Dalbavancin

DALVANCE (dalbavancin) for injection is a lipoglycopeptide antibacterial synthesized from a fermentation product of Nonomuraea species. Dalbavancin is a mixture of five closely related active homologs (A 0 , A 1 , B 0 , B 1 , and B 2 ); the component B 0 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 (R 1 ) structure and/or the presence of an additional methyl group (R 2 ) on the terminal amino group (shown in the Figure 1 and Table 3 below). Figure 1. Dalbavancin Structural Formula Table 3. Substitution Patterns for Dalbavancin API Homologs Dalbavancin R 1 R 2 Molecular Formula Molecular Weight * A 0 CH(CH 3 ) 2 H C 87 H 98 N 10 O 28 Cl 2 · 1.6 HCl 1,802.7 A 1 CH 2 CH 2 CH 3 H C 87 H 98 N 10 O 28 Cl 2 · 1.6 HCl 1,802.7 B 0 CH 2 CH(CH 3 ) 2 H C 88 H 100 N 10 O 28 Cl 2 · 1.6 HCl 1,816.7 B 1 CH 2 CH 2 CH 2 CH 3 H C 88 H 100 N 10 O 28 Cl 2 · 1.6 HCl 1,816.7 B 2 CH 2 CH(CH 3 ) 2 CH 3 C 89 H 102 N 10 O 28 Cl 2 · 1.6 HCl 1,830.7 *Anhydrous free base The B 0 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 (125 mg) and mannitol (125 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 ( 2.4 ) , How Supplied/Storage and Handling ( 16 ) ] . Figure 1. Dalbavancin Structural Formula

1 INDICATION AND USAGE DALVANCE is a lipoglycopeptide antibacterial indicated for the treatment of adult and pediatric patients with acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible strains of Gram-positive microorganisms. ( 1.1 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of DALVANCE and other antibacterial drugs, DALVANCE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. ( 1.2 ) 1.1 Acute Bacterial Skin and Skin Structure Infections DALVANCE ® is indicated for the treatment of adult and pediatric patients with acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible strains of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes , Streptococcus agalactiae , Streptococcus dysgalactiae , Streptococcus anginosus group (including S. anginosus , S. intermedius , S . constellatus ) and Enterococcus faecalis (vancomycin susceptible isolates). 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 or prevent 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.

DALVANCE (dalbavancin) for injection is supplied as a white/off-white to pale yellow sterile lyophilized powder in a single-dose glass vial containing dalbavancin hydrochloride equivalent to 500 mg dalbavancin: Package of 1 individual vial (500 mg/vial) in carton: (NDC 57970-100-01) DALVANCE (dalbavancin) for injection should be stored at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Storage of the reconstituted and diluted solutions of DALVANCE are described elsewhere in the prescribing information [see Dosage and Administration ( 2.4 )].

Dosage in Adult Patients ( 2.1 , 2.3 ): Estimated Creatinine Clearance ( C L cr) Single Dose Regimen Two-D ose Regimen 30 mL/min and above or on regular hemodialysis 1,500 mg 1,000 mg followed one week later by 500 mg Less than 30 mL/min and not on regular hemodialysis 1,125 mg 750 mg followed one week later by 375 mg Administer by intravenous infusion over 30 minutes ( 2.1 , 2.4 ) See Full Prescribing Information for instructions on reconstitution of lyophilized powder and preparation of injection ( 2.4 ). Dosage in Pediatric Patients with CLcr 30 mL/min/1.73m 2 and above ( 2.2 ) Age Range Dosage (Single Dose Regimen) Birth to less than 6 years 22.5 mg/kg (maximum of 1,500 mg) 6 to less than 18 years 18 mg/kg (maximum of 1,500 mg) Dosage adjustment in pediatric patients with CLcr less than 30 mL/min has not been studied. 2.1 Recommended Dos ag e Regimen in Adult Patients with CLcr 30 mL/min and Above The recommended dosage regimen of DALVANCE in adult patients with CLcr 30 mL/min and above is 1,500 mg, administered either as a single dose regimen, or as a two-dose regimen of DALVANCE 1,000 mg followed one week later by 500 mg. Administer DALVANCE over 30 minutes by intravenous infusion. For adult patients with CLcr less than 30 mL/min, dosage adjustment is required [see Dosage and Administration ( 2.3 ) and Clinical Pharmacology ( 12.3 ) ] . 2.2 Recommended Dosage Regimen in Pediatric Patients with CLcr 30 mL/min/ 1.73m 2 and Abov e The recommended dosage regimen of DALVANCE in pediatric patients with CLcr 30 mL/min/1.73m 2 and above is a single dose regimen based on the age and weight of the pediatric patient ( Table 1 ). Administer DALVANCE over 30 minutes by intravenous infusion. There is insufficient information to recommend dosage adjustment for pediatric patients younger than 18 years with CLcr less than 30 mL/min/1.73m 2 [see Use in Specific Populations ( 8.4 ) and Clinical Pharmacology ( 12.3 )] . Table 1. Dosage of DALVANCE in Pediatric Patients with CLcr* 30 mL/min/1.73m2 and above Age Range Dosage (Single Dose Regimen) Birth to less than 6 years 22.5 mg/kg (maximum 1,500 mg) 6 to less than 18 years 18 mg/kg (maximum 1,500 mg) *Estimate CLcr or glomerular filtration rate (GFR) using an age-appropriate equation accepted for pediatric patients (birth to less than 18 years old) to define renal function impairment. 2.3 Dosage Adjustments in Adult Patients with CLcr less than 30 mL/min In adult patients with renal impairment whose known CLcr is less than 30 mL/min and who are not receiving regularly scheduled hemodialysis, the recommended dosage regimen of DALVANCE is 1,125 mg, administered either as a single dose regimen, or as a two-dose regimen of DALVANCE 750 mg followed one week later by 375 mg. No dosage adjustment is recommended for adult patients receiving regularly scheduled hemodialysis, and DALVANCE can be administered without regard to the timing of hemodialysis [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] . 2.4 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. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 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°C to 8°C (36°F to 46°F), or at controlled room temperature 20°C to 25°C (68°F to 77°F). Do not freeze. Dilution: Adult Patients: Aseptically transfer the required dose of reconstituted DALVANCE 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. Pediatric Patients: For pediatric patients, the dose of DALVANCE will vary according to the age and weight of the child up to a maximum of 1,500 mg [see Dosage and Administration ( 2.2 )] . Aseptically transfer the required dose of reconstituted DALVANCE solution, based on the child’s weight, 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°C to 8°C (36°F to 46°F) or at a controlled room temperature of 20°C to 25°C (68°F 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, administer DALVANCE 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.

DALVANCE is contraindicated in patients with known hypersensitivity to dalbavancin. Known hypersensitivity to dalbavancin ( 4 )

Serious hypersensitivity (anaphylactic) and skin reactions have been reported in patients treated with DALVANCE. If an allergic reaction occurs, discontinue treatment with DALVANCE and institute appropriate therapy for the allergic reaction. Carefully monitor patients with known hypersensitivity to glycopeptides. ( 5.1 ) Rapid intravenous infusion of DALVANCE can cause flushing of the upper body, urticaria, pruritus, rash, and/or back pain. Stopping or slowing the infusion may result in cessation of these reactions. ( 5.2 ) Alanine Aminotransferase (ALT) elevations with DALVANCE treatment were reported in clinical trials. ( 5.3 , 6.1 ) Clostridioides difficile -associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including DALVANCE. Evaluate if diarrhea occurs. ( 5.4 ) 5.1 Hypersensitivity Reactions Serious hypersensitivity (anaphylactic) and skin reactions have been reported in patients treated with DALVANCE. If an allergic reaction to DALVANCE occurs, discontinue treatment with DALVANCE and institute appropriate therapy for the allergic reaction. Before using DALVANCE, inquire carefully about previous hypersensitivity reactions to other glycopeptides. Due to the possibility of cross-sensitivity, carefully monitor for signs of hypersensitivity during treatment with DALVANCE 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 flushing of the upper body, urticaria, pruritus, rash, and/or back pain. 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 Clostridioides difficile - Associated Diarrhea Clostridioides 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 or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Allergic Reactions Advise patients that allergic reactions, including serious allergic reactions, could occur with DALVANCE, and that serious allergic reactions require immediate treatment. Patients should inform their healthcare provider about any previous hypersensitivity reactions to DALVANCE, or other glycopeptides [see Warnings and Precautions ( 5.1 )] . Diarrhea Advise patients that diarrhea is a common problem caused by antibacterial drugs, including DALVANCE, 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 [see Warnings and Precautions ( 5.4 )] . Development of Drug-Resistant Bacteria 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 the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by DALVANCE or other antibacterial drugs in the future [see Warnings and Precautions ( 5.5 )] . Distributed by: AbbVie Inc. North Chicago, IL 60064 DALVANCE and its design are trademarks of Allergan Pharmaceuticals International Limited, an AbbVie company. © 2025 AbbVie. All rights reserved. PAA234914

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 C linical P harmacology ( 12.3 )] .

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).

Carcinogenesis Long-term studies in animals to determine the carcinogenic potential of dalbavancin have not been conducted. Mutagenesis 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. Impairment of Fertility 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 .

Risk Summary There are no adequate and well-controlled studies with DALVANCE use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse developmental outcomes. No treatment-related malformations or embryo-fetal toxicity were observed in pregnant rats or rabbits at clinically relevant exposures of dalbavancin. Treatment of pregnant rats with dalbavancin at 3.5 times the human dose on an exposure basis during early embryonic development and from implantation to the end of lactation resulted in delayed fetal maturation and increased fetal loss, respectively [ see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data No evidence of embryo or fetal toxicity was found in the rat or rabbit at a dose of 15 mg/kg/day (1.2 and 0.7 times the human dose on an exposure basis, respectively). Delayed fetal maturation was observed in the rat at a dose of 45 mg/kg/day (3.5 times the human dose on an exposure basis). In a rat prenatal and postnatal development study, increased embryo lethality and increased offspring deaths during the first week post-partum were observed at a dose of 45 mg/kg/day (3.5 times the human dose on an exposure basis).

The safety and effectiveness of DALVANCE for the treatment of ABSSSI has been established in pediatric patients aged birth to less than 18 years. Use of DALVANCE for this indication is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients aged birth to less than 18 years [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies (14.1)] . There is insufficient information to recommend dosage adjustment for pediatric patients with ABSSSI and CLcr less than 30 mL/min/1.73m 2 [see Dosage and Administration ( 2.2 )].

8. 5 Geriatric Use Of the 2,473 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.

The following clinically significant adverse reactions are also discussed elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Infusion Related Reactions [see Warnings and Precautions ( 5.2 )] Hepatic Effects [see Warnings and Precautions ( 5.3 )] Clostridioides difficile -associated Diarrhea [see Warnings and Precautions ( 5.4 )] The most common adverse reactions occurring in >4% of adult patients treated with DALVANCE were nausea, headache, and diarrhea. The most common adverse reaction that occurred in >1% of pediatric patients was pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. Clinical Trials Experience in Adult Patients Adverse reactions were evaluated for 2,473 patients treated with DALVANCE: 1,778 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. 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%). Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 121/2,473 (4.9%) of patients treated with any regimen of DALVANCE. In the Phase 2/3 trials comparing DALVANCE to comparator, serious adverse reactions occurred in 109/1,778 (6.1%) of patients in the DALVANCE group and 80/1,224 (6.5%) of patients in the comparator group. In a Phase 3 trial comparing DALVANCE single and two-dose regimens, serious adverse reactions occurred in 7/349 (2.0%) of patients in the DALVANCE single dose group and 5/346 (1.4%) of patients in the DALVANCE two-dose group. DALVANCE was discontinued due to an adverse reaction in 64/2,473 (2.6%) patients treated with any regimen of DALVANCE. In the Phase 2/3 trials comparing DALVANCE to comparator, DALVANCE was discontinued due to an adverse reaction in 53/1,778 (3.0%) of patients in the DALVANCE group and 35/1,224 (2.9%) of patients in the comparator group. In a Phase 3 trial comparing DALVANCE single and two-dose regimens, DALVANCE was discontinued due to an adverse reaction in 6/349 (1.7%) of patients in the DALVANCE single dose group and 5/346 (1.4%) of patients in the DALVANCE two-dose group. Most Common Adverse Reactions The most common adverse reactions in patients treated with DALVANCE in Phase 2/3 trials were nausea (5.5%), headache (4.7%), and diarrhea (4.4%). The median duration of adverse reactions was 3.0 days in patients treated with DALVANCE. In the Phase 2/3 trials comparing DALVANCE to comparator, the median duration of adverse reactions was 3.0 days for patients in the DALVANCE group and 4.0 days in patients in the comparator group. In a Phase 3 trial comparing DALVANCE single and two-dose regimens, the median duration of adverse reactions was 3.0 days for patients in the DALVANCE single and two-dose group. Table 2 lists selected adverse reactions occurring in 2% or more of patients treated with DALVANCE in Phase 2/3 clinical trials. Table 2. Selected Adverse Reactions Occurring in ≥ 2% of Patients Receiving DALVANCE in Phase 2/3 Trials (Number (%) of Patients) Adverse Reactions DALVANCE Comparator* (N = 1 , 778) (N = 1 , 224) Nausea 98 (5.5) 78 (6.4) Diarrhea 79 (4.4) 72 (5.9) Headache 83 (4.7) 59 (4.8) Vomiting 50 (2.8) 37 (3) Rash 48 (2.7) 30 (2.4) Pruritus 38 (2.1) 41 (3.3) * Comparators included linezolid, cefazolin, cephalexin, and vancomycin. In the Phase 3 trial comparing the single and two-dose regimen of DALVANCE, the adverse reaction that occurred in 2% or more of patients treated with DALVANCE was nausea (3.4% in the DALVANCE single dose group and 2% in the DALVANCE two-dose group). The following selected adverse reactions were reported in DALVANCE treated patients at a rate of less than 2% in these clinical trials: Blood and lymphatic system disorders : anemia, hemorrhagic anemia, leucopenia, neutropenia, thrombocytopenia, petechiae, eosinophilia, thrombocytosis Gastrointestinal d isorders : gastrointestinal hemorrhage, melena, hematochezia, abdominal pain General d isorders and administration site conditions : infusion-related reactions Hepatobiliary disorders : hepatotoxicity Immune system disorders : anaphylactic reaction Infections and infestations : Clostridioides difficile colitis, oral candidiasis, vulvovaginal mycotic infection Investigations : hepatic transaminases increased, blood alkaline phosphatase increased, international normalized ratio increased, blood lactate dehydrogenase increased, gamma-glutamyl transferase increased Metaboli sm and nutrition disorders : hypoglycemia Nervous s ystem disorders : dizziness Respiratory, thoracic and media s tinal disorders : bronchospasm Skin and s ubcutaneous t issue d isorders : rash, pruritus, urticaria Vascular disorders : flushing, phlebitis, wound hemorrhage, spontaneous hematoma Alanine Aminotransferase (ALT) Elevations Among patients with normal baseline ALT levels treated with DALVANCE 17 (0.8%) had post baseline ALT elevations greater than 3 times the upper limit of normal (ULN) including five subjects with post-baseline ALT values greater than 10 times ULN. Among patients with normal baseline ALT levels treated with non-DALVANCE comparators 2 (0.2%) had post-baseline ALT elevations greater than 3 times the upper limit of normal. Fifteen of the 17 patients treated with DALVANCE and one comparator patient had underlying conditions which could affect liver enzymes, including chronic viral hepatitis, history of alcohol abuse and metabolic syndrome. In addition, one DALVANCE-treated subject in a Phase 1 trial had post-baseline ALT elevations greater than 20 times ULN. ALT elevations were reversible in all subjects with follow-up assessments. No comparator-treated subject with normal baseline transaminases had post-baseline ALT elevation greater than 10 times ULN. Clinical Trials Experience in Pediatric Patients Adverse reactions were evaluated in one Phase 3 pediatric clinical trial which included 161 pediatric patients from birth to less than 18 years of age with ABSSSI treated with DALVANCE (83 patients treated with a single dose of DALVANCE and 78 patients treated with a two-dose regimen of DALVANCE) and 30 patients treated with comparator agents for a treatment period up to 14 days. The median age of pediatric patients treated with DALVANCE was 9 years, ranging from birth to <18 years. The majority of patients were male (62.3%) and White (89.0%). The safety findings of DALVANCE in pediatric patients were similar to those observed in adults. Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions (SARs) occurred in 3/161 (1.9%) of patients treated with DALVANCE, all in the single-dose arm. There were no adverse reactions leading to DALVANCE discontinuation. Most Common Adverse Reactions Most common adverse reaction occurring in more than 1% of pediatric patients 2/161 (1.2%) was pyrexia. Other Adverse Reactions The following selected adverse reactions were reported in DALVANCE-treated patients at a rate of less than 1% in this pediatric clinical trial: Gastrointestinal disorders : diarrhea Nervous system disorders : dizziness Skin and subcutaneous tissue disorders : pruritus 6.2 Post Marketing Experience The following adverse reaction has been identified during post-approval use of dalbavancin. Because the reaction is reported voluntarily from a population of uncertain size, it is not possible to reliably estimate the frequency or establish a causal relationship to drug exposure. General disorders and administration site conditions: Back pain as an infusion-related reaction [See Warnings and Precautions ( 5.2 )].

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 4,500 mg over a period of up to 8 weeks (not an approved dosing regimen), 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 )].