In Summary

More frequently reported side effects include: anemia, decreased hemoglobin, and thrombocytopenia. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to linezolid: oral powder for suspension, oral tablet

Other dosage forms:

• intravenous solution

Along with its needed effects, linezolid may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking linezolid:

More common

• Chills
• confusion
• dizziness
• fainting
• fast heartbeat
• fever
• lightheadedness
• pale skin
• rapid, shallow breathing
• rash
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

Less common

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• bluish lips or skin
• body aches or pain
• chest pain
• congestion
• constipation
• convulsions
• cough
• decreased urine
• difficult or labored breathing
• dry mouth
• dryness or soreness of the throat
• ear congestion
• headache
• hoarseness
• increased thirst
• irregular heartbeat
• loss of appetite
• loss of voice
• mood changes
• muscle pain or cramps
• nasal congestion
• nausea or vomiting
• not breathing
• numbness or tingling in the hands, feet, or lips
• painful or difficult urination
• pinpoint red spots on the skin
• runny nose
• severe stomach pain
• shortness of breath
• sneezing
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• tender, swollen glands in the neck
• tightness in the chest
• trouble with swallowing
• voice changes
• vomiting of blood or material that looks like coffee grounds
• wheezing

Incidence not known

• Abdominal or stomach discomfort
• blindness
• blistering, peeling, or loosening of the skin
• blurred vision
• burning, numbness, tingling, or painful sensations
• decreased appetite
• decreased vision
• eye pain
• fast, shallow breathing
• general feeling of discomfort
• high fever
• hives
• itching
• joint pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• muscle pain or cramping
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• sleepiness
• swollen glands
• unexplained bleeding or bruising
• unsteadiness or awkwardness
• weakness in the arms, hands, legs, or feet

Some side effects of linezolid may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• bad, unusual, or unpleasant (after) taste
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• change in taste
• discoloration of the tongue
• itching of the vagina or outside genitals
• loose stools
• pain during sexual intercourse
• pain in the arms or legs
• sleeplessness
• sore mouth or tongue
• thick, white curd-like vaginal discharge without odor or with mild odor
• trouble sleeping

Incidence not known

• Discoloration of the tooth

For Healthcare Professionals

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

General

This drug was discontinued due to side effects in up to 3.5% of patients. The most common side effects leading to discontinuation were diarrhea, headache, nausea, and vomiting.

Nervous system

Common (1% to 10%): Headache, dizziness, taste alteration/perversion (metallic taste)

Uncommon (0.1% to 1%): Convulsions, hypoesthesia, paresthesia, tinnitus

Frequency not reported: Drowsiness, seizure, Bell's palsy, sensory loss

Postmarketing reports: Serotonin syndrome (with concomitant serotonergic agents), peripheral neuropathy

Several cases of peripheral and/or optic neuropathy have been reported, mainly when the duration of therapy was longer than 28 days. For example, irreversible sensory loss and peripheral neuropathy were reported in a patient after using this drug for 6 months for actinomycosis. The time from the onset of therapy 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 after this drug was stopped.

At least 15 instances of serotonin syndrome have been reported in patients using this drug with citalopram, sertraline, venlafaxine, fluoxetine, or paroxetine; other concurrent drugs and/or comorbidities may have contributed to the development of serotonin syndrome. The time from the onset of therapy to the first sign of serotonin syndrome averaged 4 days (range: 1 to 20 days) and from the first sign to stopping this drug ranged from 1 to 16 days. Symptoms resolved within 1 to 9 days in 14 patients while 1 patient died suddenly. Three patients died. The first patient developed symptoms 3 weeks after concurrent use of this drug and citalopram. Severe lactic acidosis developed 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 therapy. The patient had cardiopulmonary arrest, then anoxic brain injury, hypertension, tachycardia, and diarrhea, and died in 2 weeks; a similar incident occurred 6 weeks earlier when this drug and sertraline were used. The third patient, who was using citalopram, developed symptoms on day 2 of linezolid therapy and died with cerebral hemorrhage 1 month after the start of serotonin syndrome despite stopping this drug.

A 49-year-old male with multiple comorbidities developed symptoms on day 21 of therapy and was diagnosed with Bell's palsy; symptoms included strange sensation in mouth (no pain, sores, blisters), excessive tearing of left eye, inability to drink properly, left facial frowning, and left-sided facial weakness (involving upper and lower facial muscles). This drug was discontinued and the Bell's palsy completely resolved by day 90. The patient restarted linezolid 5 months later and again showed symptoms on day 21 of therapy. This drug was discontinued and by day 35, the Bell's palsy had practically resolved. The patient had no remaining symptoms 4 months after his second episode.

Convulsions have also been reported during postmarketing experience.

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 C difficile colitis after a long-term course of this drug.

Superficial tooth discoloration and tongue discoloration have also been reported during postmarketing experience.

Common (1% to 10%): Diarrhea, nausea, vomiting, elevated lipase, elevated amylase, tongue discoloration, oral candidiasis, localized abdominal pain, generalized abdominal pain, constipation, dyspepsia

Uncommon (0.1% to 1%): Pancreatitis, gastritis, abdominal distention, dry mouth, glossitis, loose stools, stomatitis, tongue disorder

Rare (0.01% to 0.1%): Antibiotic-associated colitis (including pseudomembranous colitis), superficial tooth discoloration

Frequency not reported: Clostridium difficile-associated diarrhea, lingua villosa nigra, C difficile colitis

Hematologic

Common (1% to 10%): Decreased hemoglobin, decreased platelet count, decreased WBC count, anemia, decreased neutrophils, thrombocytopenia/low platelet count (some requiring platelet transfusions), decreased leukocytes, increased neutrophils, increased eosinophils, decreased hematocrit, decreased RBC count, increased platelet count, increased WBC count

Uncommon (0.1% to 1%): Leukopenia, neutropenia, eosinophilia, increased reticulocyte count

Rare (0.01% to 0.1%): Pancytopenia

Frequency not reported: Red cell hypoplasia, myelotoxicity, bleeding events

Postmarketing reports: Myelosuppression (including anemia, leukopenia, pancytopenia, thrombocytopenia), sideroblastic anemia

Thrombocytopenia (platelets less than 100,000/mm3) has been reported in 32% of patients (n=19) using this drug for more than 10 days. In another study (n=295), thrombocytopenia (platelets less than 150 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% using this drug for more than 5 days. It has been suggested that the mechanism of linezolid-associated thrombocytopenia was immune-mediated.

In a study of patients with linezolid-associated thrombocytopenia, the use of vitamin B6 helped reverse the incidence of thrombocytopenia. Vitamin B6 was most effective when used after this drug was held. Once hematologic levels returned to baseline, coadministration of this drug with vitamin B6 resulted in stable hemoglobin levels for the remainder of therapy.

Another study compared this drug plus 50 mg vitamin B6 per day (n=31) with this drug 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.

Hepatic

Common (1% to 10%): Elevated ALT, elevated AST, abnormal liver function tests

Uncommon (0.1% to 1%): Elevated total bilirubin

Metabolic

Common (1% to 10%): Elevated alkaline phosphatase, elevated LDH, elevated nonfasting glucose

Uncommon (0.1% to 1%): Hyponatremia, decreased nonfasting glucose

Frequency not reported: Hyperlactatemia, metabolic acidosis, hypokalemia

Postmarketing reports: Lactic acidosis, hypoglycemia (including symptomatic episodes)

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

Renal

Common (1% to 10%): Elevated BUN

Uncommon (0.1% to 1%): Elevated creatinine, renal failure

Frequency not reported: Exacerbation of renal failure, abnormal renal function, acute interstitial nephritis

Dermatologic

Common (1% to 10%): Rash, pruritus

Uncommon (0.1% to 1%): Urticaria, dermatitis, diaphoresis

Postmarketing reports: Bullous skin disorders (including severe cutaneous adverse reactions [SCAR] such as Stevens-Johnson syndrome and toxic epidermal necrolysis), angioedema, alopecia

Genitourinary

Common (1% to 10%): Vaginal candidiasis

Uncommon (0.1% to 1%): Vaginitis, polyuria, vulvovaginal disorder

Other

Common (1% to 10%): Fungal infection, candidiasis, fever, localized pain, decreased total protein, decreased albumin, decreased sodium, decreased calcium, increased/decreased potassium, increased/decreased bicarbonate

Uncommon (0.1% to 1%): Chills, fatigue, increased thirst, increased sodium, increased calcium, increased/decreased chloride

Frequency not reported: Generalized edema

Ocular

Partially irreversible bilateral optic neuritis has been reported after 41 weeks of therapy.

Several cases of peripheral and/or optic neuropathy have been reported. The time from the onset of therapy 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 this drug due to optic neuropathy averaged 11 months (range: 1 to 56 months) after therapy initiation. This drug was stopped in 12 cases after the development of optic neuropathy; improvement or complete recovery was observed in all cases.

Uncommon (0.1% to 1%): Blurred vision

Rare (0.01% to 0.1%): Changes in visual field defect

Frequency not reported: Partially irreversible bilateral optic neuritis

Postmarketing reports: Optic neuropathy (sometimes progressing to loss of vision), optic neuritis, loss of vision, changes in visual acuity, changes in color vision

Cardiovascular

Common (1% to 10%): Hypertension

Uncommon (0.1% to 1%): Arrhythmia (tachycardia), transient ischemic attacks, phlebitis, thrombophlebitis

Frequency not reported: Increased and decreased blood pressure, supraventricular tachycardia

Psychiatric

Common (1% to 10%): Insomnia

Frequency not reported: Confusion

Musculoskeletal

Common (1% to 10%): Elevated creatine phosphokinase

Local

Uncommon (0.1% to 1%): Injection site pain

Hypersensitivity

Postmarketing reports: Anaphylaxis

Respiratory

Frequency not reported: Interstitial pneumonia