Dalbavancin

FDA Drug Information • Also known as: Dalbavancin, Dalvance

Brand Names: Dalbavancin, Dalvance
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION 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

What Is Dalbavancin Used For?

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.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION 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...

Side Effects (Adverse Reactions)

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 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...

Drug Interactions

7 DRUG INTERACTIONS 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 )] .

Contraindications

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

Pregnancy and Breastfeeding

8.1 Pregnancy 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).

Overdosage

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 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 )].

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 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 )].

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.