Vancomycin Fresenius Kabi Actions

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Actions of Vancomycin Fresenius Kabi in details

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The bactericidal action of Vancomycin Fresenius Kabi results primarily from inhibition of cell-wall biosynthesis. Specifically, Vancomycin Fresenius Kabi prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Normally this is a five-point interaction. This binding of Vancomycin Fresenius Kabi to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. In addition, Vancomycin Fresenius Kabi alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between Vancomycin Fresenius Kabi and other antibiotics. Vancomycin Fresenius Kabi is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.

How should I take Vancomycin Fresenius Kabi?

Some medicines given by injection may sometimes be given at home to patients who do not need to be in the hospital for the full time of treatment. If you are receiving Vancomycin Fresenius Kabi at home, make sure you clearly understand and carefully follow your doctor's instructions.

To help clear up your infection completely, Vancomycin Fresenius Kabi must be given for the full time of treatment, even if you begin to feel better after a few days. Also, Vancomycin Fresenius Kabi works best when there is a constant amount in the blood. To help keep the amount constant, Vancomycin Fresenius Kabi must be given on a regular schedule.

Dosing

The dose of Vancomycin Fresenius Kabi will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Vancomycin Fresenius Kabi. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

Vancomycin Fresenius Kabi administration

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Intravenous: Administer Vancomycin Fresenius Kabi with a final concentration not to exceed 5 mg/mL by IV intermittent infusion over at least 60 minutes (recommended infusion period of ≥30 minutes for every 500 mg administered [ASHP/IDSA/SIDP {Rybak 2009}]); in adult patients in need of fluid restriction, a concentration up to 10 mg/mL may be used, but risk of infusion-related reactions is increased. Not for IM administration.

If a maculopapular rash appears on the face, neck, trunk, and/or upper extremities (red man syndrome), slow the infusion rate to over 1/ to 2 hours and increase the dilution volume (Healy 1990; Rybak 1986; Szymusiak-Mutnick 1996). Hypotension, shock, and cardiac arrest (rare) have also been reported with too rapid of infusion. Administration of antihistamines prior to infusion may prevent or minimize this reaction (Rybak 1986; Wilhem 1999).

Irritant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Information conflicts regarding the use of dry cold or dry warm compresses (Hurst 2004; Reynolds 2014); however, dry warm compresses may be of benefit in increasing local blood flow to enhance drug removal from the extravasation site. Intradermal hyaluronidase may be considered for refractory cases (Reynolds 2014).

Hyaluronidase: Intradermal: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) along injection site and edematous area (Reynolds 2014).

Antibiotic lock technique (off-label use): Instill prepared Vancomycin Fresenius Kabi lock solution into each lumen of the catheter access port using a volume sufficient to fill the catheter (2 to 5 mL) with a dwell time of 48 to 72 hours (dependent on frequency of catheter use). Withdraw lock solution prior to catheter use; replace with fresh Vancomycin Fresenius Kabi lock solution after catheter use (IDSA [Mermel 2009]; LaPlante 2007).

Intraventricular (off-label route): Use preservative-free preparations only. May be administered intraventricularly with a final concentration of 2.5 to 10 mg/mL for the treatment of CSF shunt infections. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow Vancomycin Fresenius Kabi solution to equilibrate in the CSF (IDSA [Tunkel 2004; Tunkel 2017]; Ng 2014).

Intravitreal (off-label route): May administer Vancomycin Fresenius Kabi intravitreally with a final concentration of 1 mg/0.1 mL NS or sterile water (Durand 2019; Kelsey 1995).

Oral:

Solution (Firvanq): Shake reconstituted oral solution well before each use.

Injection: Reconstituted powder for injection (not premixed solution) may be diluted and used for oral administration; common flavoring syrups may be added to improve taste. The unflavored, diluted solution may also be administered via nasogastric tube.

Rectal (off-label route): May be administered as a retention enema per rectum (IDSA/SHEA [McDonald 2018]); 500 mg in 100 to 500 mL of NS, volume may depend on length of segment being treated. If sodium chloride causes hyperchloremia could use solution with lower chloride concentration (eg, LR) (ACG [Surawicz 2013]).

Vancomycin Fresenius Kabi pharmacology

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Mechanism of Action

Vancomycin Fresenius Kabi is an antibacterial drug.

Pharmacokinetics

Vancomycin Fresenius Kabi is poorly absorbed after oral administration. During multiple dosing of 250 mg every 8 hours for 7 doses, fecal concentrations of Vancomycin Fresenius Kabi in volunteers exceeded 100 mg/kg in the majority of samples. No blood concentrations were detected and urinary recovery did not exceed 0.76%. In anephric subjects with no inflammatory bowel disease who received Vancomycin Fresenius Kabi oral solution 2 g for 16 days, blood concentrations of Vancomycin Fresenius Kabi were less than or equal to 0.66 μg/mL in 2 of 5 subjects. No measurable blood concentrations were attained in the other 3 subjects. Following doses of 2 g daily, concentrations of drug were >3100 mg/kg in the feces and <1 μg/mL in the serum of subjects with normal renal function who had C. difficile-associated diarrhea. After multiple-dose oral administration of Vancomycin Fresenius Kabi, measurable serum concentrations may occur in patients with active C. difficile-associated diarrhea, and, in the presence of renal impairment, the possibility of accumulation exists. It should be noted that the total systemic and renal clearances of Vancomycin Fresenius Kabi are reduced in the elderly.

Microbiology

Mechanism of Action

The bactericidal action of Vancomycin Fresenius Kabi against Staphylococcus aureus and the vegetative cells of Clostridium difficile results primarily from inhibition of cell-wall biosynthesis.

In addition, Vancomycin Fresenius Kabi alters bacterial-cell-membrane permeability and RNA synthesis.

Mechanism of resistance

Staphylococcus aureus:

S. aureus isolates with Vancomycin Fresenius Kabi minimal inhibitory concentrations (MICs) as high as 1024 mcg/mL have been reported.

The exact mechanism of this resistance is not clear but is believed to be due to cell wall thickening and potentially the transfer of genetic material.

Clostridium difficile: Isolates of C. difficile generally have Vancomycin Fresenius Kabi MICs of <1 mcg/mL, however Vancomycin Fresenius Kabi MICs ranging from 4 mcg/mL to 16 mcg/mL have been reported. The mechanism which mediates C. difficile's decreased susceptibility to Vancomycin Fresenius Kabi has not been fully elucidated.

Vancomycin Fresenius Kabi has been shown to be active against susceptible isolates of the following bacteria in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-positive bacteria

Staphylococcus aureus (including methicillin-resistant isolates) associated with enterocolitis

Anaerobic Gram-positive bacteria

Clostridium difficile isolates associated with C. difficile associated diarrhea.



References

  1. NCIt. "Vancomycin: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).

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Information checked by Dr. Sachin Kumar, MD Pharmacology

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