1 INDICATION AND USAGE Dalbavancin for injection 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 dalbavancin for injection and other antibacterial drugs, dalbavancin for injection 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 Dalbavancin for injection 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 dalbavancin for injection and other antibacterial agents, dalbavancin for injection 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.

6 ADVERSE REACTIONS 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 dalbavancin for injection 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 Fresenius Kabi USA, LLC at 1-800-551-7176 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 dalbavancin for injection 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 dalbavancin for injection: 1,778 patients were treated with dalbavancin for injection in seven Phase 2/3 trials comparing dalbavancin for injection to comparator antibacterial drugs and 695 patients were treated with dalbavancin for injection in one Phase 3 trial comparing dalbavancin for injection single dose and another dalbavancin dosing regimen.

The median age of patients treated with dalbavancin for injection was 48 years, ranging between 16 and 93 years.

Patients treated with dalbavancin for injection 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 dalbavancin for injection.

In the Phase 2/3 trials comparing dalbavancin for injection to comparator, serious adverse reactions occurred in 109/1,778 (6.1%) of patients in the dalbavancin for injection group and 80/1,224 (6.5%) of patients in the comparator group.

In a Phase 3 trial comparing dalbavancin for injection single dose and another dalbavancin dosing regimen, serious adverse reactions occurred in 7/349 (2.0%) of patients in the dalbavancin for injection single dose group and 5/346 (1.4%) of patients in another dalbavancin dosing regimen group.

Dalbavancin for injection was discontinued due to an adverse reaction in 64/2,473 (2.6%) patients treated with any regimen of dalbavancin for injection.

In the Phase 2/3 trials comparing dalbavancin for injection to comparator, dalbavancin for injection was discontinued due to an adverse reaction in 53/1,778 (3.0%) of patients in the dalbavancin for injection group and 35/1,224 (2.9%) of patients in the comparator group.

In a Phase 3 trial comparing dalbavancin for injection single dose and another dalbavancin dosing regimen, dalbavancin for injection was discontinued due to an adverse reaction in 6/349 (1.7%) of patients in the dalbavancin for injection single dose group and 5/346 (1.4%) of patients in another dalbavancin dosing regimen group.

Most Common Adverse Reactions The most common adverse reactions in patients treated with dalbavancin for injection 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 dalbavancin for injection.

In the Phase 2/3 trials comparing dalbavancin for injection to comparator, the median duration of adverse reactions was 3.0 days for patients in the dalbavancin for injection group and 4.0 days in patients in the comparator group.

In a Phase 3 trial comparing dalbavancin for injection single dose and another dalbavancin dosing regimen, the median duration of adverse reactions was 3.0 days for patients in the dalbavancin for injection single dose and another dalbavancin dosing regimen group.

Table 2 lists selected adverse reactions occurring in 2% or more of patients treated with dalbavancin for injection in Phase 2/3 clinical trials.

Table 2.

Selected Adverse Reactions Occurring in ≥ 2% of Patients Receiving Dalbavancin for Injection in Phase 2/3 Trials (Number (%) of Patients) * Comparators included linezolid, cefazolin, cephalexin, and vancomycin.

Adverse Reactions Dalbavancin for Injection 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) In the Phase 3 trial comparing the single dose and another dalbavancin dosing regimen, the adverse reaction that occurred in 2% or more of patients treated with dalbavancin for injection was nausea (3.4% in the dalbavancin for injection single dose group and 2% in another dalbavancin dosing regimen group).

The following selected adverse reactions were reported in dalbavancin for injection 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 disorders : gastrointestinal hemorrhage, melena, hematochezia, abdominal pain General disorders 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 Metabolism and nutrition disorders : hypoglycemia Nervous system disorders : dizziness Respiratory, thoracic and mediastinal disorders : bronchospasm Skin and subcutaneous tissue disorders : rash, pruritus, urticaria Vascular disorders : flushing, phlebitis, wound hemorrhage, spontaneous hematoma Alanine Aminotransferase (ALT) Elevations Among patients with normal baseline ALT levels treated with dalbavancin for injection 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-dalbavancin for injection 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 dalbavancin for injection 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 dalbavancin for injection-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 dalbavancin for injection (83 patients treated with a single dose and 78 patients treated with another dalbavancin dosing regimen) and 30 patients treated with comparator agents for a treatment period up to 14 days.

The median age of pediatric patients treated with dalbavancin for injection 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 dalbavancin for injection 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 dalbavancin for injection, all in the single-dose arm.

There were no adverse reactions leading to dalbavancin for injection 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 dalbavancin for injection-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 )] .