LINEZOLID tablet

Država: Združene države Amerike

Jezik: angleščina

Source: NLM (National Library of Medicine)

Aktivna sestavina:

LINEZOLID (UNII: ISQ9I6J12J) (LINEZOLID - UNII:ISQ9I6J12J)

Dostopno od:

Amneal Pharmaceuticals LLC

INN (mednarodno ime):

LINEZOLID

Sestava:

LINEZOLID 600 mg

Pot uporabe:

ORAL

Tip zastaranja:

PRESCRIPTION DRUG

Terapevtske indikacije:

Linezolid tablets are indicated for the treatment of nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant isolates) or Streptococcus pneumoniae [see Clinical Studies (14)] . Linezolid tablets are indicated for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae , including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible isolates only) [see Clinical Studies (14)] . Linezolid tablets are indicated for the treatment of complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis, caused by Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus pyogenes , or Streptococcus agalactiae . Linezolid tablets has not been studied in the treatment of decubitus ulcers [see Clinical Studies (14)] . Linezolid tablets are indicated for the treatment of uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes [see Clinical Studies (14)] . Linezolid tablets are indicated for the treatment of vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia [see Clinical Studies (14)] . - Linezolid tablets are not indicated for the treatment of Gram-negative infections. It is critical that specific Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected [see Warnings and Precautions (5.4)]. - The safety and efficacy of linezolid formulations given for longer than 28 days have not been evaluated in controlled clinical trials [see Clinical Studies (14)]. To reduce the development of drug-resistant bacteria and maintain the effectiveness of linezolid tablets and other antibacterial drugs, linezolid tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Linezolid formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components. Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g., phenelzine, isocarboxazid) or within two weeks of taking any such medicinal product. Risk Summary Available data from published and post-marketing 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 6.5 times (mice), equivalent to (rats), or 0.06 times (rabbits) the clinical therapeutic exposure, based on AUCs. However, embryo-fetal lethality was observed in mice at 6.5 times the estimated human exposure. 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.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In mice, embryo-fetal toxicities were observed only at doses that caused maternal toxicity (clinical signs and reduced body weight gain). An oral dose of 450 mg/kg/day given from Gestation Day (GD) 6 to 16 (6.5 times the estimated human exposure based on AUCs) correlated with increased post-implantational embryo death, including total litter loss, decreased fetal body weights, and an increased incidence of costal cartilage fusion. Neither maternal nor embryo-fetal toxicities were observed at doses up to 150 mg/kg/day. Fetal malformations were not observed. In rats, fetal toxicity was observed at 15 mg/kg/day and 50 mg/kg/day administered orally from GD 6 to 17 (exposures 0.22 times to approximately equivalent to the estimated human exposure, respectively, based on AUCs). The effects consisted of decreased fetal body weights and reduced ossification of sternebrae, a finding often seen in association with decreased fetal body weights. Fetal malformations were not observed. Maternal toxicity, in the form of reduced body weight gain, was seen at 50 mg/kg/day. In rabbits, reduced fetal body weight occurred only in the presence of maternal toxicity (clinical signs, reduced body weight gain and food consumption) when administered at an oral dose of 15 mg/kg/day given from GD 6 to 20 (0.06 times the estimated human exposure based on AUCs). Fetal malformations were not observed. When female rats were treated with 50 mg/kg/day (approximately equivalent to the estimated human exposure based on AUCs) of linezolid during pregnancy and lactation (GD 6 through Lactation Day 20), survival of pups was decreased on postnatal days 1 to 4. Male and female pups permitted to mature to reproductive age, when mated, showed an increase in preimplantation loss. Risk Summary Linezolid is present in breast milk. Based on data from available published case reports, the daily dose of linezolid that the infant would receive from breastmilk would be approximately 6% to 9% of the recommended therapeutic infant dose (10 mg/kg every 8 hours). 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 (6.1)] and (see Clinical Considerations). 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. Clinical Considerations Advise lactating women to monitor a breastfed infant for diarrhea and vomiting. Infertility Males Based on findings from studies in rats, linezolid may reversibly impair fertility in male patients [see Nonclinical Toxicology (13.1)]. The safety and effectiveness of linezolid 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 (12.3) and Clinical Studies (14)] : - nosocomial pneumonia - complicated skin and skin structure infections - community-acquired pneumonia (also supported by evidence from an uncontrolled study in patients ranging in age from 8 months through 12 years) - vancomycin-resistant Enterococcus faecium infections The safety and effectiveness of linezolid 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)] : - uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible strains only) or Streptococcus pyogenes 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, in preterm (gestational age < 34 weeks) neonates < 7 days of age, linezolid clearance is often lower than in full-term neonates < 7 days of age. Consequently, preterm neonates < 7 days of age may need an alternative linezolid dosing regimen of 10 mg/kg every 12 hours [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)] . In limited clinical experience, 5 out of 6 (83%) pediatric patients with infections due to Gram-positive pathogens with minimum inhibitory concentrations (MICs) of 4 mcg/mL treated with linezolid had clinical cures. However, pediatric patients exhibit wider variability in linezolid clearance and systemic exposure (AUC) compared with adults. In pediatric patients with a sub-optimal clinical response, particularly those with pathogens with MIC of 4 mcg/mL, lower systemic exposure, site and severity of infection, and the underlying medical condition should be considered when assessing clinical response [see Clinical Pharmacology (12.3) and Dosage and Administration (2)] . Of the 2,046 patients treated with linezolid in Phase 3 comparator-controlled clinical trials, 589 (29%) were 65 years or older and 253 (12%) were 75 years or older. 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.

Povzetek izdelek:

Linezolid tablets, 600 mg are supplied as white to off-white, modified capsule shaped, film-coated tablets debossed with “AN 777” on one side and plain on the other side. They are available as follows: Bottles of 20:                                      NDC 65162-777-02 Bottles of 30:                                      NDC 65162-777-03 Bottles of 100:                                    NDC 65162-777-10 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Keep bottles tightly closed to protect from moisture.

Status dovoljenje:

Abbreviated New Drug Application

Lastnosti izdelka

LINEZOLID- LINEZOLID TABLET
AMNEAL PHARMACEUTICALS LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LINEZOLID TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR LINEZOLID
TABLETS.
LINEZOLID TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2000
RECENT MAJOR CHANGES
Warnings and Precautions, Myelosuppression (5.1) 7/2023
INDICATIONS AND USAGE
Linezolid tablets are an oxazolidinone-class antibacterial indicated
in adults and children for the treatment
of the following infections caused by susceptible Gram-positive
bacteria: Nosocomial pneumonia (1.1);
Community-acquired pneumonia (1.2); Complicated skin and skin
structure infections, including diabetic
foot infections, without concomitant osteomyelitis (1.3);
Uncomplicated skin and skin structure infections
(1.4); Vancomycin-resistant _Enterococcus faecium _infections. (1.5)
Limitations of Use (1.6):
Linezolid tablets are not indicated for the treatment of Gram-negative
infections.
The safety and efficacy of linezolid formulations given for longer
than 28 days have not been evaluated
in controlled clinical trials.
To reduce the development of drug-resistant bacteria and maintain the
effectiveness of linezolid
formulations and other antibacterial drugs, linezolid tablets should
be used only to treat or prevent
infections that are proven or strongly suspected to be caused by
bacteria. (1.7)
DOSAGE AND ADMINISTRATION
DOSAGE, ROUTE, AND FREQUENCY OF
ADMINISTRATION
INFECTION
PEDIATRIC PATIENTS
(2)
(BIRTH THROUGH 11
YEARS OF AGE)
ADULTS AND ADOLESCENTS (2)
(12 YEARS AND OLDER)
DURATION
(2)
(DAYS)
Nosocomial pneumonia
10 mg/kg oral every
8 hours
600 mg oral every 12 hours
10 to 14
Community-acquired pneumonia,
including concurrent bacteremia
Complicated skin and skin structure
infections
Vancomycin-resistant _Enterococcus_
_faecium_ infections, including
concurrent bacteremia
10 mg/kg oral every
8 hours
600 mg oral every 12 hours
14 to 28
Uncomplicated skin and skin structure
infections
les