Posology : מינונים

4.2        Posology and method of administration

Posology
Linezan solution for infusion may be used as initial therapy. Patients who commence treatment on the parenteral formulation may be switched to either oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as linezolid has an oral biovailability of approximately 100%.

The solution for infusion should be administered over a period of 30 to 120 minutes.

The recommended linezolid dosage should be administered IV or orally twice daily.
The recommended dosage for Linezan formulations for the treatment of infections is described in Table 1.

Table 1. Dosage Guidelines for
Linezan
Dosage and Route of Administration           Recommended
Pediatric Patients†     Adults and             Duration of Treatment Infection*           (Birth through 11 Years      Adolescents (12        (consecutive days) of                           Years and Older)
Age)
Complicated skin and skin structure infections
Community- acquired            10 mg/kg IV or oral‡ q8h     600 mg IV or oral‡           10 to 14 pneumonia,                                       q12h including concurrent bacteremia
Nosocomi al pneumoni a
Vancomycin- resistant           10 mg/kg IV or oral‡ q8h     600 mg IV or oral‡             14 to Enterococcus                                     q12h                            28 faecium infections,
including concurrent bacteremia
Uncomplicated        <5 yrs: 10 mg/kg            Adults: 400 mg oral‡ skin and skin                 oral‡ q8h         q12h Adolescents: 600           10 to structure           5-11 yrs: 10 mg/kg              mg oral‡ q12h                14 infections                   oral‡ q12h



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 Due to the designated pathogens (see THERAPEUTIC INDICATIONS)
Neonates <7 days: Most pre-term neonates < 7 days of age (gestational age < 34 weeks) have lower systemic linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg q12h.
Consideration may be given to the use of 10 mg/kg q8h regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg q8h by 7 days of life (see PHARMACOLOGICAL PROPERTIES, Pharmacokintic Properties, Pediatric).
Oral dosing using linezolid tablets

Adult patients with infection due to MRSA should be treated with Linezan 600 mg q12h.

In limited clinical experience, 5 out of 6 (83%) pediatric patients with infections due to Gram-positive pathogens with MICs of 4 µg/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 µg/mL, lower systemic exposure, site and severity of infection, and the underlying medical condition should be considered when assessing clinical response (see
PHARMACOLOGICAL PROPERTIES, Pharmacokinetic Properties,
Pediatric and Special Warnings and Special Precautions for Use, Pediatric Use).

In controlled clinical trials, the protocol-defined duration of treatment for all infections ranged from 7 to 28 days. Total treatment duration was determined by the treating physician based on site and severity of the infection, and on the patient’s clinical response.

No dose adjustment is necessary when switching from intravenous to oral administration. Patients whose therapy is started with Linezan I.V. Injection may be switched to linezolid tablets at the discretion of the physician, when clinically indicated.

Elderly patients: No dose adjustment is required.

Female patients: No dose adjustment is required.
Patients with renal insufficiency: No dose adjustment is required (see section 5.2). Patients with mild to moderate renal insufficiency: (ie CLCR> 30 ml/min}: No dose adjustment is required.

Patients with severe renal insufficiency CLCR < 30 ml/min): No dose adjustment is required. Due to the unknown clinical significance of higher exposure (up to 10 fold) to the two primary metabolites of linezolid in patients with severe renal insufficiency, linezolid should be used with special caution in these patients and only when the anticipated benefit is considered to outweigh the theoretical risk. As approximately 30% of a linezolid dose is removed during 3 hours of hemodialysis, linezolid should be given after dialysis in patients receiving such treatment. The primary metabolites of linezolid are removed to some extent by hemodialysis, but the concentrations of these metabolites are still very considerably higher following dialysis than those observed in patients with normal renal function or mild to moderate renal insufficiency. Therefore, linezolid should be used with special Page 3 of 24
caution in patients with severe renal insufficiency who are undergoing dialysis and only when the anticipated benefit is considered to outweigh the theoretical risk. To date, there is no experience of linezolid administration to patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal failure (other than haemodialysis).

Patients with impaired hepatic function: No dose adjustment is required.
However, there are no pharmacokinetic data and limited clinical experience of linezolid in patients with severe hepatic insufficiency. Linezolid should be used with special caution in patients with severe hepatic insufficiency and only when the anticipated benefit is considered to outweigh the theoretical risk.