Drug interactions between linezolid and Sudafed PE Cold & Cough

phenylephrine ↔ linezolid

Applies to:Sudafed PE Cold & Cough (acetaminophen/dextromethorphan/guaifenesin/phenylephrine) and linezolid

CONTRAINDICATED: Linezolid may potentiate the pressor response to sympathomimetic agents. Linezolid is a reversible, nonselective monoamine oxidase inhibitor (MAOI) and, as such, may enhance sympathomimetic effect by increasing norepinephrine storage in adrenergic neurons. The interaction may be more likely to occur with indirect- or mixed-acting sympathomimetics such as pseudoephedrine or ephedrine than with direct-acting agents like epinephrine, norepinephrine, and isoproterenol. In healthy normotensive subjects, coadministration of linezolid (600 mg every 12 hours for 3 days) and two doses of pseudoephedrine (60 mg each) or phenylpropanolamine (25 mg each) given 4 hours apart resulted in a mean maximum increase in systolic blood pressure of 32 mmHg and 38 mmHg, respectively, compared to baseline. The mean maximum systolic blood pressure during coadministration was also significantly increased compared to either agent alone. Heart rate was not affected. Maximum blood pressure levels were seen 2 to 3 hours after the second dose of phenylpropanolamine or pseudoephedrine, and returned to baseline 2 to 3 hours after peak.

MANAGEMENT: Unless blood pressure and clinical status can be closely monitored, linezolid should not be administered in combination with direct- or indirect-acting sympathomimetic agents (e.g., pseudoephedrine, phenylpropanolamine), vasopressive agents (e.g., epinephrine, norepinephrine), or dopaminergic agents (e.g., dopamine, dobutamine). If the combination is used, lower initial dosages of adrenergic agents such as dopamine or epinephrine are recommended, with careful titration to the desired response.

dextromethorphan ↔ linezolid

Applies to:Sudafed PE Cold & Cough (acetaminophen/dextromethorphan/guaifenesin/phenylephrine) and linezolid

Linezolid may reduce the conversion of dextromethorphan to its primary metabolite, dextrorphan. The clinical significance and mechanism of interaction are unknown. In 14 healthy volunteers, coadministration of linezolid (600 mg orally every 12 hours for 6 days) and dextromethorphan (20 mg orally twice, 4 hours apart, on days 4 and 6 of linezolid administration) resulted in an approximately 30% decrease in both the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of dextrorphan compared to administration of dextromethorphan alone. No effect on the pharmacokinetics of linezolid were observed. Pharmacodynamically, use of this combination may potentiate the risk of the serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5HT1A receptors and characterized by CNS irritability, altered consciousness, confusion, myoclonus, ataxia, abdominal cramping, hyperpyrexia, shivering, pupillary dilation, diaphoresis, hypertension, and tachycardia. In terms of drug interaction, the serotonin syndrome has been reported most often during coadministration of drugs that inhibit monoamine oxidase-A (the enzyme involved in serotonin metabolism) and those that inhibit serotonin reuptake. Since linezolid is a weak monoamine oxidase-A inhibitor and dextromethorphan is a serotonin reuptake inhibitor, the interaction could conceivably occur. In clinical practice, use of linezolid with selective serotonin reuptake inhibitors and use of dextromethorphan with MAOI antidepressants have been associated with development of the serotonin syndrome. However, in the study, no changes in mental status (sedation, performance testing) or autonomic function (blood pressure, heart rate, body temperature) were observed during combination therapy relative to either linezolid or dextromethorphan alone. The investigators concluded that linezolid may be prescribed with dextromethorphan without restrictions.