MAOIs Linezolid

Sertraline Linezolid (MAOI effects) Serotonin syndrome... 

Hammemess P, Parada H, Abrams A. Linezolid MAOI activity and potential drug interactions. Psychosomatics (2002) 43,248-9. 

When linezolid is used with antiplatelet drugs such as aspirin or die NSAIDs (see Chap. 18) diere is an increased risk of bleeding and thrombocytopenia When administered widi die MAOIs (see Chap. 31) the effects of the MAOIs are decreased. There is a risk of severe hypertension if linezolid is combined widi large amounts of food containingtyramine (eg, aged cheese, caffeinated beverages, yogurt, chocolate, red wine, beer, pepperoni). 

MAOIs, metoclopramide, phenytoin, sibutramine, smoking, St. John s wort, tramadol, linezolid, L-tryptophan. 

Serotonin syndrome SSRIs, second generation antidepressants, MAOIs, linezolid, tramadol, meperidine, fentanyl, ondansetron, sumatriptan, MDMA, LSD, St. John s wort, ginseng Hypertension, hyperreflexia, tremor, clonus, hyperthermia, hyperactive bowel sounds, diarrhea, mydriasis, agitation, coma onset within hours Sedation (benzodiazepines), paralysis, intubation and ventilation consider 5-HT2 block with cyproheptadine or chlorpromazine... 

The elimination of linezolid is by non-renal means (and does not involve CYP isoenzymes). It has weak MAOI activity. Myelosuppression, both dose- and time-dependent, occurs in 2-10% of patients with therapeutic doses. Linezolid interacts with serotonergic and adrenergic drugs. 

BETA-2 AGONISTS ANTIBIOTICS - LINEZOLID Theoretical risk of hypertensive reactions Linezolid has weak MAOI properties Monitor BP closely during co-administration... 

In an analysis of phase HI 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. A case report describes the serotonin syndrome in an elderly patient treated with linezolid 600 mg every 12 hours, 21 days after amitriptyline 10 mg daily, paroxetine 20 mg daily and alprazolam 500 micrograms daily were started. ... 

Not fully understood. Linezolid has weak MAOI effects, and the serotonin syndrome is known to occur when MAOIs are given with SSRIs , (p.l 142), tricyclics , (p.ll49) and venlafaxine , (p.ll56). In the case of the patient taking linezolid with amitriptyline and paroxetine, it is possible that an interaction between amitriptyline and paroxetine contributed to the development of the serotonin syndrome. Consider also Tricyclic and related antidepressants + SSRIs , p.l241. 

In a study in 14 healthy subjects, two 20-mg doses of dextromethorphan given 4 hours apart, before and during the use of linezolid 600 mg every 12 hours, had no effect on linezolid pharmacokinetics. The AUC and maximum level of the dextromethorphan metabolite, dextrorphan was decreased by 30%, but this was not considered sufficient to warrant any dosing alterations. There was no evidence of the serotonin syndrome, as measured by changes in body temperature, alertness and mental performance. However, the manufacturers describe one case where the concurrent use of linezolid and dextromethorphan resulted in the serotonin syndrome. Linezolid has mild reversible MAOI activity, and the serotonin syndrome has been described when dextromethorphan was taken by patients also taking antidepressant MAOIs, see MAOIs or RIMAs + Dextromethorphan , p.l 134. If the concurrent use of linezolid and dextromethorphan is considered necessary, it would seem prudent to monitor for symptoms of the serotonin syndrome , (p.9). 

Linezolid is a weak, non-selective inhibitor of MAO. As a consequence, it can inhibit the breakdown of the tyramine by MAO in the gut, and can also potentiate the effect of tyramine at nerve endings, therefore causing an increase in blood pressure (see Mechanism, under MAOIs or RIMAs + Tyramine-rich foods , p.ll53). However, the extent of this rise was similar to that for moclobemide, which is much less than that seen with classical MAOIs. 

The manufacturers of linezolid recommend that patients should avoid large amounts of tyramine-rich foods and drinks and should not consume more than 100 mg of tyramine per meal. For a list of the possible tyramine-content of various foods and drinks, see Table 32.2 , (p.ll52), Table 32.3 , (p.ll54) and Table 32.4 , (p.ll55). This is in line with the dietary restrictions recommended for RIMAs rather than the more stringent dietary recommendations required in patients taking non-selective MAOIs. 

The manufacturer of linezolid contraindicates its use with the MAOIs, including the selective MAO-B inhibitor sel line and the RIMA moclobemide. 

The UK manufacturer contraindicates the concurrent use of linezolid with or within 2 weeks of taking any other drug that inhibits MAO-A or MAO-B. They specifically name the non-selective MAOIs isocarboxazid and phenelzine, the RIMA, moclobemide, and the MAO-B inhibitor, selegiline. Linezolid has reversible non-selective MAO-inhibitory activity, and this warning is based on the sometimes serious reactions that have occurred when non-selective MAOIs are given sequentially (see MAOIs + MAOIs or RIMAs , p.1137) or MAOIs are given with MAO-B inhibitors, see MAO-B inhibitors + MAOIs or RIMAs , p.692. 

The UK manufacturer of linezolid (a drug with weak, reversible, non-selective MAOI activity) contraindicates its use with pethidine, unless facilities are available for close observation and monitoring of blood pressure, because of the possibility of serious reactions, as have occurred with classical MAOIs and pethidine, see MAOIs or RIMAs -I- Opioids Pethidine (Meperidine) , p.1140. 

The manufaeturers eontraindieate the use of sympathomimetics (including adrenergic bronchodilators, pseudoephedrine, phenylpropanolamine, adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, dob-utamine) with linezolid unless there are faeilities available for close observation of the patient and monitoring of blood pressure. Some indirectly-aeting sympathomimetics occur in cough and cold remedies, whieh can be bought without prescription. To keep in line with the manufaeturers recommendations, patients should be told to avoid these preparations. However, it should be said that the evidenee available indicates that blood pressure rises are unlikely to be of the proportions seen with the antidepressant MAOIs, which result in hypertensive crises. Consider also MAOIs or RIMAs + Sympathomimetics Indirectly-acting , p.l 147. 

Some other drugs covered elsewhere also have MAOI aetivity. Furazolidone is an antiprotozoal with MAOI activity. Linezolid is an oxazolidi-none antibacterial with reversible nonseleetive MAOI activity. Interactions typical of MAOI inhibitors might therefore occur with furazolidone and linezolid. 

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