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 )
1.1Acute 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).
Contraindications
Dalbavancin for injection is contraindicated in patients with known hypersensitivity to dalbavancin. Known hypersensitivity to dalbavancin ( 4 )
Warnings and precautions
Serious hypersensitivity (anaphylactic) and skin reactions have been reported in patients treated with dalbavancin for injection. If an allergic reaction occurs, discontinue treatment with dalbavancin for injection and institute appropriate therapy for the allergic reaction. Carefully monitor patients with known hypersensitivity to glycopeptides. ( 5.1 ) Rapid intravenous infusion of dalbavancin for injection 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 dalbavancin for injection 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 dalbavancin for injection. Evaluate if diarrhea occurs. ( 5.4 )
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Serious hypersensitivity (anaphylactic) and skin reactions have been reported in patients treated with dalbavancin for injection. If an allergic reaction to dalbavancin for injection occurs, discontinue treatment with dalbavancin for injection and institute appropriate therapy for the allergic reaction. Before using dalbavancin for injection, 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 dalbavancin for injection in patients with a history of glycopeptide allergy [see Patient Counseling Information ( 17 )] .
5.2Infusion-Related Reactions Dalbavancin
for injection 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 dalbavancin for injection 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 dalbavancin for injection 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 dalbavancin for injection 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 dalbavancin for injection, 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.
5.5Development of Drug-Resistant Bacteria
Prescribing dalbavancin for injection 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.
Interactions
7.1Drug-Laboratory Test Interactions
Drug-laboratory test interactions have not been reported. Dalbavancin for injection at therapeutic concentrations does not artificially prolong prothrombin time (PT) or activated partial thromboplastin time (aPTT).
7.2Drug-Drug Interactions
No clinical drug-drug interaction studies have been conducted with dalbavancin for injection. There is minimal potential for drug-drug interactions between dalbavancin for injection and cytochrome P450 (CYP450) substrates, inhibitors, or inducers [see Clinical Pharmacology ( 12.3 )] .
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
There are no adequate and well-controlled studies with dalbavancin for injection 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).
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 Long Grove Pharmaceuticals, LLC at 1-855-642-2594 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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 (N = 1,778) Comparator * (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 of dalbavancin for injection, 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 of dalbavancin for injection and 78 patients treated with another dalbavancin dosing regimen group) 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
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Composition
Active ingredients
DALBAVANCIN HYDROCHLORIDE EQ 500MG BASE/VIAL
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
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