In an analysis of phase III studies,changes in vital signs did not differ between patients given linezolid and comparator drugs (i.e. antibiotics) when either were used with drugs known to interact with MAOIs,including unnamed SSRIs (See reference number 1,2). One patient taking fluoxetine had a transient episode of asymptomatic hypertension after one dose of linezolid,but since this patient had no other symptoms of serotonin syndrome, it was not considered an interaction (See reference number 2). However, a 4-year-old girl given fluoxetine 5mg daily developed symptoms of serotonin syndrome 2 days after starting linezolid 140mg every 12 hours, and after a procedure for which she was given fentanyl 200 micrograms. Fentanyl may have been a contributing factor (See reference number 3). Another case report describes an 85-year-old woman taking citalopram who developed tremor,confusion, dysarthria, hyperreflexia, agitation, and restlessness after linezolid was started. Citalopram was stopped and symptoms resolved over 72 hrs (See reference number 4). There are several other case reports of this interaction between linezolid and SSRIs(See reference number 5-8) including citalopram,(See reference number 5,6)sertraline(See reference number 6,7) and paroxetine (See reference number 8,9).
In an analysis of phase III studies,changes in vital signs did not differ between patients given linezolid and comparator drugs (i.e. antibiotics) when either were used with drugs known to interact with MAOIs,including unnamed cyclic antidepressants (See reference number 1,2). A case report describes serotonin syndrome in an elderly patient treated with linezolid 600mg every 12 hours, 21 days after amitriptyline 10mg daily, paroxetine 20mg daily and alprazolam 500 micrograms daily were started (See reference number 9).
Mirtazapine. A patient taking linezolid 600mg twice daily developed delirium,confusion and visual hallucinations 2 weeks after starting to take mirtazapine 15 or 30mg daily and gabapentin 300mg at night. Gabapentin was stopped and delirium resolved. About 4 weeks later delirium recurred and then resolved when patient discontinued mirtazapine. Mirtazapine was restarted without recurrence of delirium. The patient subsequently took mirtazapine 15mg daily with linezolid 600mg twice daily without adverse effects (See reference number 10).
Venlafaxine. An 85-year-old man taking venlafaxine 150mg daily was prescribed ciprofloxacin,rifampicin and linezolid 600mg twice daily for a hip prosthesis infection. After 20 days he was found to be confused and disorientated,and 4 days later he was also drowsy, and suffering myoclonic jerks. Linezolid and venlafaxine were stopped and symptoms resolved over 2 days (See reference number 11). However,another case report describes a 7-year-old boy treated with venlafaxine and methylphenidate who was prescribed linezolid for osteomyelitis. He was given all three drugs (doses not stated) for several days without any alterations in vital signs or evidence of serotonin syndrome (See reference number 12).
Not fully understood. Linezolid has weak MAOI effects, and serotonin syndrome is known to occur when MAOIs are given with SSRIs’, , tricyclics, and venlafaxine, . In case of patient taking linezolid with amitriptyline and paroxetine, it is possible that an interaction between amitriptyline and paroxetine contributed to development of serotonin syndrome. Consider also ‘Tricyclic and related antidepressants + SSRIs.
Information on reaction between linezolid and SSRIs, tricyclics, mirtazapine or venlafaxine appears to be limited, but what is known suggests that interaction is probably rare. The manufacturers of linezolid say that patients taking SSRIs and tricyclic antidepressants should have their blood pressure monitored and be closely observed if given linezolid. They say that if this is not possible,concurrent use should be avoided (See reference number 13). If linezolid is used with a drug with serotonergic actions it would seem prudent to monitor for symptoms of serotonin syndrome, which may take several weeks to manifest. See The serotonin syndrome,, for further details.
1.
Hartman CS,Leach TS, Todd WM, Hafkin B. Lack of drug-interaction with combination oflinezolid and monoamine oxidase inhibitor-interacting medications. Pharmacotherapy (2000) 20, 1230.
2.
Rubinstein E,Isturiz R, Standiford HC, Smith LG, Oliphant TH, Cammarata S, Hafkin B, LeV, Remington J. Worldwide assessment of linezolid’s clinical safety and tolerability: comparator-controlled phase III studies. Antimicrob Agents Chemother (2003) 47, 1824–31.
3.
Thomas CR,Rosenberg M, Blythe V, Meyer WJ. Serotonin syndrome and linezolid. J Am Acad Child Adolesc Psychiatry (2004) 43, 790.
4.
Tahir N. Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram. J Am Med Dir Assoc (2004) 5,111–13.
5.
Bernard L,Stern R, Lew D, Hoffmeyer P. Serotonin syndrome after concomitant treatmentwith linezolid and citalopram. Clin Infect Dis (2003) 36, 1197.
6.
Hachem RY,Hicks K, Huen A, Raad I. Myelosuppression and serotonin syndrome associatedwith concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrowtransplant recipients. Clin Infect Dis (2003) 37, 37: e8–e11.
7.
Lavery S,Ravi H, McDaniel WW, Pushkin YR. Linezolid and serotonin syndrome. Psychosomatics (2001) 42, 432–4.
8.
Wigen CL,Goetz MB. Serotonin syndrome and linezolid. Clin Infect Dis (2002) 34, 1651–2.
9.
Morales-Molina JA,Mateu-de Antonio J, Grau Cerrato S, Marín-Casino M. Probable síndrome serotoninérgico por interacción entre amitriptilina, paroxetina y linezolid. Farm Hosp (2005) 29, 1–2.
Aga VM,Barklage NE, Jefferson JW. Linezolid, a monoamine oxidase inhibiting antibiotic,and antidepressants. J Clin Psychiatry (2003) 64, 609–11.
Jones SL,Athan E, O’Brien D. Serotonin syndrome due to co-administration of linezolid andvenlafaxine. J Antimicrob Chemother (2004) 54, 289–90.
Hammerness P,Parada H, Abrams A. Linezolid: MAOI activity and potential drug interactions. Psychosomatics (2002) 43, 248–9.
Zyvox (Linezolid). Pharmacia Ltd. UK Summary of product characteristics,July 2007.