Dalbavancin Teva

What Is Dalbavancin Teva and What Is It Used For?

Dalbavancin belongs to the lipoglycopeptide class of antibiotics, a group that also includes telavancin and oritavancin. These antibiotics are structurally related to vancomycin but have been chemically modified with a lipophilic side chain that enhances their antimicrobial potency and extends their duration of action. Dalbavancin is a semi-synthetic derivative of the naturally occurring glycopeptide A-40926, produced by the actinomycete Nonomuraea species.

The primary approved indication for dalbavancin is the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults. ABSSSI is a collective term that encompasses several types of skin infections requiring systemic antibiotic therapy, including cellulitis and erysipelas (spreading skin infections), wound infections (both surgical and traumatic), and major cutaneous abscesses (abscesses affecting a significant body surface area with surrounding cellulitis).

Dalbavancin works by binding to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of the stem pentapeptide in nascent peptidoglycan, the major structural polymer of bacterial cell walls. This binding prevents the transglycosylation and transpeptidation reactions necessary for cross-linking peptidoglycan strands, ultimately inhibiting cell wall synthesis and causing bacterial cell death. The lipophilic side chain anchors dalbavancin to the bacterial cell membrane, increasing the drug's local concentration and contributing to its enhanced potency compared to vancomycin.

The spectrum of activity of dalbavancin covers most clinically relevant Gram-positive organisms. It demonstrates potent bactericidal activity against Staphylococcus aureus (including both methicillin-susceptible and methicillin-resistant strains), Streptococcus pyogenes (Group A Streptococcus), Streptococcus agalactiae (Group B Streptococcus), Streptococcus anginosus group, Streptococcus dysgalactiae, and Enterococcus faecalis (vancomycin-susceptible strains only). It is not effective against Gram-negative bacteria, fungi, or viruses.

One of the most distinctive pharmacological features of dalbavancin is its exceptionally long terminal elimination half-life of approximately 346 hours (about 14.4 days). This is the longest half-life of any approved antibiotic, enabling clinicians to treat infections that traditionally require 7 to 14 days of intravenous antibiotics with as few as one or two infusions. This characteristic has significant implications for patient convenience, healthcare resource utilization, and the potential to reduce hospital stays or avoid hospitalization altogether.

What Should You Know Before Taking Dalbavancin Teva?

Contraindications

Dalbavancin is contraindicated in patients with a known hypersensitivity to dalbavancin or to any of its excipients. Patients with a history of serious allergic reactions to other glycopeptide antibiotics such as vancomycin or teicoplanin should use dalbavancin with extreme caution, as cross-sensitivity may occur. If a severe allergic reaction or anaphylaxis occurs during infusion, the administration must be stopped immediately and appropriate emergency treatment initiated.

There are no absolute contraindications based on organ function, but dose adjustments may be necessary for patients with significant renal impairment. Specifically, patients with an estimated creatinine clearance below 30 mL/min who are not receiving regular haemodialysis require a dose reduction. Regular monitoring of renal function is recommended during treatment in patients with pre-existing kidney disease.

Warnings and Precautions

Hypersensitivity reactions, including anaphylaxis, have been reported with dalbavancin use. Healthcare providers must be prepared to manage anaphylactic reactions when administering dalbavancin. Patients should be observed during and for a period after the infusion is completed. If an allergic reaction occurs, treatment should be discontinued and supportive care provided.

Infusion-related reactions resembling Red Man Syndrome can occur if dalbavancin is infused too rapidly. Red Man Syndrome is characterized by flushing, erythema, pruritus, and urticaria, predominantly affecting the upper body, face, and neck. To minimize this risk, dalbavancin should be infused over at least 30 minutes. If an infusion-related reaction occurs, slowing or temporarily stopping the infusion typically resolves symptoms.

As with virtually all antibacterial agents, Clostridioides difficile-associated diarrhea (CDAD) has been reported with dalbavancin use. CDAD can range in severity from mild diarrhea to fatal colitis. Patients who develop diarrhea during or after treatment with dalbavancin should be evaluated for CDAD, particularly if the diarrhea is severe, persistent, or accompanied by abdominal pain or fever.

Dalbavancin may cause hepatic enzyme elevations. Patients with pre-existing liver disease or those receiving concurrent hepatotoxic medications should be monitored with periodic liver function tests. Although clinically significant hepatotoxicity is uncommon, cases of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported in clinical trials.

Superinfection with non-susceptible organisms, including fungi and resistant bacteria, may occur during treatment. If superinfection is suspected or confirmed, appropriate measures should be taken, including discontinuation of dalbavancin if necessary and initiation of targeted antimicrobial therapy.

Pregnancy and Breastfeeding

There are limited clinical data on the use of dalbavancin in pregnant women. Animal reproductive studies have not demonstrated direct or indirect harmful effects with respect to embryo-fetal development, parturition, or postnatal development. However, as a precautionary measure, dalbavancin should only be used during pregnancy if the potential benefit to the mother justifies the potential risk to the fetus. Women of childbearing potential should discuss family planning with their healthcare provider before starting treatment.

It is not known whether dalbavancin is excreted in human breast milk. Given the potential for adverse effects in the breastfed infant, a decision should be made whether to discontinue breastfeeding or to abstain from dalbavancin therapy, taking into account the importance of the drug to the mother. If the drug is deemed essential, temporary cessation of breastfeeding may be recommended, though the long half-life of dalbavancin means that the drug may persist in the mother's body for several weeks after the last dose.

How Does Dalbavancin Teva Interact with Other Drugs?

In vitro studies have shown that dalbavancin is not metabolized by cytochrome P450 (CYP450) enzymes and does not significantly inhibit or induce CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 at clinically relevant concentrations. This pharmacokinetic profile suggests a low potential for drug-drug interactions mediated through the CYP450 system, which is a notable advantage over many other antibiotics.

Dalbavancin is highly protein-bound (approximately 93%), primarily to albumin. While theoretical displacement interactions with other highly protein-bound drugs are possible, clinical studies have not demonstrated clinically significant interactions of this type. Nonetheless, concomitant use with drugs that have a narrow therapeutic index and are also highly protein-bound (such as warfarin) should be accompanied by appropriate monitoring.

As with other glycopeptide antibiotics, concurrent use with other potentially nephrotoxic or ototoxic agents warrants careful monitoring. Although dalbavancin itself has a favorable renal safety profile, additive effects on the kidneys or inner ear cannot be excluded when used alongside aminoglycosides (e.g., gentamicin, tobramycin), loop diuretics (e.g., furosemide), or other nephrotoxic drugs.

Major Interactions

Minor Interactions

What Is the Correct Dosage of Dalbavancin Teva?

Dalbavancin Teva is supplied as a 500 mg powder for concentrate for solution for infusion. The powder must be reconstituted and then further diluted before administration as an intravenous infusion. The reconstituted and diluted solution should be a clear, colorless to yellow solution. Only a qualified healthcare professional should prepare and administer the infusion.

Adults

For the treatment of ABSSSI in adults, dalbavancin may be administered according to one of two approved regimens. The single-dose regimen consists of 1500 mg administered as a single intravenous infusion over 30 minutes. The two-dose regimen consists of 1000 mg administered as an IV infusion over 30 minutes on Day 1, followed by 500 mg administered as an IV infusion over 30 minutes on Day 8 (one week later).

Clinical trials, including the DISCOVER 1 and DISCOVER 2 phase III studies, demonstrated that both regimens are equally effective and non-inferior to a comparator regimen of vancomycin (with optional switch to oral linezolid) for 10 to 14 days. The single-dose regimen offers the additional advantage of completing the entire course of antibiotic therapy in a single visit, which may be particularly beneficial for patients who have difficulty adhering to multi-day treatment plans or returning for follow-up appointments.

Children and Adolescents

The safety and efficacy of dalbavancin have not been established in pediatric patients under the age of 18 years. Therefore, dalbavancin is not currently recommended for use in children and adolescents. Pediatric clinical trials are ongoing, and dosing recommendations for this population may be established in the future as further data become available. In some regions, investigational use in adolescents has been explored, but no formal pediatric approval exists at this time.

Elderly Patients

No dose adjustment is required for elderly patients based on age alone. In clinical trials, patients 65 years of age and older showed comparable safety and efficacy profiles to younger adults. However, elderly patients are more likely to have reduced renal function, and renal function should be assessed to determine whether dose adjustment is necessary. Monitoring for adverse effects, particularly renal function changes and infusion-related reactions, is recommended in this population.

Renal Impairment

No dose adjustment is required for patients with mild to moderate renal impairment (estimated creatinine clearance 30 mL/min or greater). For patients with severe renal impairment (estimated creatinine clearance less than 30 mL/min) who are not receiving regular haemodialysis, the recommended dose is reduced. Under the single-dose regimen, 1000 mg should be administered instead of 1500 mg. Under the two-dose regimen, 750 mg should be given on Day 1 and 375 mg on Day 8. No dose adjustment is needed for patients on regular haemodialysis, as dalbavancin is not significantly removed by dialysis.

Missed Dose

If a patient on the two-dose regimen misses the Day 8 dose, it should be administered as soon as possible. Given dalbavancin's long half-life, the second dose can be given up to several days after the scheduled Day 8 appointment without significant loss of efficacy. However, the treating physician should assess the clinical response and determine whether any additional therapy is needed. If the delay exceeds two weeks, clinical re-evaluation is recommended.

Overdose

There is limited experience with dalbavancin overdose. In clinical trials, total doses of up to 4500 mg were administered without clinically significant adverse effects. In the event of an overdose, the patient should be monitored and supportive care provided as needed. Dalbavancin is not significantly removed by haemodialysis (less than 6% of a dose is removed during a 3-hour session), so dialysis is not expected to be useful in the management of overdose.

What Are the Side Effects of Dalbavancin Teva?

Like all medicines, dalbavancin can cause side effects, although not everybody experiences them. Clinical trials involving more than 2,000 patients treated with dalbavancin have provided comprehensive safety data. The majority of adverse reactions were mild to moderate in severity and did not require discontinuation of treatment. Below are the side effects organized by frequency of occurrence.

The most clinically significant adverse reaction to be aware of is anaphylaxis, which is a medical emergency requiring immediate treatment with epinephrine, airway management, and supportive care. Patients who have experienced allergic reactions to glycopeptide antibiotics in the past are at higher risk and should discuss this with their healthcare provider before receiving dalbavancin.

Red Man Syndrome, also known as vancomycin flushing syndrome or red neck syndrome, can occur with dalbavancin as with other glycopeptide antibiotics. It is not a true allergic reaction but rather a histamine-mediated response to rapid infusion. Symptoms include diffuse flushing, erythema, and pruritus, primarily affecting the face, neck, and upper torso. Slowing the infusion rate or pretreating with antihistamines can prevent or mitigate this reaction.

Gastrointestinal side effects such as nausea, diarrhea, and vomiting are the most frequently reported adverse events in clinical trials. These are typically mild and self-limiting. However, as noted above, persistent or severe diarrhea should prompt evaluation for Clostridioides difficile infection, which can be life-threatening and requires specific treatment with oral vancomycin or fidaxomicin.

How Should You Store Dalbavancin Teva?

Dalbavancin Teva is supplied as a lyophilized powder in single-use glass vials. The unopened vials should be stored at a temperature not exceeding 25°C (77°F). The vials should be kept in the original outer carton to protect the powder from light. Do not freeze the unopened vials.

After reconstitution with sterile water for injection, the concentrated solution should be a clear, colorless to yellow solution free of visible particles. The reconstituted vial can be stored for up to 48 hours at 2–8°C (36–46°F). After further dilution with 5% dextrose (glucose) solution for intravenous infusion, the diluted solution remains stable for up to 48 hours at room temperature (20–25°C) or under refrigeration (2–8°C).

Any unused medicinal product or waste material should be disposed of in accordance with local requirements for pharmaceutical waste. Dalbavancin vials are single-use only and any unused reconstituted solution should be discarded after the recommended storage period. Do not use the product if the reconstituted or diluted solution is cloudy, discolored, or contains particulate matter.

What Does Dalbavancin Teva Contain?

The active substance in Dalbavancin Teva is dalbavancin. Each vial contains 500 mg of dalbavancin (as dalbavancin hydrochloride). After reconstitution with 25 mL of sterile water for injection, each mL of the concentrated solution contains 20 mg of dalbavancin.

The excipients (inactive ingredients) serve important functions in maintaining the stability and physical properties of the lyophilized powder:

• Mannitol: Acts as a bulking agent and cryoprotectant during the freeze-drying (lyophilization) process, helping to maintain the structural integrity of the powder cake.
• Lactose monohydrate: Serves as an additional bulking agent and stabilizer. Patients with rare hereditary conditions of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should discuss this with their healthcare provider.
• Hydrochloric acid and/or sodium hydroxide: Used for pH adjustment to achieve the target pH of the reconstituted solution (approximately 3.5 to 4.5), ensuring stability and compatibility with intravenous administration.

After reconstitution, the solution must be further diluted with 5% dextrose (glucose) intravenous infusion solution to achieve the appropriate concentration for intravenous administration. The solution should not be mixed with or administered simultaneously through the same intravenous line with other medications. If the same intravenous line is used for sequential infusion of different drugs, the line should be flushed with 5% dextrose solution before and after dalbavancin administration.

Dalbavancin is incompatible with saline-based diluents. The reconstituted and diluted solution should only use 5% dextrose solution as the diluent. Use of sodium chloride (saline) solutions can cause precipitation of the drug.