Pharmacotherapeutic Group: Antimicrobial (chemotherapeutic) agents, broad and medium spectrum antibiotics.
Pharmacology: Pharmacodynamics: Zetax-O is an orally-active cephalosporin antibiotic which has in vitro bactericidal activity against a wide variety of gram-positive and gram-negative organisms including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella sp, Haemophilus influenzae (positive and negative β-lacatamases), Moxarella (Branhamella) catarrhalis (positive and negative β-lacatamases). Zetax-O is stable in the presence of β-lactamase enzymes.
Most strains of enterococci (Streptococcus faecalis, group D streptococci) and staphylococci (including coagulase positive and negative strains and methicillin-resistant strains) are resistant to Zetax-O. In addition, most strains of Enterobacter and Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to Zetax-O.
Pharmacokinetics: Zetax-O, given orally, is about 40-50% absorbed whether administered with or without food; however, time to maximal absorption is increased approximately 0.8 hrs when administered with food. A single Zetax-O 200 mg tablet produces an average peak serum concentration (Cmax) of approximately 2 mcg/mL (range 1-4 mcg/mL); a single Zetax-O 100 mg dispersible tablet produces an average Cmax of approximately 1 mcg/mL (range 0.5-2 mcg/mL). Peak serum concentrations occur between 2 and 6 hrs following oral administration of a single 200 mg tablet or a single 100 mg tablet of Zetax-O.
Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hrs. In animal studies, it was noted that Zetax-O is also excreted in the bile in excess of 10% of the administered dose. Serum protein-binding is concentration-independent with a bound fraction of approximately 65%.
The serum half-life (t½) of Zetax-O in healthy subjects is independent of dosage form and averages from 3-4 hrs but may range up to 9 hrs in some normal volunteers. Average area under time curve (AUC) at steady state in elderly patients are approximately 40% higher than average AUC in other healthy adults.
In subjects with moderate renal impairment [creatinine clearance (CrCl) 20-40 mL/min], the average serum t½ of Zetax-O is prolonged to 6.4 hrs. In severe renal impairment (CrCl 5-20 mL/min), the t½ increased to an average of 11.5 hrs. Zetax-O is not cleared significantly from the blood by hemodialysis or peritoneal dialysis. However, a study indicated that with doses of 400 mg, patients undergoing hemodialysis have similar profiles as subjects with CrCl 21-60 mL/min. There is no evidence of metabolism of Zetax-O in vivo.
Take Zetax-O only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.
Shake the oral liquid well before each use. Measure the medicine with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.
Keep using Zetax-O for the full treatment time, even if you feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.
The dose of Zetax-O 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 Zetax-O. 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.
If you miss a dose of Zetax-O, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Store the oral liquid either at room temperature or in the refrigerator. Throw away any unused medicine after 14 days.
Store the tablets in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
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.
Take this medicine with a full glass of water.
Zetax-O works best if you take it with a meal or within 30 minutes of a meal.
The Zetax-O chewable tablet must be chewed before you swallow it.
Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. Breaking the pill may cause too much of the drug to be released at one time.
Shake the oral suspension (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.
This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are using Zetax-O.
Take Zetax-O for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated. Zetax-O will not treat a viral infection such as the common cold or flu.
Store the tablets and capsules at room temperature away from moisture, heat, and light.
Store the oral liquid in the refrigerator. Throw away any unused medication after 14 days.
Zetax-O is a semisynthetic cephalosporin antibacterial drug.
Zetax-O tablets and suspension, given orally, are about 40% to 50% absorbed whether administered with or without food; however, time to maximal absorption is increased approximately 0.8 hours when administered with food. A single 200 mg tablet of Zetax-O produces an average peak serum concentration of approximately 2 mcg/mL (range 1 to 4 mcg/mL); a single 400 mg tablet produces an average peak concentration of approximately 3.7 mcg/mL (range 1.3 to 7.7 mcg/mL). The oral suspension produces average peak concentrations approximately 25% to 50% higher than the tablets, when tested in normal adult volunteers. Two hundred and 400 mg doses of oral suspension produce average peak concentrations of 3 mcg/mL (range 1 to 4.5 mcg/mL) and 4.6 mcg/mL (range 1.9 to 7.7 mcg/mL), respectively, when tested in normal adult volunteers. The area under the time versus concentration curve (AUC) is greater by approximately 10% to 25% with the oral suspension than with the tablet after doses of 100 to 400 mg, when tested in normal adult volunteers. This increased absorption should be taken into consideration if the oral suspension is to be substituted for the tablet. Crossover studies of tablet versus suspension have not been performed in children.
The 400 mg capsule is bioequivalent to the 400 mg tablet under fasting conditions. However, food reduces the absorption following administration of the capsule by approximately 15% based on AUC and 25% based on Cmax.
Peak serum concentrations occur between 2 and 6 hours following oral administration of a single 200 mg tablet, a single 400 mg tablet or 400 mg of Zetax-O suspension. Peak serum concentrations occur between 2 and 5 hours following a single administration of 200 mg of suspension. Peak serum concentrations occur between 3 and 8 hours following oral administration of a single 400 mg capsule.
Serum protein binding is concentration independent with a bound fraction of approximately 65%. In a multiple dose study conducted with a research formulation which is less bioavailable than the tablet or suspension, there was little accumulation of drug in serum or urine after dosing for 14 days. Adequate data on CSF levels of Zetax-O are not available.
Metabolism and Excretion
There is no evidence of metabolism of Zetax-O in vivo. Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hours. In animal studies, it was noted that Zetax-O is also excreted in the bile in excess of 10% of the administered dose. The serum half-life of Zetax-O in healthy subjects is independent of dosage form and averages 3 to 4 hours but may range up to 9 hours in some normal volunteers.
Geriatrics: Average AUCs at steady state in elderly patients are approximately 40% higher than average AUCs in other healthy adults. Differences in the pharmacokinetic parameters between 12 young and 12 elderly subjects who received 400 mg of Zetax-O once daily for 5 days are summarized as follows:
|Pharmacokinetic Parameters (mean ± SD) for Zetax-O in Both Young & Elderly Subjects|
|Cmax (mg/L)||4.74 ± 1.43||5.68 ± 1.83|
|Tmax (h)*||3.9 ± 0.3||4.3 ± 0.6|
|AUC (mg.h/L)*||34.9 ± 12.2||49.5 ± 19.1|
|T½ (h)*||3.5 ± 0.6||4.2 ± 0.4|
|Cave (mg/L)*||1.42 ±0.50||1.99 ± 0.75|
|*Difference between age groups was significant. (p<0.05)|
However, these increases were not clinically significant.
Renal Impairment: In subjects with moderate impairment of renal function (20 to 40 mL/min creatinine clearance), the average serum half-life of Zetax-O is prolonged to 6.4 hours. In severe renal impairment (5 to 20 mL/min creatinine clearance), the half-life increased to an average of 11.5 hours. The drug is not cleared significantly from the blood by hemodialysis or peritoneal dialysis. However, a study indicated that with doses of 400 mg, patients undergoing hemodialysis have similar blood profiles as subjects with creatinine clearances of 21 to 60 mL/min.
Mechanism of Action
As with other cephalosporins, the bactericidal action of Zetax-O results from inhibition of cell wall synthesis. Zetax-O is stable in the presence of certain beta-lactamase enzymes. As a result, certain organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases may be susceptible to Zetax-O.
Resistance to Zetax-O in isolates of Haemophilus influenzae and Neisseria gonorrhoeae is most often associated with alterations in penicillin-binding proteins (PBPs). Zetax-O may have limited activity against Enterobacteriaceae producing extended spectrum beta-lactamases (ESBLs). Pseudomonas species, Enterococcus species, strains of Group D streptococci, Listeria monocytogenes, most strains of staphylococci (including methicillin-resistant strains), most strains of Enterobacter species, most strains of Bacteroides fragilis, and most strains of Clostridium species are resistant to Zetax-O.
Zetax-O has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications And Usage (1).
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Zetax-O against isolates of similar genus or organism group. However, the efficacy of Zetax-O in treating clinical infections caused by to these bacteria has not been established in adequate and well-controlled clinical trials.
For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.
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Information checked by Dr. Sachin Kumar, MD Pharmacology