Table 2.
Summary of adverse events associated with linezolid treatment
| Description | Comments |
|---|---|
| Minor reactions | |
| Include diarrhea, nausea, headache, taste disturbances, dizziness | Minor side-effects seen more commonly in phase III trials than with comparator drugs.129 |
| Allergic reactions | |
| Immediate hypersensitivity | Reaction after 1st dose of linezolid.132 |
| Delayed hypersensitivity | Purpuric rash reported on day of 9 linezolid.133 |
| Interstitial nephritis | Esposito et al.135 |
| DRESS syndrome | Developed after day 7 of linezolid.136 |
| Lactic acidosis | |
| Increased blood lactate levels (>4–5 mmol/L) with metabolic acidosis | Usually associated with prolonged linezolid treatment and resolves when linezolid is stopped. Linezolid thought to cause lactic acidosis via inhibition of mitochondrial protein synthesis. Some patients more susceptible due to polymorphisms in mitochondrial DNA. |
| Hematological | |
| Myelosuppresion | Effects are mainly on red cell and platelet lineages, usually moderate, reversible and dose-dependent in case reports and phase I trials.144 Conflicting results from CCTs and meta-analyses; some suggest increased incidence of hematological side-effects compared to comparator drugs,149 others suggesting no significant difference.147 |
| Thrombocytopenia | Commonest reported hematological side-effect.92 Some reports suggest related to length of treatment.146 Reports of more severe thrombocytopenia developing in patients with impaired renal function154 possibly due to impaired renal clearance155 and higher linezolid AUC.156 Has been used in HSCT patients without delaying platelet engraftment (Cohen et al157). |
| Anemia | Marrow appearances suggest anemia occurs due to bone marrow suppression (Bernstein et al150). A transient delay in neutrophil recovery was reported in oncology patients with baseline marrow suppression (Jaksic et al123) but it was not reflected in length of antibiotic treatment required. Has been used in HSCT patients without delaying neutrophil engraftment.157 |
| Pure red cell aplasia | 1 case report after 8 weeks linezolid.145 |
| Hepatic dysfunction | |
| Raised transaminases | Meta-analysis of 7 comparator controlled trials found mean transaminase levels stayed within normal range during treatment, and no significant difference in transaminases in patients receiving comparator drug.129 |
| Microvesicular steatosis | Case report in a patient on prolonged linezolid treatment.158 |
| Neurological toxicity | |
| Peripheral neuropathy | Usually presents as parasthesia with sensory loss, often painful. May be irreversible or take months to recover.160,161 |
| Optic neuropathy | Presents with acute LOV, loss of colour vision and visual acuity. Recovery occurs more often than peripheral neuropathy does.162 Both types may co-exist and usually occur after prolonged treatment.159 |
| Bell’s Palsy | Case report.165 |
| Cardiac | |
| QTc interval | No effect in phase I studies.129 |
| Pregnancy | No controlled studies performed. |
| Drug interactions | |
| Serotonin syndrome | Potential interaction with serotinergic and adrenergic drugs because linezolid is a mild MAOI. Several case reports of SS when co-administered with SSRIs. A retrospective review of patients concluded linezolid and SSRIs may be taken concomitantly if monitored for development of SS.171 Review of data from phase III and IV CCTs found no increased risk of SS in patients on linezolid or comparator.170 |
| Cytochrome p450 interactions | Linezolid is not an inhibitor or substrate of p450.165 |
Abbreviations: DRESS, drug rash with eosinophilia and systemic symptoms; LOV, loss of vision; MAOI, monoamine oxidase inhibitor; CCTs, comparator controlled trials; SS, serotonin syndrome; SSRI, selective serotonin re-uptake inhibitors; AUC, area under the time-concentration curve; HSCT, hemopoeitic stem cell transplant.