Actions of Vonxim in details
Pharmacology: In vivo bactericidal activity of Vonxim Axetil is due to Vonxim's binding to essential target proteins and the resultant inhibition of cell wall synthesis.
Vonxim has bactericidal activity against a wide range of common pathogens, including many beta-lactamase producing strains. Vonxim is stable to many bacterial beta-lactamases, especially plasmid-mediated enzymes that are commonly found in enterobacteriaceae.
Pharmacokinetics: Vonxim Axetil is absorbed from the gastrointestinal tract and is rapidly hydrolysed in the intestinal mucosa and blood to Vonxim; absorption is enhanced in the presence of food. Peak plasma concentrations are reported about 2 to 3 hours after an oral dose. The sodium salt is given by intramuscular or intravenous injection. Peak plasma concentrations of about 27 micrograms/mL have been achieved 45 minutes after an intramuscular dose of 750 mg with measurable amounts present 8 hours after a dose. Up to 50% of Vonxim in the circulation is bound to plasma proteins. The plasma half-life is about 70 minutes and is prolonged in patients with renal impairment and in neonates. Vonxim is widely distributed in the body including pleural fluid, sputum, bone, synovial fluid, and aqueous humour, but only achieves therapeutic concentrations in the CSF when the meninges are inflamed. It crosses the placenta and has been detected in breast milk.
Vonxim is excreted unchanged, by glomerular filtration and renal tubular secretion, and high concentrations are achieved in the urine. On injection, most of a dose of Vonxim is excreted within 24 hours, the majority within 6 hours. Probenecid competes for renal tubular secretion with Vonxim resulting in higher and more prolonged plasma concentrations of Vonxim. Small amounts of Vonxim are excreted in bile.
Plasma concentrations are reduced by dialysis.
How should I take Vonxim?
Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.
You may take Vonxim tablets with or without meals.
Vonxim oral suspension (liquid) must be taken with food.
Shake the oral liquid well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
If you switch from using the tablet form to using the oral suspension (liquid) form of Vonxim, you may not need to use the same exact dosage in number of milligrams. The medication may not be as effective unless you use the exact form and strength your doctor has prescribed.
Use this medication for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated. Vonxim will not treat a viral infection such as the common cold or flu.
This medication can cause you to have false results with certain medical tests, including urine glucose (sugar) tests. Tell any doctor who treats you that you are using Vonxim.
Store Vonxim tablets at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.
Store Vonxim oral liquid in the refrigerator. Do not allow it to freeze. Throw away any unused medication that is older than 10 days.
Vonxim administration
Oral suspension: Administer with food. Shake well before use.
Oral tablet: May administer with or without food. Swallow tablet whole (crushed tablet has strong, persistent, bitter taste).
IM: Inject deep IM into large muscle mass.
IV: Inject direct IV over 3 to 5 minutes. Infuse intermittent infusion over 15 to 30 minutes.
Vonxim pharmacology
Following IV doses of 750 mg and 1.5 g, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of Vonxim (Vonxim (Vonxim injection) injection) in the serum following IV administration of 1.5 g doses every 8 hours to normal volunteers. The serum half-life after IV injection is approximately 80 minutes.
Approximately 89% of a dose of Vonxim (Vonxim (Vonxim injection) injection) is excreted by the kidneys over an 8 hour period, resulting in high urinary concentrations.
Intravenous doses of 750 mg and 1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL, respectively, during the first 8 hour period.
The concomitant oral administration of probenecid with Vonxim (Vonxim (Vonxim injection) injection) slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Vonxim (Vonxim (Vonxim injection) injection) is detectable in therapeutic concentrations in pleural fluid, joint fluid, bile, sputum, bone, cerebrospinal fluid (in patients with meningitis), and aqueous humor.
Vonxim (Vonxim (Vonxim injection) injection) is detectable in therapeutic concentrations in cerebrospinal fluid (CSF) of adults and pediatric patients with meningitis. The following table shows the concentrations of Vonxim (Vonxim (Vonxim injection) injection) achieved in cerebrospinal fluid during multiple dosing of patients with meningitis.
Table 1. Concentrations of Vonxim (Vonxim (Vonxim injection) injection) Achieved in Cerebrospinal Fluid During Multiple Dosing of Patients with Meningitis
Patients | Dose | Number of Patients | Mean (Range) CFS Vonxim (Vonxim (Vonxim injection) injection) Concentrations (mcg/mL) Achieved Within 8 Hours Post Dose |
Pediatric patients (4 weeks to 6.5 years) | 200 mg/kg/day, divided q 6 hours | 5 | 6.6 (0.9-17.3) |
Pediatric patients (7 months to 9 years) | 200 to 230 mg/kg/day, divided q 8 hours | 6 | 8.3 (<2-22.5) |
Adults | 1.5 grams q 8 hours | 2 | 5.2 (2.7-8.9) |
Adults | 1.5 grams q 6 hours | 10 | 6.0 (1.5-13.5) |
Vonxim (Vonxim (Vonxim injection) injection) is approximately 50% bound to serum protein.
Microbiology: Vonxim (Vonxim (Vonxim injection) injection) has in vitro activity against a wide range of gram-positive and gram-negative organisms, and it is highly stable in the presence of beta-lactamases of certain gram-negative bacteria. The bactericidal action of Vonxim (Vonxim (Vonxim injection) injection) results from inhibition of cell-wall synthesis.
Vonxim (Vonxim (Vonxim injection) injection) is usually active against the following organisms in vitro.
Aerobes, Gram-positive
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae, and
Streptococcus pyogenes (and other streptococci)
NOTE: Most strains of enterococci, e.g., Enterococcus faecalis (formerly Streptococcus faecalis), are resistant to Vonxim (Vonxim (Vonxim injection) injection). Methicillin-resistant staphylococci and Listeria monocytogenes are resistant to Vonxim (Vonxim (Vonxim injection) injection).
Aerobes, Gram-negative
Citrobacter spp.
Enterobacter spp.
Escherichia coli
Haemophilus influenzae (including ampicillin-resistant strains)
Haemophilus parainfluenzae
Klebsiella spp. (including Klebsiella pneumoniae)
Moraxella (Branhamella) catarrhalis (including ampicillin- and cephalothin-resistant strains)
Morganella morganii (formerly Proteus morganii)
Neisseria gonorrhoeae (including penicillinase- and non-penicillinase-producing strains)
Neisseria meningitidis
Proteus mirabilis
Providencia rettgeri (formerly Proteus rettgeri)
Salmonella spp., and Shigella spp.
NOTE: Some strains of Morganella morganii, Enterobacter cloacae, and Citrobacter spp. have been shown by in vitro tests to be resistant to Vonxim (Vonxim (Vonxim injection) injection) and other cephalosporins. Pseudomonas and Campylobacter spp., Acinetobacter calcoaceticus, and most strains of Serratia spp. and Proteus vulgaris are resistant to most first- and second-generation cephalosporins.
Anaerobes: Gram-positive and gram-negative cocci (including Peptococcus and Peptostreptococcus spp.), gram-positive bacilli (including Clostridium spp.), and gram-negative bacilli (including Bacteroides and Fusobacterium spp.).
NOTE: Clostridium difficile and most strains of Bacteroides fragilis are resistant to Vonxim (Vonxim (Vonxim injection) injection).
Susceptibility Tests
Diffusion Techniques
Quantitative methods that require measurement of zone diameters give an estimate of antibiotic susceptibility. One such standard procedure (broth, agar, microdilution) or equivalent with Vonxim (Vonxim (Vonxim injection) injection) powder. The MIC values obtained for bacterial isolates other than Haemophilus spp. and Neisseria gonorrhoeae should be interpreted according to the following criteria:
MIC (mcg/mL) | Interpretation |
≤ 8 | (S) Susceptible |
16 | (MS) Moderately Susceptible |
≥ 32 | (R) Resistant |
MIC values obtained for Haemophilus spp. should be interpreted according to the following criteria:
MIC (mcg/mL) | Interpretation |
≤ 4 | (S) Susceptible |
8 | (I) Intermediate |
≥ 16 | (R) Resistant |
MIC values obtained for Neisseria gonorrhoeae should be interpreted according to the following criteria:
MIC (mcg/mL) | Interpretation |
≤ 1 | (S) Susceptible |
2 | (MS) Moderately Susceptible |
≥ 4 | (R) Resistant |
As with standard diffusion techniques, dilution methods require the use of laboratory control organisms. Standard Vonxim (Vonxim (Vonxim injection) injection) powder should provide the following MIC values.
1. For organisms other than Haemophilus spp. and Neisseria gonorrhoeae:
Organism | MIC (mcg/mL) |
Staphylococcus aureus ATCC 29213 | 0.5-2.0 |
Escherichia coli ATCC 25922 | 2.0-8.0 |
2. For Haemophilus spp.:
Organism | MIC (mcg/mL) |
Haemophilus influenzae ATCC 49766 | 0.25-1.0 |
3. For Neisseria gonorrhoeae:
Organism | MIC (mcg/mL) |
Neisseria gonorrhoeae ATCC 49226 | 0.25-1.0 |
Staphylococcus aureus ATCC 29213 | 0.25-1.0 |
REFERENCES
1. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing. Third Informational Supplement. NCCLS Document M100-S3, Vol. 11, No. 17, Villanova, PA: NCCLS; 1991.
References
- NCIt. "Cefuroxime: 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