 mg to 1500 mg, indicating linear pharmacokinetics.
The mean plasma concentration-time profile for dalbavancin following the recommended two-dose regimen of 1000 mg followed one week later by 500 mg is shown in Figure 2.
No apparent accumulation of dalbavancin was observed following multiple IV infusions administered once weekly for up to eight weeks, with 1000 mg on Day 1 followed by up to seven weekly 500 mg doses, in healthy adults with normal renal function.
13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals to determine the carcinogenic potential of dalbavancin have not been conducted.
Dalbavancin was not genotoxic in a bacterial reverse mutation (Ames) assay, a mammalian HGPRT gene mutation assay, an in vitro chromosome aberration assay in Chinese Hamster Ovary cells, or an in vivo mouse micronucleus assay.
Impaired fertility in the rat was not observed at a dose of 15 mg/kg/day (1.2 times the human dose on an exposure basis). Reductions in male and female fertility and increased embryo resorptions occurred at a dose of 45 mg/kg/day (3.5 times the human dose on an exposure basis), at which signs of parental toxicity were also observed.
13.2 Animal Toxicology And/Or Pharmacology
Increases in serum levels of liver enzymes (ALT, AST), associated with microscopic findings in the liver were noted in toxicology studies in rats and dogs where dalbavancin was administered daily for 28 to 90 days. Hepatocellular necrosis was observed in dogs dosed at ≥10 mg/kg/day for longer than 2 months, i.e., at approximately 5 to 7 times the expected human dose on an exposure basis. Histiocytic vacuolation and hepatocyte necrosis were observed in rats dosed daily at 40 and 80 mg/kg/day, respectively, for 4 weeks, (approximately 3 and 6 times the expected human dose on an exposure basis, respectively). In addition, renal toxicity characterized by increases in serum BUN and creatinine and microscopic kidney findings was observed in rats and dogs at doses 5 to 7 times the expected human dose on an exposure basis. The relationship between these findings in the animal toxicology studies after 28 and 90 consecutive days of dosing to the indicated clinical dosing of 2 doses 7 days apart are unclear.
14 Clinical Studies
Acute Bacterial Skin and Skin Structure Infections:
DALVANCE Two-dose Regimen (1000 mg Day 1; 500 mg Day 8)
Adult patients with ABSSSI were enrolled in two Phase 3, randomized, double-blind, double-dummy clinical trials of similar design (Trial 1 and Trial 2). The Intent-to-Treat (ITT) population included 1,312 randomized patients. Patients were treated for two weeks with either a two-dose regimen of intravenous DALVANCE (1000 mg followed one week later by 500 mg) or intravenous vancomycin (1000 mg or 15 mg/kg every 12 hours, with the option to switch to oral linezolid after 3 days). DALVANCE-treated patients with creatinine clearance of less than 30 mL/min received 750 mg followed one week later by 375 mg. Approximately 5% of patients also received a protocol-specified empiric course of treatment with intravenous aztreonam for coverage of Gram-negative pathogens.
The specific infections in these trials included cellulitis (approximately 50% of patients across treatment groups), major abscess (approximately 30%), and wound infection (approximately 20%). The median lesion area at baseline was 341 cm2. In addition to local signs and symptoms of infection, patients were also required to have at least one systemic sign of disease at baseline, defined as temperature 38°C or higher (approximately 85% of patients), white blood cell count greater than 12,000 cells/mm3 (approximately 40%), or 10% or more band forms on white blood cell differential (approximately 23%). Across both trials, 59% of patients were from Eastern Europe and 36% of patients were from North America. Approximately 89% of patients were Caucasian and 58% were males. The mean age was 50 years and the mean body mass index was 29.1 kg/m2.
The primary endpoint of these two ABSSSI trials was the clinical response rate where responders were defined as patients who had no increase from baseline in lesion area 48 to 72 hours after initiation of therapy, and had a temperature consistently at or below 37.6° C upon repeated measurement. Table 7 summarizes overall clinical response rates in these two ABSSSI trials using the pre-specified primary efficacy endpoint in the ITT population.
DALVANCE n/N (%) | Vancomycin/Linezolid n/N (%) | Difference (95% CI)3 | |
Trial 1 | 240/288 (83.3) | 233/285 (81.8) | 1.5 (-4.6, 7.9) |
Trial 2 | 285/371 (76.8) | 288/368 (78.3) | -1.5 (-7.4, 4.6) |
1 There were 7 patients who did not receive treatment and were counted as non-responders: 6 DALVANCE patients (3 in each trial) and one vancomycin/linezolid patient in Trial 2. | |||
2 Patients who died or used non-study antibacterial therapy or had missing measurements were classified as non-responders. | |||
3 The 95% Confidence Interval (CI) is computed using the Miettinen and Nurminen approach, stratified by baseline fever status. |
A key secondary endpoint in these two ABSSSI trials evaluated the percentage of ITT patients achieving a 20% or greater reduction in lesion area from baseline at 48-72 hours after initiation of therapy. Table 8 summarizes the findings for this endpoint in these two ABSSSI trials.
DALVANCE n/N (%) | Vancomycin/Linezolid n/N (%) | Difference (95% CI)3 | |
Trial 1 | 259/288 (89.9) | 259/285 (90.9) | -1.0 (-5.7, 4.0) |
Trial 2 | 325/371 (87.6) | 316/368 (85.9) | 1.7 (-3.2, 6.7) |
1 There were 7 patients (as described in Table 7) who did not receive treatment and were counted as non-responders. | |||
2 Patients who died or used non-study antibacterial therapy or had missing measurements were classified as non-responders. | |||
3 The 95% CI is computed using the Miettinen and Nurminen approach, stratified by baseline fever status. |
Another secondary endpoint in these two ABSSSI trials was the clinical success rate assessed at a follow-up visit occurring between Days 26 to 30. Clinical Success at this visit was defined as having a decrease in lesion size (both length and width measurements), a temperature of 37.6° C or lower, and meeting pre-specified criteria for local signs: purulent discharge and drainage absent or mild and improved from baseline, heat/warmth & fluctuance absent, swelling/induration & tenderness to palpation absent or mild.
Table 9 summarizes clinical success rates at a follow-up visit for the ITT and clinically evaluable population in these two ABSSSI trials. Note that there are insufficient historical data to establish the magnitude of drug effect for antibacterial drugs compared with placebo at the follow-up visits. Therefore, comparisons of DALVANCE to vancomycin/linezolid based on clinical success rates at these visits cannot be utilized to establish non-inferiority.
DALVANCE n/N (%) | Vancomycin/Linezolid n/N (%) | Difference (95%CI)3 | |
Trial 1 | |||
ITT | 241/288 (83.7%) | 251/285 (88.1%) | -4.4% (-10.1, 1.4) |
CE | 212/226 (93.8%) | 220/229 (96.1%) | -2.3% (-6.6, 2.0) |
Trial 2 | |||
ITT | 327/371 (88.1%) | 311/368 (84.5%) | 3.6% (-1.3, 8.7) |
CE | 283/294 (96.3%) | 257/272 (94.5%) | 1.8% (-1.8, 5.6) |
1 There were 7 patients (as described in Table 7) who did not receive treatment and were counted as failures in the analysis. | |||
2 Patients who died, used non-study antibacterial therapy, or had an unplanned surgical intervention 72 hours after the start of therapy were classified as Clinical Failures. | |||
3 The 95% CI is computed using the Miettinen and Nurminen approach, stratified by baseline fever status. |
Table 10 shows outcomes in patients with an identified baseline pathogen, using pooled data from Trials 1 and 2 in the microbiological ITT (microITT) population. The outcomes shown in the table are clinical response rates at 48 to 72 hours and clinical success rates at follow-up (Day 26 to 30), as defined above.
All DALVANCE dosing regimens in Trials 1 and 2 consisted of two doses. | ||||||
1 There were 2 patients in the DALVANCE arm with methicillin-susceptible S. aureus at baseline who did not receive treatment and were counted as non-responders/failures. | ||||||
2 Early Responders are patients who had no increase from baseline in lesion area 48 to 72 hours after initiation of therapy, and had a temperature consistently at or below 37.6° C upon repeated measurement. | ||||||
Early Clinical Response at 48-72 hours | ||||||
| Early Responder2 | ≥ 20% reduction in lesion size | Clinical Success at Day 26 to 30 | |||
Pathogen | DALVANCE n/N (%) | Comparator n/N (%) | DALVANCE n/N (%) | Comparator n/N (%) | DALVANCE n/N (%) | Comparator n/N (%) |
Staphylococcus aureus Methicillin-susceptible Methicillin-resistant | 206/257 (80.2) 134/167 (80.2) 72/90 (80.0) | 219/256 (85.5) 163/189 (86.2) 56/67 (83.6) | 239/257 (93.0) 156/167 (93.4) 83/90 (92.2) | 232/256 (90.6) 173/189 (91.5) 59/67 (88.1) | 217/257 (84.4) 142/167 (85.0) 75/90 (83.3) | 229/256 (89.5) 171/189 (90.5) 57/67 (85.1) |
Streptococcus agalactiae | 6/12 (50.0) | 11/14 (78.6) | 10/12 (83.3) | 10/14 (71.4) | 10/12 (83.3) | 11/14 (78.6) |
Streptococcus pyogenes | 28/37 (75.7) | 24/36 (66.7) | 32/37 (86.5) | 27/36 (75.0) | 33/37 (89.2) | 32/36 (88.9) |
Streptococcus anginosus group | 18/22 (81.8) | 23/ 25 (92.0) | 21/22 (95.5) | 25/25 (100.0) | 21/22 (95.5) | 23/25 (92.0) |
Enterococcus faecalis | 8/12 (66.7) | 10/13 (76.9) | 12/12 (100.0) | 12/13 (92.3) | 12/12 (100.0) | 11/13 (84.6) |
15 References
- Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antibiotic Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Tenth Edition. CLSI document M07-A10. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
- CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement. CLSI document M100-S25 Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
16 How Supplied/Storage And Handling
DALVANCE (dalbavancin) for injection is supplied in the following packaging configuration:
- 500 mg/vial: package of 1 (NDC 57970-100-01)
Unreconstituted DALVANCE (dalbavancin) for injection should be stored at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].
17 Patient Counseling Information
Patients should be advised that allergic reactions, including serious allergic reactions, could occur, and that serious allergic reactions require immediate treatment. Patients should inform their healthcare provider about any previous hypersensitivity reactions to DALVANCE, or other glycopeptides.
Patients should be counseled that antibacterial drugs including DALVANCE should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When DALVANCE 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 treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by DALVANCE and other antibacterial drugs in the future.
Patients should be advised that diarrhea is a common problem caused by antibacterial drugs and usually resolves when the drug is discontinued. Sometimes, frequent watery or bloody diarrhea may occur and may be a sign of a more serious intestinal infection. If severe watery or bloody diarrhea develops, patients should contact their healthcare provider.
Manufactured for: Durata Therapeutics U.S. Limited
Parsippany, NJ 07054
US Patent Numbers: Available online at http://www.duratatherapeutics.com/products/product-patents
DALVANCE is a registered trademark of Durata Therapeutics Holding C.V.
* Please review the disclaimer below.