Overview:
Dalbavancin is a second-generation lipoglycopeptide antibiotic that improves glycopeptides of the present antibiotic Vancomycin. It treats acute bacterial and skin structure infections by gram-positive microorganisms. The gram-positive bacteria against which it acts are Staphylococcus aureus, S. pyrogens, S. agalactiae, S. dysgalactiae, S. anginosus group, and Enterococcus faecalis. Dalbavancin works by interfering with these bacterial cell wall syntheses.
Indications of Dalbavancin:
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Acute Bacterial and Skin Structure Infections- Skin infections caused by gram-positive bacteria, which include Staphylococcus aureus (Methicillin-susceptible and methicillin-resistant strains), Streptococcus pyrogens, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group, and Enterococcus faecalis.
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To reduce the resistance of antibacterial drugs and maintain their effectiveness, Dalbavancin, and other antibacterial drugs.
Dosage:
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Dosage Form - Presented in clear glass vials containing sterile powder equivalent to 500 mg of Dalbavancin; injected intravenously.
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Dose Strength - 500 mg of lyophilized powder in the vial for reconstitution.
Administration:
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Recommended Dosage - A dose of 1500 mg is given in patients. It is administered as a single or 1000 mg dose followed by one week with 500 mg. Dalbavancin is to be issued in 30 minutes by intravenous infusion.
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In Renal Impairment Patients - In patients with less creatinine clearance, even less than 30 mL/min, the recommended dose of Dalbavancin is 1125 mg as a single dose or 750 mg followed by 375 mg one week later.
Contraindications:
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It is contraindicated in patients who are hypersensitive to Dalbavancin.
Special Considerations:
- Pregnancy - There are no relevant studies done on pregnant women. Dalbavancin is used in pregnancy cautiously.
- Lactating Mothers - There are no studies about Dalbavancin on lactating mothers excreting metabolites in milk. The cautious use of Dalbavancin is done in these cases.
- Pediatric Population - The safety and efficacy of the drug is not determined in child patients.
- Geriatric Population - The side effects of Dalbavancin can be severe in old patients and even more in patients with kidney impairments. Care is taken in selecting the dosage.
- Kidney Impairment Patient - A patient with less creatinine clearance not receiving hemodialysis is recommended 1125 mg dosage, given as a single dosage or divided into two dosages of 750 mg and 375 mg, which is given after one week gap.
- Hepatic Impairments - Mild, moderate, and severe hepatic impairments have different dosage adjustments for patients. Cautious use of the Dalbavancin is done in them.
Warning and Precautions:
- Hypersensitivity Reactions - If any patient is being reported with hypersensitivity reactions, anaphylactic reactions, or skin allergic reactions while using Dalbavancin, discontinuation of the drug should be done soon.
- Any Infusion-Related Reactions - If the intravenous infusion shows a response like "red man syndrome," the drug should be stopped, or a slow injection should minimize the reaction.
- Hepatic Effects - The hepatic results can be abnormal with the regular use of Dalbavancin.
- Clostridium Difficile-Associated Diarrhea - Using antibacterial drugs has disturbed the normal flora of the colon and thus the growth of the Clostridium difficile. If any results present Clostridium difficile, then fluid and electrolyte management is done to eradicate them.
- Drug-Resistance Bacteria - Dalbavancin is recommended for strongly suspected bacterial infection; if given unnecessarily can develop drug-resistant bacteria.
For Patients:
What Is Dalbavancin?
Dalbavancin is a medicine used to treat acute bacterial and skin structure infections. It is an antibacterial medicine used against gram-positive bacteria only, like Staphylococcus aureus and Streptococcus pyrogens.
Why Is Dalbavancin Medicine Prescribed?
Dalbavancin is prescribed to treat skin infections caused by a particular group of bacteria. It stops the bacteria from synthesizing their cell walls and killing them. Using antibiotics when not needed can increase the risk of getting infections.
How Is It Used?
Dalbavancin is administered through injections. The injection comes as a powder to be mixed with the fluid and given into the vein over 30 minutes. It is presented in a single shot or once a week with two shots.
What Is the Precaution While Using Dalbavancin Medicine?
Precautions while using Dalbavancin medicine are:
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The patient may experience an allergic or hypersensitivity reaction after the injection of Dalbavancin. Itchiness or rash can appear with sudden symptoms like reddening the face, neck, or upper chest. The patient should consult the doctor after he finds any allergic reaction symptoms.
What Should the Patient Inform the Doctor Before Dalbavancin Use?
The patient should inform the information before the doctor recommends Dalbavancin is:
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Inform the doctor about the pregnancy.
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Inform the doctor about the medicine the patient is regularly taking.
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Inform the doctor about the patient's medical condition, especially if the patient has kidney or liver disease.
What Is the Diet Required With Dalbavancin?
Dalbavancin medicine does not require any special diet, and the patient can continue with the regular diet while having Dalbavancin.
What if a Dose Is Missed?
If the patient missed the injection, then the patient should call the doctor soon to get his missed dose.
What Are the Side Effects of Dalbavancin Medicine?
Side effects of the Dalvancin medicine are:
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Nausea.
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Vomiting.
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Headache.
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Diarrhea.
Some of the side effects can be serious. If any side effects appear below, then consult the doctor soon.
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Hives.
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Rashes.
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Itchiness.
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Difficulty in breathing.
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Difficulty in swallowing.
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Fever.
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Severe diarrhea.
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Stomach cramps.
What Are the Important Points While Using Dalbavancin Medicine?
Important points are:
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Regular appointments with the doctor are important.
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Keep the doctor informed about the side effects after using Dalbavancin.
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The patient should notify the doctor of the medication he is regularly taking.
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The patient should tell the doctor about the medical condition related to liver or kidney diseases.
For Doctors:
Dalbavancin:
Dalbavancin is a mixture of five active homologs of A and B components (A0, A1, B0, B1, and B2). B0 is the major component. Homologs have similar core structures but are dissimilar in the fatty acid side chain of N-acyl aminoglyucuronic acid.
Dalbavancin is supplied in clear glass vials containing sterile, lyophilized, preservative-free powder, which is presented in white, off-white, or pale colors, equivalent to 500 mg of Dalbavancin.
Indications:
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The Dalbavancin drug mainly treats acute bacterial and skin structure infections caused by gram-positive bacteria. Some of the gram-positive bacteria against which Dalbavancin drug works are Staphylococcus aureus (methicillin-susceptible and Methicillin-resistant strains), Streptococcus pyrogens, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group, and Enterococcus faecalis.
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To reduce the resistance of antibacterial drugs and maintain their effectiveness, Dalbavancin, and other antibacterial drugs.
Mechanism of Action:
Dalbavancin has a mechanism similar to the Vancomycin drug. It mainly works to interfere with the synthesis of bacteria's cell walls. It prevents N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) peptide subunits from being incorporated into the peptidoglycan matrix (a component of the cell wall matrix of the bacteria). The large hydrophilic part forms a hydrogen bond with the terminal D-alanyl-D-alanine of NAM/NAG peptides. Dalbavancin binding to D-Ala-D-Ala prevents NAM/NAG peptide subunits from binding with the peptidoglycan matrix. Dalbavancin also changes bacterial cell membrane permeability with RNA synthesis.
Pharmacokinetics:
- Absorption: Dalbavancin has increased proportionally to dose following a single intravenous Dalbavancin dose from 140 mg to 1500 mg, indicating linear pharmacokinetics. There was no accumulation of Dalbavancin in multiple infusions also.
- The Volume of Distribution: Clearance and distribution at a steady state are similar to extracellular fluid volume.
- Protein Binding: Dalbavancin is bound to plasma protein, mainly albumin. Ninety-three percent is plasma protein binding of the Dalbavancin drug.
- Metabolism: The metabolites of the Dalbavancin drug are not present in a significant amount in the human plasma. Hydroxy-dalbavancin and mannosyl aglycone is present in the urine of the patient.
- Elimination: An average of 33% of the administered Dalbavancin drug dose is eliminated in urine as unchanged Dalbavancin, and only 12% was eliminated in urine as a metabolite. 20% of the administered dose was excreted in feces.
- Half-Life: The half-life of Dalbavancin is 346 hours.
- Clearance of Dalbavancin: The clearance of Dalbavancin is 0.0513L/h.
- Toxicity: Dalbavancin's toxicity can change the colon's flora and even form the growth of Clostridium difficile, which is associated with diarrhea.
Drug Interaction:
- Drug Laboratory Test Interaction - No relevant reports have been present for drug laboratory test interaction. Dalbavancin does not prolong the prothrombin time (PT) or activate partial thromboplastin time (aPTT).
- Drug-Drug Interaction - No studies related to drug-drug interactions are present. There are very few interactions of drugs between Dalbavancin and cytochrome P450 (CYP450) substrates or inhibitors.
Dosage and Administration:
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Dalbavancin is marketed in clear glass vials containing sterile powder equivalent to 500 mg of Dalbavancin.
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The patient with normal kidney functions is administered 1500 mg either as a single dose or 1000 mg, followed by one week later with 500 mg.
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The patient with a less creatinine clearance, even less than 30 mL/min, and not on hemodialysis, is administered 1125 mg of a single dose or two doses, one of 750 mg, followed by 375 mg after one week. No adjustment for a patient with hemodialysis.
Preparation and Administration:
Dalbavancin is delivered by injection after reconstituting it with sterile water, USP, or 5% Dextrose injection and subsequently diluting it with 5% Dextrose injection or USP to a specific concentration limit of 1 mg/mL to 5 mg/mL.
Reconstitution - Dalbavancin is reconstituted under aseptic conditions with 25 mL of sterile water, USP, or 5% Dextrose injection, and USP is used for each 500 mg vial. Do not shake to avoid foaming, and gently swirl. The reconstituted vial contains 20 mg/mL Dalbavancin (clear colorless yellow solution).
Storage - Reconstituted vials are stored in the refrigerator at 2 to 8 degree Celsius. (36 to 46 degrees F), or at room temperature of 20 to 25 degrees Celsius, do not freeze the medicine.
Dilution - The dose required is transferred from the reconstituted Dalbavancin solution vials to the intravenous bag containing 5 % Dextrose injection, USP. The diluted solution has a final Dalbavancin concentration of 1 mg/mL. Dispose of the unrequired reconstituted solution. The time from reconstitution to dilution to administration should be within 48 hours.
Administration - After dilution, it is administered by intravenous infusion, taking 30 minutes to infuse. Do not infuse it with other drugs, electrolytes, or a saline-based infusion solution. If common intravenous access is used to administer other medications, flush the line before administering Dalbavancin infusion.
Contraindication:
Hypersensitivity to the Dalbavancin drug in the patient is the contraindication. If hypersensitivity develops during usage, then the Dalbavancin is discontinued.
Special Considerations:
- Pregnancy - Dalbavancin is used cautiously in pregnancy as no relevant studies are present.
- Breastfeeding Mothers - Cautious use of Dalbavancin is recommended in breastfeeding mothers as no studies on lactating mothers are present.
- Pediatric - Dalbavancin safety and efficacy are not determined in child patients under 12 years of age.
- Geriatric - Dalbavancin can show ill results than good results in old patients. Care is taken in selecting the dosage.
- Kidney Impairment - In the patient with less creatinine clearance which is even less than 30 mL/min, and who is not receiving hemodialysis. The recommended dose is 1125 mg for kidney impairment patients, which can be given in a single dose, or 750 mg followed by 375 mg one week.
- Hepatic Impairments - The dosage recommended for patients with mild hepatic impairments does not require any adjustment. Cautious use of Dalbavancin is recommended in these patients.
Warning and Precautions:
- Hypersensitivity Reactions - The drug is discontinued if the patient encounters hypersensitivity or anaphylactic reactions while using Dalbavancin.
- Any Infusion-Related Reactions - If the intravenous infusion-related reaction appears, the drug should be stopped, or a slow infusion should be performed to minimize the reaction.
- Hepatic Effects - The liver faces a change with regular use of Dalbavancin, and thus hepatic effects can appear.
- Clostridium Difficile-Associated Diarrhea - As the use of antibacterial drugs disturbs the normal flora of the colon and causes the growth of Clostridium difficile. If the patient reports colon changes and Clostridium difficile, then fluid and electrolyte management is done to eradicate it.
- Drug-Resistance Bacteria - Dalbavancin is recommended for strongly suspected bacterial infection; if the use of Dalbavancin is for other bacteria or infections, chances of the development of drug-resistant bacteria can occur.
Overdosage:
The treatment of the overdosage should consist of supportive measures. However, no information is present for treating an overdose of Dalbavancin.
Specific Population:
- Renal Impairments - No dosage adjustment is necessary for creatinine clearance greater than 30 mL/min or for the hemodialysis patient. Patients with end-stage renal diseases should regularly schedule hemodialysis (three times/week), similar to those with subjects with mild to moderate renal impairments, as less than 6% of the dose delivered to these end-stage patients gets excreated in three hours after hemodialysis.
- Hepatic Impairments - The decreased dose of 28 % to 31 % in patients with moderate to severe hepatic impairments. No dosage adjustment is recommended in mild hepatic changes patients. But still, cautious use of the drug is done in hepatic impairment patients.
- Gender - No dosage adjustment is based on gender.
- Geriatric Patients - No dosage adjustment is recommended for old age people.
- Pediatric Patient - Patients under 12 years of age are given Dalbavancin, as no data has been established on them.
Clinical Trials:
Acute Bacterial and Skin Structure Infections
- Dalbavancin Two-Dose Regimen (1000 mg day 1:500 mg day 8) - Patients with acute bacterial skin and skin structure infections were in Phase 3, randomized, double-blind, double-dummy clinical trials (trial and trial 2). There were a total of 1312 patients. Patients have been treated with a two-dose regimen of Dalbavancin (1000 mg and 500 mg after one week) or intravenous Vancomycin (1125 mg) given as 750 mg and 375 mg in one week.
- Primary Endpoint - The patient has no increase from baseline in the lesion area 48 to 72 hours after initiation of the therapy. It has a temperature consistently at or below 37.6 degrees Celsius.
- Secondary Endpoint - The total patient achieved a 20% or more significant deduction in the lesion area after 48 to 72 hours. And the clinical success rate was viewed in follow-up visits between 26 to 30 days was presented by a decrease in lesion size, lower temperature, and local signs started resolving.
- Dalbavancin 1500mg Single Dose Regimen - Patients with acute bacterial and skin structure infections were taken in phase 3, double-blind clinical trials. A randomized population of 698 patients was treated with a Dalbavancin single dose of 1500 mg or a two-dose regimen of 1000 mg and 500 mg after one week (trial 3).
- Primary Endpoint - The patient with a 20 % deduction in the lesion area was 48 to 72 hours, randomization without receiving any antibacterial drug.
- Secondary Endpoint - The clinical success rate at follow-up visit between 26 to 30 days, a 90 % decrease in lesion size, lower temperature, and local signs start resolving.
Results:
In trials 1, 2, and 3, every patient's blood cultures were taken, and 40 patients among them had bacteremia at baseline by one or other bacteria. Thirty-four patients were clinical responders at 48 to 72 hours, and 32 were clinical successes at 26 to 30 days.
