Dalbavancin Zentiva: Uses, Dosage & Side Effects

What Is Dalbavancin Zentiva and What Is It Used For?

Dalbavancin Zentiva contains the active substance dalbavancin, a semisynthetic lipoglycopeptide antibiotic derived from the naturally occurring glycopeptide A-40926, which is produced by the actinomycete Nonomuraea species. Lipoglycopeptides represent a modern evolution of the glycopeptide antibiotic class, which includes vancomycin and teicoplanin—drugs that have been cornerstones of Gram-positive infection therapy for decades. What distinguishes dalbavancin from its predecessors is a lipophilic (fat-soluble) side chain attached to the glycopeptide core, which dramatically enhances its antibacterial potency, increases its binding affinity to target sites on the bacterial cell wall, and extends its duration of action in the body.

The mechanism of action of dalbavancin centers on the inhibition of bacterial cell wall synthesis. Like all glycopeptides, dalbavancin binds with high affinity to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of the stem pentapeptide in nascent peptidoglycan, the structural polymer that provides rigidity and integrity to the bacterial cell wall. By occupying this critical binding site, dalbavancin physically blocks the transglycosylation and transpeptidation enzymatic steps that are essential for cross-linking peptidoglycan strands. Without proper cross-linking, the bacterial cell wall becomes structurally compromised, leading to osmotic instability and ultimately bacterial cell death. The lipophilic side chain of dalbavancin provides an additional anchoring mechanism by inserting into the bacterial cell membrane, which increases the local concentration of the antibiotic at its site of action and enhances its bactericidal activity compared to vancomycin.

Dalbavancin exhibits concentration-dependent bactericidal activity against a broad range of clinically relevant Gram-positive organisms. Its spectrum of activity includes Staphylococcus aureus (both methicillin-susceptible [MSSA] and methicillin-resistant [MRSA] strains), coagulase-negative staphylococci (including S. epidermidis and S. hominis), Streptococcus pyogenes (group A streptococcus), Streptococcus agalactiae (group B streptococcus), the Streptococcus anginosus group, and certain Enterococcus species (notably E. faecalis, though not vancomycin-resistant enterococci [VRE]). The minimum inhibitory concentrations (MICs) of dalbavancin against these pathogens are typically very low, often 4–16 fold lower than those of vancomycin, reflecting the enhanced potency conferred by its structural modifications.

The defining pharmacokinetic characteristic of dalbavancin is its exceptionally long terminal elimination half-life of approximately 346 hours (roughly 14.4 days). This prolonged half-life results from a combination of factors: high plasma protein binding (approximately 93%, primarily to albumin), slow tissue distribution with good penetration into skin and skin structures (the primary sites of ABSSSI), and limited metabolism with dual renal and fecal excretion pathways. This pharmacokinetic profile allows for infrequent dosing—either a single 1,500 mg intravenous infusion or a two-dose regimen of 1,000 mg on day 1 followed by 500 mg on day 8. Both regimens maintain antibacterial concentrations above the MIC for susceptible organisms for approximately 14 days, providing a full course of treatment with minimal intravenous administrations.

Dalbavancin is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults. ABSSSI is a regulatory term encompassing three major clinical presentations: cellulitis/erysipelas (spreading infection of the skin and subcutaneous tissue), wound infections (including surgical site infections and traumatic wound infections), and major cutaneous abscesses (defined as having at least 75 cm² of surrounding erythema, induration, or edema). These infections are predominantly caused by Gram-positive organisms, with S. aureus (including MRSA) being the most common pathogen, followed by beta-hemolytic streptococci.

The clinical efficacy of dalbavancin in ABSSSI was established in two pivotal phase III randomized, double-blind, non-inferiority clinical trials:

• DISCOVER 1 and DISCOVER 2: These two identically designed trials enrolled a combined total of 1,312 adults with ABSSSI. Patients were randomized to receive either dalbavancin (a two-dose regimen of 1,000 mg on day 1 followed by 500 mg on day 8) or vancomycin (1 g intravenously every 12 hours for at least 3 days, with an option to switch to oral linezolid to complete 10–14 days of therapy). The primary endpoint was early clinical response at 48–72 hours, defined as cessation of spread and reduction of lesion size by at least 20%. In both trials, dalbavancin demonstrated non-inferiority to the vancomycin/linezolid regimen, with clinical success rates of approximately 79–83% in the dalbavancin group compared to 78–82% in the comparator group.
• DUR001-303 (Single-Dose Study): This additional phase III trial compared a single 1,500 mg dose of dalbavancin with the two-dose regimen (1,000 mg + 500 mg) in 698 patients with ABSSSI. The single-dose regimen was shown to be non-inferior to the two-dose regimen at the early clinical response endpoint. This study provided the clinical evidence supporting the single-dose option, further simplifying the treatment course.

Dalbavancin was first approved by the U.S. Food and Drug Administration (FDA) in May 2014 under the brand name Dalvance, and subsequently by the European Medicines Agency (EMA) in February 2015 under the brand name Xydalba. The Zentiva formulation represents a generic/biosimilar equivalent that has been approved through regulatory pathways demonstrating pharmaceutical equivalence with the originator product. The availability of dalbavancin has been particularly welcomed in clinical settings where reducing the duration of intravenous therapy is a priority, such as in outpatient parenteral antibiotic therapy (OPAT) programs, where patients can receive a single infusion and be discharged without the need for ongoing intravenous access.

What Should You Know Before Taking Dalbavancin Zentiva?

Contraindications

The primary contraindication to the use of Dalbavancin Zentiva is hypersensitivity (allergy) to the active substance dalbavancin or to any of the excipients in the formulation. The excipients include mannitol, lactose monohydrate, hydrochloric acid, and sodium hydroxide (used for pH adjustment). If you have a known allergy to any of these substances, you must not receive Dalbavancin Zentiva.

There is a risk of cross-sensitivity between dalbavancin and other glycopeptide antibiotics, including vancomycin and teicoplanin. Patients who have experienced hypersensitivity reactions to vancomycin or teicoplanin should inform their healthcare provider before receiving dalbavancin. While cross-reactivity is not universal, caution is warranted, and the decision to use dalbavancin in patients with a history of glycopeptide allergy should be made on a case-by-case basis with appropriate monitoring. Serious hypersensitivity reactions, including anaphylaxis, have been reported with glycopeptide antibiotics as a class.

Warnings and Precautions

Before receiving Dalbavancin Zentiva, discuss the following with your healthcare provider:

• Clostridioides difficile-associated diarrhea (CDAD): As with nearly all antibiotics, dalbavancin can disrupt the normal intestinal flora, potentially leading to overgrowth of Clostridioides difficile (formerly Clostridium difficile) and associated diarrhea or colitis. CDAD has been reported with dalbavancin use. Symptoms can range from mild diarrhea to severe, life-threatening pseudomembranous colitis. If you develop significant diarrhea during or after treatment with dalbavancin, inform your doctor immediately. CDAD should be considered in all patients presenting with diarrhea following antibiotic use.
• Superinfection: The use of any antibiotic may lead to the emergence of resistant organisms or superinfection with non-susceptible pathogens, including fungi. If a superinfection develops during therapy, your doctor will take appropriate measures, which may include alternative antibiotic treatment.
• Hepatic effects: Elevations in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal have been observed in some patients treated with dalbavancin in clinical trials. Patients with pre-existing liver disease or those receiving concomitant hepatotoxic medications may be at increased risk. Liver function should be monitored in patients who develop signs or symptoms of hepatic dysfunction during treatment.
• Renal impairment: Dalbavancin is partially eliminated through the kidneys. In patients with severe renal impairment (creatinine clearance less than 30 mL/min) who are not receiving regular hemodialysis, a dose reduction is recommended. No dose adjustment is needed for patients with mild to moderate renal impairment or for those on regular hemodialysis (see Dosage section).
• Limitations of use: Dalbavancin is active only against Gram-positive bacteria. It has no clinically meaningful activity against Gram-negative organisms or atypical bacteria. If mixed or Gram-negative infections are suspected or confirmed, additional antibiotics with appropriate Gram-negative coverage must be prescribed.

Children and Adolescents

The safety and efficacy of Dalbavancin Zentiva have not been established in children and adolescents under 18 years of age. Current clinical trial data are insufficient to recommend its use in the pediatric population. Pediatric pharmacokinetic and safety studies are ongoing. Healthcare providers should consider age-appropriate alternative antibiotics for ABSSSI in children and adolescents, following established guidelines from the Infectious Diseases Society of America (IDSA) and the European Society for Paediatric Infectious Diseases (ESPID).

Pregnancy and Breastfeeding

The safety of Dalbavancin Zentiva during pregnancy has not been adequately established in humans. Animal reproductive toxicity studies have shown evidence of developmental toxicity (increased embryolethality, increased fetal malformations, and decreased fetal weights) at doses producing maternal exposures approximately 3.5 times the human exposure at the clinical dose. While these findings in animals do not necessarily predict effects in humans, as a precaution, Dalbavancin Zentiva should not be used during pregnancy unless the potential benefit clearly justifies the potential risk to the fetus. Women of childbearing potential should use effective contraception during treatment.

It is not known whether dalbavancin or its metabolites are excreted in human breast milk. Dalbavancin was detected in the milk of lactating rats. Given the long half-life of dalbavancin (approximately 14 days), the potential for exposure of the breastfed infant is prolonged. A risk to the breastfed infant cannot be excluded. The decision to discontinue breastfeeding or to withhold dalbavancin treatment should be made in consultation with your healthcare provider, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.

Driving and Operating Machinery

No studies on the effects of dalbavancin on the ability to drive and use machines have been performed. Based on the reported adverse reactions (which can include dizziness and headache), dalbavancin may have a minor influence on the ability to drive and operate machinery. If you experience dizziness or other neurological effects after receiving dalbavancin, refrain from driving or operating heavy machinery until these symptoms have resolved.

Important Information About Ingredients

Dalbavancin Zentiva contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not receive this medicine. Each 500 mg vial of Dalbavancin Zentiva also contains less than 1 mmol (23 mg) of sodium per dose, meaning it is essentially sodium-free. This is relevant for patients on a sodium-restricted diet.

How Does Dalbavancin Zentiva Interact with Other Drugs?

Dalbavancin has a relatively favorable drug interaction profile. In vitro studies have demonstrated that dalbavancin does not significantly inhibit or induce the major cytochrome P450 (CYP) enzyme isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). This means that dalbavancin is unlikely to affect the plasma concentrations of medications metabolized through these common hepatic enzyme pathways. Dalbavancin is not a substrate for CYP enzymes and is minimally metabolized, with the primary route of elimination being through a combination of renal excretion and fecal elimination of unchanged drug and a minor hydroxy-metabolite.

Formal drug-drug interaction studies have been limited. However, population pharmacokinetic analyses from the clinical trial program have not identified clinically meaningful effects of commonly co-administered medications on dalbavancin pharmacokinetics. The high protein binding of dalbavancin (approximately 93%) is primarily to albumin, and in vitro studies suggest that dalbavancin does not significantly displace other highly protein-bound drugs from their binding sites at clinically relevant concentrations.

Despite the favorable interaction profile, healthcare providers should exercise appropriate clinical judgment when administering dalbavancin alongside other medications. The following table summarizes the current understanding of dalbavancin interactions with commonly co-administered drug classes:

It is important to note that while no formal pharmacokinetic interactions have been demonstrated, dalbavancin should be used with caution in patients receiving other medications known to prolong the QTc interval, as isolated cases of QTc prolongation have been observed in clinical trials. Additionally, concurrent use of other potentially nephrotoxic or hepatotoxic agents should be approached with standard clinical vigilance and appropriate monitoring.

Always inform your healthcare provider about all medications you are currently taking, including prescription medications, over-the-counter drugs, herbal supplements, and vitamins. This comprehensive medication review helps ensure safe and effective treatment. Because dalbavancin has a long half-life, its potential for interactions persists for approximately two weeks after administration, which should be considered if new medications are started during this period.

What Is the Correct Dosage of Dalbavancin Zentiva?

Dalbavancin Zentiva must be administered by a healthcare professional as an intravenous infusion. The powder must first be reconstituted and then further diluted in 5% glucose solution before administration. The infusion should be given over a period of at least 30 minutes to minimize the risk of infusion-related reactions, including Red Man Syndrome. Dalbavancin Zentiva should not be administered as an intravenous bolus injection.

Adults

There are two recommended dosing regimens for Dalbavancin Zentiva in adult patients with ABSSSI:

Both regimens deliver the same total dose of 1,500 mg and have demonstrated comparable clinical efficacy in randomized controlled trials. The choice between single-dose and two-dose administration is at the discretion of the treating physician and may depend on clinical factors such as the severity of the infection, the patient's clinical response, and logistical considerations regarding follow-up visits. The single-dose regimen offers maximum convenience and may be particularly advantageous in settings where patient follow-up is uncertain or where minimizing healthcare visits is a priority.

The 500 mg vials are reconstituted with 25 mL of sterile water for injections to produce a concentrated solution containing 20 mg/mL of dalbavancin. This concentrated solution must then be further diluted in 5% glucose (dextrose) intravenous infusion bags to achieve the appropriate dose. The reconstituted and diluted solution should be a clear, colorless to yellow solution. Do not use if the solution is discolored or contains particulate matter.

Children and Adolescents

Dalbavancin Zentiva is not recommended for use in patients under 18 years of age due to insufficient data on safety and efficacy in this population. Pediatric clinical trials are currently underway to establish appropriate dosing regimens and safety profiles for children. Until these data are available, healthcare providers should use alternative antibiotics with established pediatric dosing for ABSSSI in children and adolescents.

Elderly Patients

No dose adjustment of Dalbavancin Zentiva is required for elderly patients based on age alone. In the phase III clinical trials, approximately 20% of enrolled patients were aged 65 years or older, and no clinically meaningful differences in safety or efficacy were observed between older and younger adults. However, since elderly patients are more likely to have decreased renal function, assessment of creatinine clearance is recommended before treatment, and dose adjustment should be made if severe renal impairment is present (see Renal Impairment section below).

Renal Impairment

Dose adjustment is required in patients with severe renal impairment. The following guidelines apply:

No dose adjustment is necessary for patients on regular hemodialysis because dalbavancin is not significantly removed by hemodialysis due to its high protein binding and large molecular weight. Dalbavancin can be administered without regard to the timing of hemodialysis sessions.

Hepatic Impairment

No dose adjustment is required for patients with mild hepatic impairment (Child-Pugh Class A). Caution is advised in patients with moderate to severe hepatic impairment (Child-Pugh Class B or C) because dalbavancin has not been specifically studied in these populations. Liver function should be monitored in patients with pre-existing hepatic disease, and the potential benefits of treatment should be weighed against the potential risks.

Missed Dose

If the second dose of the two-dose regimen is missed on day 8, it should be administered as soon as possible. There is no established maximum interval between the two doses from clinical trial data. However, the rationale for the day 8 schedule is based on pharmacokinetic modeling showing that the second dose maintains effective drug levels for the remainder of the treatment course. Contact your healthcare provider for guidance if the second dose is significantly delayed.

Overdose

There is limited experience with dalbavancin overdose. In clinical pharmacology studies, healthy subjects have received single intravenous doses of up to 1,500 mg without dose-limiting toxicity. No specific antidote exists for dalbavancin. In the event of overdose, treatment should be supportive with monitoring of clinical status and vital signs. Due to the long half-life of approximately 14 days, patients who receive an overdose may require extended monitoring. Dalbavancin is not efficiently removed by hemodialysis due to its high protein binding.

What Are the Side Effects of Dalbavancin Zentiva?

Like all medications, Dalbavancin Zentiva can cause side effects, although not everybody gets them. The safety profile of dalbavancin has been characterized through phase III clinical trials involving over 1,000 patients receiving dalbavancin for ABSSSI, as well as through post-marketing surveillance. Overall, dalbavancin is well-tolerated, with most adverse reactions being mild to moderate in severity and self-limiting. The overall discontinuation rate due to adverse events in clinical trials was low (approximately 2–3%), comparable to the comparator regimens.

The following frequency classification is used: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (<1/1,000); not known (cannot be estimated from available data).

Infusion-related reactions deserve particular attention. Red Man Syndrome (RMS), characterized by flushing of the upper body, pruritus, urticaria, and/or macular rash, is a well-recognized complication of rapid glycopeptide infusion and is mediated by histamine release from mast cells rather than by a true IgE-mediated allergic mechanism. RMS is largely preventable by ensuring that dalbavancin is infused over at least 30 minutes, as recommended. If RMS occurs, the infusion rate should be slowed or the infusion temporarily stopped, and antihistamines may be administered if symptoms are troublesome.

Hepatic effects have been observed during treatment with dalbavancin, primarily manifesting as transient elevations in ALT, AST, and alkaline phosphatase. In the phase III clinical trials, ALT elevations greater than 3 times the upper limit of normal occurred in approximately 2% of dalbavancin-treated patients compared to approximately 1.5% of comparator-treated patients. Most elevations were asymptomatic and resolved without treatment discontinuation. However, patients with pre-existing liver disease should be monitored, and treatment should be reconsidered if evidence of significant hepatic injury develops.

Clostridioides difficile-associated diarrhea (CDAD) is an important concern with all antibiotic use. Dalbavancin has in vitro activity against C. difficile, and the incidence of CDAD in clinical trials was very low. Nevertheless, CDAD should be considered in any patient who develops diarrhea during or within several weeks after dalbavancin treatment. Given the long half-life of dalbavancin, there is a theoretically extended window during which disruption of normal intestinal flora could occur. If CDAD is confirmed, appropriate therapy should be initiated, which may include oral vancomycin or fidaxomicin.

How Should You Store Dalbavancin Zentiva?

Proper storage of Dalbavancin Zentiva is essential to maintain the potency and safety of the medication. As a hospital-administered intravenous antibiotic, storage and preparation are primarily the responsibility of healthcare professionals and pharmacy departments. However, understanding storage requirements helps ensure appropriate handling throughout the supply chain.

Unopened vials of Dalbavancin Zentiva powder for concentrate for solution for infusion should be stored below 25°C (77°F). The vials do not require refrigeration and should not be frozen. Store in the original packaging to protect from light. The shelf life of the unopened product is as specified on the packaging and is typically 3 years from the date of manufacture when stored under recommended conditions.

After reconstitution with sterile water for injections, the concentrated solution (20 mg/mL) should be used promptly for further dilution. Chemical and physical in-use stability of the reconstituted concentrate has been demonstrated for up to 48 hours at room temperature (20–25°C) or for up to 48 hours when refrigerated at 2–8°C. After dilution in 5% glucose for intravenous infusion, the diluted solution should be used within 48 hours if stored at room temperature or within 48 hours if refrigerated. The total combined storage time of the reconstituted and diluted solution should not exceed 48 hours at room temperature or 48 hours under refrigeration.

From a microbiological point of view, unless the method of reconstitution and dilution precludes the risk of microbial contamination, the product should be used immediately after preparation. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2–8°C. Do not freeze the reconstituted or diluted solution. Any unused medicinal product or waste material should be disposed of in accordance with local requirements for pharmaceutical waste.

Keep Dalbavancin Zentiva and all medicines out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the vial label and carton after “EXP.” The expiry date refers to the last day of that month.

What Does Dalbavancin Zentiva Contain?

Understanding the complete composition of Dalbavancin Zentiva is important for identifying potential allergens and for ensuring compatibility with reconstitution and dilution fluids. The active substance and excipients are detailed below.

Active Substance

Each vial contains 500 mg of dalbavancin (as dalbavancin hydrochloride). Dalbavancin hydrochloride is a semisynthetic lipoglycopeptide with a molecular weight of approximately 1,816 Da. It is a complex glycopeptide structure featuring a heptapeptide aglycone core, two sugar residues (mannose and glucosamine), and a lipophilic C12 acyl side chain attached to the amino sugar. This side chain is critical to the drug's enhanced potency and extended half-life compared to first-generation glycopeptides.

Excipients

• Mannitol (E421): Used as a bulking agent and lyoprotectant to stabilize the active substance during the freeze-drying (lyophilization) manufacturing process. Mannitol helps form an elegant cake structure that facilitates rapid reconstitution.
• Lactose monohydrate: Functions as an additional stabilizer and bulking agent. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not receive this product.
• Hydrochloric acid (for pH adjustment): Used during manufacturing to adjust the pH of the solution prior to lyophilization.
• Sodium hydroxide (for pH adjustment): Used in combination with hydrochloric acid to achieve the target pH of the lyophilized product.

Physical Appearance

Dalbavancin Zentiva is supplied as a sterile, preservative-free, white to off-white to pale yellow lyophilized powder in single-use glass vials. After reconstitution with 25 mL of sterile water for injections, the resulting solution contains 20 mg/mL of dalbavancin and should be a clear, colorless to yellow solution. Inspect the reconstituted solution visually for particulate matter and discoloration before further dilution. Do not use if the solution is turbid or contains visible particles.

Compatibility

Dalbavancin Zentiva should be diluted for infusion using 5% glucose (dextrose) intravenous infusion solution only. It should not be diluted with sodium chloride (saline) solutions, as saline is incompatible and may cause precipitation. Do not mix dalbavancin with other medicinal products or infusion solutions in the same intravenous line. If the same intravenous line is used for sequential infusion of different drugs, the line must be flushed with 5% glucose solution before and after the dalbavancin infusion.