Linelid Drug Interactions

Linezolid is a weak reversible non-selective inhibitor of monoamine oxidase (MAO). Data on Linezolid interaction and safety in case of prescription to patients with concurrent diseases or taking concomitant drugs, which could put them at risk of MAO inhibiting, are limited. Therefore, under described conditions, use of Linezolid is not recommended, if only there is an opportunity of patient close monitoring.
In normotensive healthy volunteers who received Linezolid, insignificant and transient intensification of pressor effect of Pseudoephedrine hydrochloride or Phenylpropanolamine hydrochloride was observed sometimes. Concomitant use of Linezolid and Pseudoephedrine or Phenylpropanolamine leads to increase in average systolic arterial pressure by 30-40 mmHg, as compared to increase by 11-15 mmHg at use of only Linezolid, by 14-18 mmHg at use of only Pseudoephedrine or Phenylpropanolamine, by 8-11 mmHg at placebo use. The same studies in patients with arterial hypertension were not performed. It is recommended to reduce the initial dose of adrenergic drugs such as dopamine or dopamine agonists, and gradually titrate for achievement of desired clinical response.
Spontaneous reports on cases of serotonin syndrome at concurrent administration of Linezolid and serotonergic agents were very rare.
Antibiotics: Linezolid pharmacokinetics was not changed at concurrent use with Aztreonam or Gentamycin.
Potential interactions between Linezolid and Dextromethorphan were studied in healthy volunteers. They were given Dextromethorphan (two doses of 20 mg prescribed separately in 4 hours) together with Linezolid or without it. In normal individuals, effects of serotonin syndrome (confusion, delirium, irritability, tremor, flushing, hyperhidrosis, hyperpyrexia) were not observed at concurrent administration of Linezolid and Dextromethorphan.
Post-marketing experience: there was one case of development of serotonin syndrome in patient who received Linezolid and Dextromethorphan; it has been solved after discontinuation of both drugs. During clinical use of Linezolid with serotonin reuptake inhibitors, cases of development of serotonin syndrome were rarely reported.
Significant pressor effects were not observed in patients who received Linezolid and less than 100 mg of tyramine. Consequently it is necessary to refrain from use of excessive quantity of food and drinks with high tyramine (hard pressed cheese, yeast extract, undistilled alcoholic drinks, products containing enzymated soybeans, such as soy sauce). Linezolid is not metabolized by human cytochrome P-450 (CYP), and doesn't inhibit any clinically significant human CYP isoforms (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). In the same way, Linezolid doesn't induce P₄₅₀ isoenzymes in animals. Consequently, under Linezolid use, CYP450-induced interactions are not expected.
At addition of Warfarin to therapy with Linezolid, at steady state 10% decrease in average maximum international normalized ratio (INR) was observed in combination with 5% decrease in area under curve concentration-time (AUC). Data from the patients, who received Warfarin and Linezolid, are note enough for assessment of clinical significance of these observations.