Linezolid Side Effects

Some side effects of linezolid may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to linezolid: intravenous solution, oral powder for reconstitution, oral tablet

Get emergency medical help if you have any of these signs of an allergic reaction while taking linezolid: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

If you take an antidepressant or psychiatric medication, call your doctor right away if you have signs of a serious drug interaction, including: confusion, memory problems, feeling hyperactive (mentally or physically), loss of coordination, muscle twitching, shivering, sweating, diarrhea, and/or fever.

Some people develop lactic acidosis while using linezolid. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, slow or uneven heart rate, dizziness, or feeling very weak or tired.

Call your doctor at once if you have any other serious side effects, such as:

• fever, chills, body aches, flu symptoms, sores in your mouth and throat;

• easy bruising or bleeding, pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;

• diarrhea that is watery or bloody;

• blurred vision, trouble seeing color;

• numbness, burning pain, or tingly feeling in your hands or feet;

• seizure (convulsions); or

• low blood sugar (headache, hunger, weakness, sweating, confusion, irritability, dizziness, fast heart rate, or feeling jittery).

Less serious side effects of linezolid may include:

• headache, dizziness, sleep problems (insomnia);

• nausea, vomiting, constipation;

• discolored tongue, unusual or unpleasant taste in the mouth;

• vaginal itching or discharge; or

• yeast infection in the mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to linezolid: intravenous solution, oral powder for reconstitution, oral tablet

General

Linezolid was evaluated in 2046 patients with 85% of adverse events reported as mild to moderate. The most common side effects reported were diarrhea, headache, and nausea.

Gastrointestinal

In cases with known outcome, tooth discoloration was removable with professional dental cleaning (manual descaling).

A 60-year-old man with spondylodiscitis developed a fatal case of Clostridium difficile colitis after a long-term course of linezolid therapy.

Gastrointestinal side effects have included diarrhea (up to 11%), nausea (up to 9.6%), vomiting (3.7%), constipation (2.2%), taste alteration (up to 1.8%), tongue discoloration (up to 1.1%), oral moniliasis (up to 1.1%), dyspepsia, localized abdominal pain, lingua villosa nigra, and pseudomembranous colitis. Superficial tooth discoloration and tongue discoloration have been reported during postmarketing experience.

Hematologic

Hematologic side effects have included decreased hemoglobin (up to 7.1%), platelet count (up to 3%), white blood cells (up to 2.2%), and neutrophils (up to 1.1%). Phase 3 studies have shown a 2.4% incidence of low platelet counts (less than 75% of lower limit of normal) in relation to 1.5% for comparator drugs. Four of these patients required platelet transfusions. Red cell hypoplasia (0.5%) and decreased hemoglobin and hematocrit (4.7%) have also been reported. Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported during postmarketing experience.

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 preexisting myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or those with chronic infection who have received previous or concomitant antibiotic therapy. Discontinuation of therapy should be considered in patients who develop or have worsening myelosuppression.

In one case, linezolid was successfully restarted at a reduced dose after resolution of myelotoxicity.

Thrombocytopenia (platelets less than 100,000/mm3) has been reported in 32% of patients (n=19) receiving linezolid for more than 10 days. In another study (n=295), thrombocytopenia (platelets less than150 x 10(9)/L) occurred in 6.4% of patients and severe thrombocytopenia (platelets less than 50 x 10(9)/L) occurred in 0.3% receiving linezolid for more than 5 days. It has been suggested that the mechanism of linezolid-associated thrombocytopenia is immune-mediated.

In a study of patients with linezolid-associated thrombocytopenia, the administration of vitamin B6 was shown to help reverse the incidence of thrombocytopenia. Vitamin B6 was most effective when it was administered after linezolid treatment was held. Once hematologic levels were returned to baseline, concomitant administration of linezolid and vitamin B6 resulted in stable hemoglobin levels for the remainder of linezolid therapy.

Another study compared linezolid plus 50 mg vitamin B6 per day (n=31) with linezolid alone (n=62) administered to patients with cancer. This study concluded vitamin B6 was not beneficial in the prevention of leukopenia or thrombocytopenia, but found a possible trend towards the prevention of anemia.

Nervous system

Nervous system side effects have included headache (up to 11.3%), insomnia (2.5%), dizziness (up to 2%), drowsiness, confusion, and seizure. At least one case of Bell's palsy has been reported. Serotonin syndrome (in patients receiving concomitant serotonergic agents), convulsions, peripheral neuropathy, and optic neuropathy (sometimes progressing to loss of vision) have been reported during postmarketing experience.

Several cases of peripheral and/or optic neuropathy have been reported, mainly in patients where the duration of therapy was longer than 28 days. For example, irreversible sensory loss and peripheral neuropathy have been reported in a patient after 6 months of linezolid therapy for actinomycosis. The time from the onset of linezolid treatment to the first sign of peripheral neuropathy averaged 4 months (range 10 days to 6 months) in 10 patients with only peripheral neuropathy. In all patients with peripheral neuropathy (n=16), complete recovery was not observed following linezolid discontinuation.

At least 15 instances of serotonin syndrome have been reported in patients receiving linezolid during treatment with citalopram, sertraline, venlafaxine, fluoxetine, or paroxetine. Other concurrent drugs and/or comorbidities may have contributed to the patients developing serotonin syndrome. The time from the onset of linezolid treatment to the first sign of serotonin syndrome averaged 4 days (range 1 to 20 days) and from the first sign to stopping linezolid ranged from 1 to 16 days. The symptoms resolved within 1 to 9 days in 14 patients while one patient died suddenly. Three patients died. The first patient developed symptoms 3 weeks after concurrent treatment with linezolid and citalopram. The patient developed severe lactic acidosis followed by myocardial infarction, and after 3 further episodes of cardiac arrest, the patient died. The second patient stopped sertraline on day 1 and developed symptoms on day 9 of linezolid treatment. The patient had cardiopulmonary arrest, then anoxic brain injury, hypertension, tachycardia, and diarrhea, and died in 2 weeks. This patient had a similar incident 6 weeks earlier when linezolid and sertraline were administered. The third patient, who was receiving citalopram, developed symptoms on day 2 of linezolid treatment and died with cerebral hemorrhage one month following the start of serotonin syndrome despite stopping linezolid.

A 49-year-old male with multiple comorbidities was started on oral linezolid 600 mg twice a day following intravenous vancomycin for the treatment of osteomyelitis. On day 21 of linezolid treatment, the patient reported a strange sensation in his mouth without any pain, sores, or blisters. On day 22, the patient's left eye began to tear inexplicably and he was not able to drink properly. On day 23, left facial frowning and excessive tearing of his left eye was observed on examination. Left-sided facial weakness involving the upper and lower facial muscles was discovered on physical examination. Bell's palsy was diagnosed. Linezolid was discontinued and by day 90, the Bell's palsy completely resolved. Five months later, the patient was restarted on oral linezolid 600 mg twice a day following intravenous vancomycin treatment. On day 21 of linezolid treatment, the patient again developed upper and lower facial muscle weakness on his left side. The linezolid was discontinued and by day 35, the Bell's palsy had practically resolved. Four months following his second episode, the patient had no remaining symptoms.

Metabolic

Metabolic side effects have included lactic acidosis, hyperlactatemia, metabolic acidosis, hyponatremia, and hypokalemia. Elevated lipase (up to 4.3%), alkaline phosphatase (up to 3.5%), amylase (up to 2.4%), LDH (up to 1.8%), and creatine phosphokinase (0.5%) have been reported. Lactic acidosis and hypoglycemia (including symptomatic episodes) have been reported during postmarketing experience.

At least 7 instances of lactic acidosis have been reported following linezolid therapy. The time from the onset of linezolid treatment to the first sign of lactic acidosis ranged from 1 to 16 weeks. Linezolid was stopped within 4 days of identifying lactic acidosis. Two of the 7 patients died despite stopping linezolid. The lactate levels normalized in the 5 surviving patients after stopping linezolid, but one of the patients had sequelae of blindness and disorientation.

Ocular

Several cases of peripheral and/or optic neuropathy have been reported. The time from the onset of linezolid treatment to the first sign of optic neuropathy averaged 10 months (range 1 to 48 months) in 6 patients with only optic neuropathy. The time to discontinuation of linezolid due to optic neuropathy averaged 11 months (range 1 to 56 months) following therapy initiation. Linezolid was stopped in 12 cases following the development of optic neuropathy; improvement or complete recovery was observed in all cases.

Ocular side effects have included optic neuropathy, sometimes in conjunction with peripheral neuropathy after long-term treatment (6 to 10 months). Partially irreversible bilateral optic neuritis has been reported in a patient after 41 weeks of linezolid therapy. Optic neuropathy (sometimes progressing to loss of vision) has also been reported during postmarketing experience.

Dermatologic

Dermatologic side effects have included rash (2%), pruritus, and mild alopecia. Bullous skin disorders (such as those described as Stevens-Johnson syndrome) have been reported during postmarketing experience.

Cardiovascular

Cardiovascular side effects have included increased and decreased blood pressure and supraventricular tachycardia (0.5%).

The potential for hypertensive crisis exists when linezolid is taken concurrently with foods high in tyramine due to the monoamine oxidase inhibiting properties of linezolid.

Genitourinary

Genitourinary side effects have included vaginal moniliasis (up to 1.6%).

Hepatic

Hepatic side effects have included abnormal liver function tests (up to 1.3%). Elevated ALT (up to 9.6%), AST (up to 5%), and total bilirubin (up to 0.9%) have been reported.

Renal

Renal side effects have included exacerbation of renal failure (0.5%) and abnormal renal function. Elevated BUN (up to 2.1%) and creatinine (0.2%) have been reported. Acute interstitial nephritis has been reported.

Other

Other side effects have included fever (1.6%) and generalized edema.

Respiratory

Respiratory side effects have included at least one case of interstitial pneumonia.

Hypersensitivity

Hypersensitivity side effects have included anaphylaxis and angioedema during postmarketing experience.

Immunologic

Immunologic side effects have included fungal infection (up to 1.5%). Superinfection may occur in patients due to overgrowth of resistant organisms.

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