Linezolid - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Myelosuppression: Monitor complete blood counts weekly.

Thrombocytopenia has been reported more often in patients with severe renal and in patients with moderate to severe hepatic impairment.

Consider discontinuation in patients who develop or have worsening myelosuppression. • Peripheral and Optic Neuropathy: Reported primarily in patients treated for longer than 28 days.

If patients experience symptoms of visual impairment, prompt ophthalmic evaluation is recommended. • Serotonin Syndrome: Monitor patients taking serotonergic agents, including antidepressants and opioids, for signs of serotonin syndrome.

Patients taking serotonergic antidepressants should receive linezolid only if no other therapies are available.

Discontinue serotonergic antidepressants and monitor patients for signs and symptoms of both serotonin syndrome and antidepressant discontinuation. • A mortality imbalance was seen in an investigational study in linezolid-treated patients with catheter-related bloodstream infections. • Clostridioides difficile- Associated Diarrhea: Evaluate if diarrhea occurs. • Potential interactions producing elevation of blood pressure: monitor blood pressure. • Rhabdomyolysis: If signs or symptoms of rhabdomyolysis are observed, discontinue Linezolid Tablets and initiate appropriate therapy. • Hypoglycemia: Postmarketing cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents. • Hyponatremia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): Monitor serum sodium levels regularly in patients at risk of hyponatremia and/or SIADH.

5.1 Myelosuppression Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving linezolid.

In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment levels.

Thrombocytopenia has been reported more often in patients with severe renal impairment, whether or not on dialysis, and in patients with moderate to severe hepatic impairment.

Complete blood counts should be monitored weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than two weeks, those with pre-existing myelosuppression, those with severe renal impairment or moderate to severe hepatic impairment, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibacterial drug therapy.

Discontinuation of therapy with linezolid should be considered in patients who develop or have worsening myelosuppression [ see Adverse Reactions ] .

5.2 Peripheral and Optic Neuropathy Peripheral and optic neuropathies have been reported in patients treated with linezolid, primarily in those patients treated for longer than the maximum recommended duration of 28 days.

In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration.

Visual blurring has been reported in some patients treated with linezolid for less than 28 days.

Peripheral and optic neuropathy has also been reported in children.

If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended.

Visual function should be monitored in all patients taking linezolid for extended periods (≥ 3 months) and in all patients reporting new visual symptoms regardless of length of therapy with linezolid.

If peripheral or optic neuropathy occurs, the continued use of linezolid in these patients should be weighed against the potential risks.

5.3 Serotonin Syndrome Spontaneous reports of serotonin syndrome including fatal cases associated with the co-administration of linezolid and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported.

Unless clinically appropriate and patients are carefully observed for signs and/or symptoms of serotonin syndrome or neuroleptic malignant syndrome-like (NMS-like) reactions, linezolid should not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, bupropion, buspirone, serotonin 5-HT1 receptor agonists (triptans), and opioids, including meperidine [ see Drug Interactions and Clinical Pharmacology ].

In some cases, a patient already receiving a serotonergic antidepressant or buspirone may require urgent treatment with linezolid.

If alternatives to linezolid are not available and the potential benefits of linezolid outweigh the risks of serotonin syndrome or NMS-like reactions, the serotonergic antidepressant should be stopped promptly and linezolid administered.

The patient should be monitored for two weeks (five weeks if fluoxetine was taken) or until 24 hours after the last dose of linezolid, whichever comes first.

Symptoms of serotonin syndrome or NMS-like reactions include hyperthermia, rigidity, myoclonus, autonomic instability, and mental status changes that include extreme agitation progressing to delirium and coma.

The patient should also be monitored for discontinuation symptoms of the antidepressant (see package insert of the specified agent(s) for a description of the associated discontinuation symptoms).