linezolid: clinical use

Prescribing considerations

• Initiate in a hospital environment after microbiology or infectious-diseases consultation.
• Base use on microbiology, susceptibility and local resistance information.
• Linezolid lacks dependable Gram-negative activity; provide appropriate additional cover when Gram-negative infection is suspected or confirmed.
• Review all serotonergic, adrenergic, vasopressor, dopaminergic and over-the-counter medicines before initiation.
• Use particular caution with prolonged exposure, pre-existing cytopenias, severe renal impairment, moderate-to-severe hepatic impairment and medicines affecting blood counts or platelet function.

Contraindications and cautions

• Hypersensitivity to linezolid or formulation excipients.
• Current use of a monoamine oxidase A or B inhibitor, or use within the preceding two weeks.
• Without facilities for close observation and blood-pressure monitoring: specified conditions such as uncontrolled hypertension, phaeochromocytoma, carcinoid syndrome or thyrotoxicosis, and specified serotonergic or sympathomimetic combinations.
• Breastfeeding should be discontinued before and throughout administration under the selected product information.
• The oral suspension is unsuitable for certain hereditary sugar-intolerance disorders and requires consideration in phenylketonuria because it contains aspartame.

Monitoring

• Obtain complete blood counts regularly; the SmPC recommends weekly monitoring during treatment.
• Monitor more closely where cytopenia risk is increased, including severe renal or significant hepatic impairment.
• Assess any new visual symptoms promptly; monitor visual function during prolonged treatment.
• Ask about peripheral neuropathy, severe diarrhoea, serotonin toxicity and symptoms of lactic acidosis.
• Monitor blood pressure when clinically relevant interacting medicines cannot be avoided.
• Consider serum sodium monitoring in patients at risk of hyponatraemia.

Clinical pharmacology

Linezolid is an oxazolidinone that inhibits bacterial protein synthesis by binding 23S ribosomal RNA within the 50S subunit and preventing formation of the functional 70S initiation complex. Oral bioavailability is approximately complete, supporting clinically appropriate switching between intravenous and oral formulations. It is a reversible, non-selective monoamine oxidase inhibitor and is not detectably metabolised through the cytochrome P450 system.

Formulation and product differences

• Film-coated tablets contain lactose.
• The reconstituted orange-flavoured suspension contains sucrose, mannitol, sorbitol, fructose, aspartame and sodium benzoate; gently invert before use rather than shaking.
• The ready-to-use infusion contains glucose and sodium, must not receive additives and has documented physical or chemical incompatibilities with several intravenous medicines.
• Oral and intravenous formulations provide similar systemic availability, allowing formulation changes when clinically appropriate.

Solution for infusion

Route: Intravenous

Strengths: 2 mg/mL

Oral suspension

Route: Oral

Strengths: 100 mg/5 mL

Tablet

Route: Oral

Strengths: 600 mg