PHARMACOLOGY

Pharmacotherapeutic Group:oxazolidinone 

Pharmacodynamic Properties:Linezolid is an bacteriostatic oxazolidinone, inhibiting ribosomal protein synthesis at the level of the 23s ribosome of the 50s subunit. It is active against gram-positive bacteria including vancomycin-resistant enterococci and MRSA. It has limited in-vitro activity against gram-negative bacteria.

 Pharmacokinetic Properties:

Absorption: Oral bioavaiability: Approximately 100%. Rapidly absorbed after oral admin. Peak plasma concentrations after 1-2 hours, although delayed if administered with high fat meal.

Distribution: Plasma protein binding: Approximately 31%. Readily distributed into well perfused tissues, bone, fat, lungs, muscle, skin blister fluids and CSF. Volume of distribution at steady state: 40-50 liter.

Metabolism:  Oxidised to 2 main inactive metabolites.

Excretion: Approximately 65% of dose eliminated via non renal route. Renal clearance is low. Elimination half life: 4.6-7 hours (oral).

INDICATIONS

Nosocomial Pneumonia, Community acquired pneumonia, Complicated and Uncomplicated skin and skin structure Infections, Vancomycin resistant Enterococcus Faecium Infecions

Dosage and Administration

Adult: 600 mg oral every 12 hours

 ADVERSE DRUG REACTIONS

Diarrhoea (antibiotic associated colitis reported), headache, nausea, vomiting, constipation, abnormal liver function tests, fever, vaginal and oral candidiasis, skin rash, pruritus, dizziness, insomnia, anaemia, tongue discoloration, taste disturbance, lactic acidosis, optic and peripheral neuropathy (particularly if used ≥ 28 days).
Potentially Fatal: Reversible myelosuppression including anaemia, leukopenia, pancytopenia and thrombocytopenia (particularly if using > 10-14 days), transient ischaemic attacks, renal failure, Stevens-Johnson syndrome.

 PRECAUTIONS

Preexisting myelosuppression, renal impairment (CrCl < 30ml/min), uncontrolled hypertension, phaeochromocytoma, carcinoid syndrome, untreated hyperthyroidism, chronic infection, history of seizures, bipolar depression, schizophrenia or acute confusional states. Pregnancy and lactation. Monitor complete blood counts weekly. Give after haemodialysis. Not known if linezolid or metabolites removed during peritoneal dialysis.

 DRUG INTERACTIONS

May reduce serum level with rifampin and phenytoin. May cause hypoglycemia with insulin or oral antidiabetics. May increase risk of seizures with tramadol. Increased risk of serotonin syndrome with  Monoamine oxidase inhibitors (MAOIs), Tricyclic Antidepressants (TCAs), Serotonin-norepinephrine reuptake inhibitors (SNRIs), or other serotonergic drugs (e.g. bupropion, vilazodone, mirtazapine, meperidine, trazodone, nefazodone). Significant increase in blood pressure with vasopressive agents (e.g. epinephrine, norepinephrine), sympathomimetic agents (e.g. pseudoephrine) & dopaminergic agents (e.g. dopamine, dobutamine)

 CONTRAINDICATIONS

Patients with a known allergy to linezolid. 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. 

PRESENTATION

LIZOLID: Each box contains 3 Blister of 10 Tablets per strip