ZYVOX

What it is

ZYVOX is a film-coated tablet containing 600 mg of linezolid. Linezolid is a synthetic antibacterial agent belonging to the oxazolidinones class, which selectively inhibits bacterial protein synthesis via a mechanism of action different from that of other antibacterial agents. ZYVOX is active against Gram-positive bacteria only and has no clinical activity against Gram-negative pathogens.

Approved indications

— Treatment of suspected or proven infections due to Gram-positive organisms resistant to multiple classes of antibiotics, including methicillin-resistant *Staphylococcus* species and vancomycin resistant *Enterococcus* species.

Dosing overview

For adults and children 12 years or older, the recommended dosage is administered orally twice daily. Community-acquired pneumonia and nosocomial pneumonia are treated with 600 mg, skin and soft tissue infections with 400 mg to 600 mg depending on clinical severity, and Enterococcal infections with 600 mg, for durations ranging from 10 to 28 consecutive days depending on the infection type. ZYVOX is administered orally with or without food. No dose adjustment is required in the elderly, in patients with impaired hepatic function or impaired renal function.

Key safety warnings

Myelosuppression (including anaemia, leucopenia, pancytopenia and thrombocytopenia) has been reported in patients receiving linezolid. In cases where the outcome is known, the affected haematological parameters have risen towards pre-treatment levels when linezolid was discontinued. Complete blood counts should be monitored weekly in patients who receive linezolid for longer than two weeks, particularly those with pre-existing myelosuppression, who have severe renal insufficiency or moderate to severe hepatic impairment, those receiving concomitant drugs that produce bone marrow suppression, or may decrease haemoglobin levels or platelet count or function, or those with a chronic infection who have received previous antibiotic therapy. Peripheral neuropathy and optic neuropathy have been reported in patients treated with linezolid, primarily those patients treated for longer than the maximum recommended duration of 28 days. In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration. If symptoms of visual impairment appear, such as changes in visual acuity, changes in colour vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended. Visual function should be monitored in all patients taking linezolid for extended periods (greater than or equal to 3 months) and in all patients reporting new visual symptoms regardless of length of therapy with linezolid. Lactic acidosis has been reported with the use of linezolid. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate level while receiving linezolid should receive immediate medical attention. Serotonin syndrome has been reported in association with the coadministration of linezolid and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and opioids. Rhabdomyolysis has been reported with the use of linezolid. If signs or symptoms of rhabdomyolysis are observed, linezolid should be discontinued and appropriate therapy initiated.

Contraindications

ZYVOX is contraindicated in patients with hypersensitivity to linezolid or to any of the excipients in the tablet. Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (such as phenelzine) or within two weeks of taking any such medicinal product. Unless patients are monitored for potential increases in blood pressure, linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking directly and indirectly acting sympathomimetic agents (such as pseudoephedrine), vasopressive agents (such as adrenaline or noradrenaline), or dopaminergic agents (such as dopamine or dobutamine). Unless patients are carefully observed for signs and/or symptoms of serotonin syndrome, linezolid should not be administered to patients with carcinoid syndrome and/or patients taking serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), pethidine or buspirone.

Regulatory history

ZYVOX linezolid 600 mg tablets were first listed on the ARTG on 24 September 2001.