Teicoplanin package insert pdf

In the study of hospitalized pediatric patients birth through 11 years with Gram-positive infections, who were randomized 2 to 1 linezolid: vancomycin , mortality was 6. However, given the severe underlying illness in the patient population, no causality could be established. Of the pediatric patients treated for uSSSIs, Of the pediatric patients treated for uSSSIs, 1.

For all other indications, discontinuations due to drug-related adverse events occurred in 0. ZYVOX has been associated with thrombocytopenia when used in doses up to and including mg every 12 hours for up to 28 days. Thrombocytopenia associated with the use of ZYVOX appears to be dependent on duration of therapy generally greater than 2 weeks of treatment.

No related clinical adverse events were identified in Phase 3 clinical trials in patients developing thrombocytopenia. Bleeding events were identified in thrombocytopenic patients in a compassionate use program for ZYVOX; the role of linezolid in these events cannot be determined [ see Warnings and Precautions 5.

Changes seen in other laboratory parameters, without regard to drug relationship, revealed no substantial differences between ZYVOX and the comparators. These changes were generally not clinically significant, did not lead to discontinuation of therapy, and were reversible. The incidence of adult and pediatric patients with at least one substantially abnormal hematologic or serum chemistry value is presented in Tables 4, 5, 6, and 7.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:. Linezolid is a reversible, nonselective inhibitor of monoamine oxidase [ see Contraindications 4. Linezolid has the potential for interaction with adrenergic and serotonergic agents [ see Warnings and Precautions 5. Available data from published and postmarketing case reports with linezolid use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

When administered during organogenesis, linezolid did not cause malformations in mice, rats, or rabbits at maternal exposure levels approximately 6. However, embryo-fetal lethality was observed in mice at 6. When female rats were dosed during organogenesis through lactation, postnatal survival of pups was decreased at doses approximately equivalent to the estimated human exposure based on AUCs see Data.

The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U. In mice, embryo-fetal toxicities were observed only at doses that caused maternal toxicity clinical signs and reduced body weight gain. Fetal malformations were not observed. The effects consisted of decreased fetal body weights and reduced ossification of sternebrae, a finding often seen in association with decreased fetal body weights.

Male and female pups permitted to mature to reproductive age, when mated, showed an increase in preimplantation loss. Linezolid is present in breast milk. There is no information on the effects of linezolid on the breastfed infant; however, diarrhea and vomiting were the most common adverse reactions reported in clinical trials in infants receiving linezolid therapeutically [ see Adverse Reactions 6.

There is no information on the effects of linezolid on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for linezolid and any potential adverse effects on the breastfed child from linezolid or from the underlying maternal condition. The safety and effectiveness of ZYVOX for the treatment of pediatric patients with the following infections are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from a comparator-controlled study of Gram-positive infections in pediatric patients ranging in age from birth through 11 years [ see Indications and Usage 1 , Clinical Pharmacology The safety and effectiveness of ZYVOX for the treatment of pediatric patients with the following infection have been established in a comparator-controlled study in pediatric patients ranging in age from 5 through 17 years [ see Clinical Studies 14 ]:.

Pharmacokinetic information generated in pediatric patients with ventriculoperitoneal shunts showed variable cerebrospinal fluid CSF linezolid concentrations following single and multiple dosing of linezolid; therapeutic concentrations were not consistently achieved or maintained in the CSF. Therefore, the use of linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended.

The pharmacokinetics of linezolid have been evaluated in pediatric patients from birth to 17 years of age. In general, weight-based clearance of linezolid gradually decreases with increasing age of pediatric patients. However, pediatric patients exhibit wider variability in linezolid clearance and systemic exposure AUC compared with adults. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

In the event of overdosage, supportive care is advised, with maintenance of glomerular filtration. Hemodialysis may facilitate more rapid elimination of linezolid. Data are not available for removal of linezolid with peritoneal dialysis or hemoperfusion. The chemical name for linezolid is S -N-[[3-[3-Fluoro 4-morpholinyl phenyl]oxooxazolidinyl] methyl]-acetamide.

Its molecular weight is Injection is supplied as a ready-to-use sterile isotonic solution for intravenous infusion. Each mL contains 2 mg of linezolid. Inactive ingredients are dextrose monohydrate Inactive ingredients are carnauba wax, corn starch, hydroxypropylcellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and titanium dioxide.

Following constitution, each 5 mL contains mg of linezolid. Inactive ingredients are aspartame, citric acid, colloidal silicon dioxide, flavors, mannitol, microcrystalline cellulose and carboxymethylcellulose sodium, sodium benzoate, sodium chloride, sodium citrate, sucrose, and xanthan gum [ see Patient Counseling Information 17 ]. At both the mg and 1, mg ZYVOX doses, no significant effect on QTc interval was detected at peak plasma concentration or at any other time.

The mean pharmacokinetic parameters of linezolid in adults after single and multiple oral and intravenous doses are summarized in Table 8. Plasma concentrations of linezolid at steady-state after oral doses of mg given every 12 hours are shown in Figure 1. Figure 1. Linezolid is extensively absorbed after oral dosing. Therefore, linezolid may be given orally or intravenously without dose adjustment.

Linezolid may be administered without regard to the timing of meals. The time to reach the maximum concentration is delayed from 1. Animal and human pharmacokinetic studies have demonstrated that linezolid readily distributes to well-perfused tissues. The volume of distribution of linezolid at steady-state averaged 40 to 50 liters in healthy adult volunteers. Linezolid concentrations have been determined in various fluids from a limited number of subjects in Phase 1 volunteer studies following multiple dosing of linezolid.

The ratio of linezolid in saliva relative to plasma was 1. Linezolid is primarily metabolized by oxidation of the morpholine ring, which results in two inactive ring-opened carboxylic acid metabolites: the aminoethoxyacetic acid metabolite A , and the hydroxyethyl glycine metabolite B. Formation of metabolite A is presumed to be formed via an enzymatic pathway whereas metabolite B is mediated by a non-enzymatic chemical oxidation mechanism in vitro. In vitro studies have demonstrated that linezolid is minimally metabolized and may be mediated by human cytochrome P However, the metabolic pathway of linezolid is not fully understood.

A small degree of nonlinearity in clearance was observed with increasing doses of linezolid, which appears to be due to lower renal and nonrenal clearance of linezolid at higher concentrations. However, the difference in clearance was small and was not reflected in the apparent elimination half-life.

The pharmacokinetics of linezolid are not significantly altered in elderly patients 65 years or older. Therefore, dose adjustment for geriatric patients is not necessary. The pharmacokinetics of linezolid following a single intravenous dose were investigated in pediatric patients ranging in age from birth through 17 years including premature and full-term neonates , in healthy adolescent subjects ranging in age from 12 through 17 years, and in pediatric patients ranging in age from 1 week through 12 years.

The pharmacokinetic parameters of linezolid are summarized in Table 9 for the pediatric populations studied and healthy adult subjects after administration of single intravenous doses. The C max and the volume of distribution V ss of linezolid are similar regardless of age in pediatric patients. However, plasma clearance of linezolid varies as a function of age. As the age of pediatric patients increases, the weight-based clearance of linezolid gradually decreases, and by adolescence mean clearance values approach those observed for the adult population.

There is increased inter-subject variability in linezolid clearance and systemic drug exposure AUC across all pediatric age groups as compared with adults. Similar mean daily AUC values were observed in pediatric patients from birth to 11 years of age dosed every 8 hours relative to adolescents or adults dosed every 12 hours.

Pediatric patients 12 years and older should receive mg every 12 hours [ see Dosage and Administration 2 ]. Females have a slightly lower volume of distribution of linezolid than males. Plasma concentrations are higher in females than in males, which is partly due to body weight differences.

However, there are no significant gender differences in mean apparent elimination-rate constant or half-life. Thus, drug exposure in females is not expected to substantially increase beyond levels known to be well tolerated. Therefore, dose adjustment by gender does not appear to be necessary. The pharmacokinetics of the parent drug, linezolid, are not altered in patients with any degree of renal impairment; however, the two primary metabolites of linezolid accumulate in patients with renal impairment, with the amount of accumulation increasing with the severity of renal dysfunction see Table The pharmacokinetics of linezolid and its two metabolites have also been studied in patients with end-stage renal disease ESRD receiving hemodialysis.

In the ESRD study, 14 patients were dosed with linezolid mg every 12 hours for Because similar plasma concentrations of linezolid are achieved regardless of renal function, no dose adjustment is recommended for patients with renal impairment.

However, given the absence of information on the clinical significance of accumulation of the primary metabolites, use of linezolid in patients with renal impairment should be weighed against the potential risks of accumulation of these metabolites. Both linezolid and the two metabolites are eliminated by hemodialysis. No information is available on the effect of peritoneal dialysis on the pharmacokinetics of linezolid.

On the basis of the available information, no dose adjustment is recommended for patients with mild-to-moderate hepatic impairment. The pharmacokinetics of linezolid in patients with severe hepatic impairment have not been evaluated.

Linezolid is not an inducer of cytochrome P CYP in rats. It can also be used for manual strip application. Strips are contained in cartridges which hold 10 strips. There are 10 cartridges per box for a total of strips. There is an integrated desiccant in each cartridge and each box comes with a re-sealable lid for enhanced storage stability.

Order online or learn more! Order online! Evolution of antimicrobial resistance among Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in Brooklyn, NY. J Antimicrob Chemother. Poster : Friday - J Clin Microbiol. Vancomycin-resistant Staphylococcus aureus isolate from a patient in Pennsylvania. Antimicrob Agents Chemother. Clinical failures of linezolid and implications for the clinical microbiology laboratory. Emerg Infect Dis. Clin Pharmacokinet.

Recommended initial loading dose of teicoplanin, established by therapeutic drug monitoring, and outcome in terms of optimal trough level. The assessment of MRSA infection remedy based on therapeutic monitoring of teicoplanin. Jpn J Ther Drug Monit. Development of a teicoplanin-nomogram for accurately maintaining correct dosages. J Jpn Soc Hosp Pharm. Download references. Financial support for this study was provided by the Japan Society for the Promotion of Science You can also search for this author in PubMed Google Scholar.

Correspondence to Yasuo Takeda. Kanazawa, N. An initial dosing method for teicoplanin based on the area under the serum concentration time curve required for MRSA eradication.

J Infect Chemother 17, — Download citation. Received : 27 January Accepted : 16 July Rare or very rare Abscess ; red man syndrome.

Frequency not known Agranulocytosis ; angioedema ; chills ; neutropenia ; overgrowth of nonsusceptible organisms ; renal impairment ; seizure ; severe cutaneous adverse reactions SCARs ; thrombophlebitis. Side-effects, further information Teicoplanin is associated with a lower incidence of nephrotoxicity than vancomycin. Cross sensitivity Caution if history of vancomycin sensitivity. Manufacturer advises use only if potential benefit outweighs risk. No information available. Monitor renal and auditory function during prolonged treatment in renal impairment.

Therapeutic drug monitoring With intramuscular use or intravenous use Manufacturer advises monitor serum-teicoplanin trough concentration at steady state after completion of loading dose and during maintenance treatment—consult product literature. Blood counts and liver and kidney function tests required.

Manufacturer advises injection can be used to prepare solution for oral administration.