In Summary

More frequently reported side effects include: diarrhea and insomnia. See below for a comprehensive list of adverse effects.

WARNINGS: Levofloxacin may rarely cause tendon damage (such as tendinitis, tendon rupture) during or after treatment. Your risk for tendon problems is greater if you are over 60 years of age, if you are taking corticosteroids (such as prednisone), or if you have had a kidney, heart or lung transplant. Stop exercising, rest, and get medical help right away if you develop joint/muscle/tendon pain or swelling.

Levofloxacin should not be used in patients with myasthenia gravis. It may cause the condition to become worse. Seek immediate medical attention if you develop muscle weakness or trouble breathing.

For the Consumer

Applies to levofloxacin: oral solution, oral tablet

Other dosage forms:

• intravenous solution

Along with its needed effects, levofloxacin 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 levofloxacin:

More common

• Diarrhea

Rare

• Agitation
• blisters
• confusion
• diarrhea (watery and severe) which may also be bloody
• feeling that others can hear your thoughts or control your behavior
• fever
• pain, inflammation, or swelling in the calves of the legs, shoulders, or hands, including tendon rupture or swelling of the tendon (tendinitis)
• redness and swelling of the skin
• seeing, hearing, or feeling things that are not there
• sensation of burning on the skin
• severe mood or mental changes
• stomach cramps or pain (severe)
• skin rash, itching, or redness
• trembling
• unusual behavior

Incidence not known

• Black, tarry stools
• blurred vision
• burning, numbness, tingling, or painful sensation including peripheral neuropathy.
• cough
• dark urine
• difficulty with breathing
• difficulty with chewing, talking, or swallowing
• drooping eyelids
• fainting
• fast or irregular heartbeat
• general body swelling
• hives
• hoarseness
• joint or muscle pain including tendon rupture or swelling of the tendon (tendinitis).
• muscle cramps, spasms, pain, or stiffness
• peeling or loosening of the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• seizures
• severe dizziness
• severe tiredness
• tightness in the chest
• unsteadiness or awkwardness
• unusual bleeding or bruising
• unusual tiredness or weakness
• vision changes
• voice changes
• weakness in the arms, hands, legs, or feet including worsening of myasthenia gravis.

Some side effects of levofloxacin 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

• Change in taste
• constipation
• dizziness
• drowsiness
• headache
• lightheadedness
• nausea
• nervousness
• stomach pain or discomfort
• trouble sleeping
• vaginal itching and discharge
• vomiting

Incidence not known

• Feeling of warmth or heat
• flushing or redness of the skin, especially on the face and neck
• sweating

For Healthcare Professionals

Applies to levofloxacin: compounding powder, intravenous solution, oral solution, oral tablet

General

The most frequently reported side effects with the IV and oral formulations included nausea, headache, diarrhea, insomnia, constipation, and dizziness. Therapy was discontinued due to side effects in 4.3% of patients overall (3.8% treated with 250 mg and 500 mg doses; 5.4% treated with 750 mg dose). The most common side effects leading to discontinuation were gastrointestinal (primarily nausea, vomiting), dizziness, and headache.

Cough/productive cough, dysgeusia, and fatigue/asthenia were reported most often with the nebulizer solution formulation.

Gastrointestinal

During 1 study, C difficile-associated diarrhea occurred in 11 of 490 study patients (2.2%) receiving this drug.

Hemorrhagic diarrhea has been reported, which in very rare cases was indicative of enterocolitis (including pseudomembranous colitis).

Common (1% to 10%): Nausea, diarrhea, constipation, abdominal pain, dyspepsia, vomiting

Uncommon (0.1% to 1%): Gastroenteritis, pancreatitis, glossitis, gastritis, esophagitis, flatulence, stomatitis, pseudomembranous/Clostridium difficile colitis

Frequency not reported: Dry mouth, dysphagia, gastrointestinal hemorrhage, tongue edema, gastroesophageal reflux, melena, taste perversion, intestinal perforation, intestinal obstruction, C difficile-associated diarrhea, hemorrhagic diarrhea, enterocolitis

Nebulizer Solution:

-Common (1% to 10%): Nausea, vomiting, abdominal pain, diarrhea, constipation

-Uncommon (0.1% to 1%): Retching, dyspepsia, flatulence, oral fungal infection

Nervous system

Common (1% to 10%): Headache, dizziness

Uncommon (0.1% to 1%): Convulsions, hyperkinesias, hypertonia, paresthesia, somnolence, tremor, vertigo, abnormal gait, syncope, dysgeusia

Rare (0.01% to 0.1%): Tinnitus

Frequency not reported: Abnormal coordination, coma, hypoesthesia, dysesthesia, weakness, involuntary muscle contractions, hyperesthesia, paralysis, speech disorder, stupor, encephalopathy, leg cramps, ataxia, migraine, seizures, benign intracranial hypertension, hearing loss, hearing impaired, peripheral sensory neuropathy/sensory axonal polyneuropathy, peripheral sensory motor neuropathy/sensorimotor axonal polyneuropathy, dyskinesia, extrapyramidal disorder, hypoglycemic coma

Postmarketing reports: Abnormal electroencephalogram (EEG), exacerbation of myasthenia gravis, anosmia, ageusia, parosmia, encephalopathy (isolated reports), pseudotumor cerebri, hypoacusis, peripheral neuropathy (sometimes irreversible)

Nebulizer Solution:

-Very common (10% or more): Dysgeusia (30%)

-Common (1% to 10%): Headache, dizziness, tinnitus

-Uncommon (0.1% to 1%): Hyposmia, somnolence, hearing loss

Cases of sensory or sensorimotor axonal polyneuropathy (affecting small and/or large axons) resulting in paresthesias, hypoesthesias, dysesthesias, and weakness have been reported.

One survey reported 33 cases of peripheral neuropathy associated with this drug, ranging in severity from mild and reversible to severe and persistent. In 1 case, a 51-year-old female developed "electrical" sensations, numbness, allodynia, multiple severe tendinitis, partial tendon rupture, impaired memory, confusion, and impaired concentration, with some symptoms persisting after 1 year.

Psychiatric

Attempted or completed suicide reported, especially in patients with medical history of/underlying risk factor for depression.

Common (1% to 10%): Insomnia

Uncommon (0.1% to 1%): Abnormal dreams, agitation, anxiety, confusional state, nervousness, depression, hallucination, nightmare, sleep disorder

Rare (0.01% to 0.1%): Psychotic reactions (with hallucination, paranoia)

Frequency not reported: Aggressive reaction, delirium, emotional lability, impaired concentration, manic reaction, mental deficiency, toxic psychoses, withdrawal syndrome, psychotic disorders/reactions with self-endangering behavior (including suicidal ideation, suicide attempt)

Postmarketing reports: Psychosis, paranoia, suicide attempt (isolated reports), suicidal ideation (isolated reports), completed suicide (isolated reports)

Nebulizer Solution:

-Common (1% to 10%): Insomnia

-Uncommon (0.1% to 1%): Anxiety, depression

Dermatologic

Mucocutaneous reactions have been reported, sometimes after the first dose.

A 78-year-old female developed toxic epidermal necrolysis 2 days after parenteral therapy. The rash initially manifested as an erythematous rash, blistering, and mucosal sloughing but progressed to exfoliation involving three-quarters of the patient's body surface area including mucosa. A positive Nikolsky sign was noted.

A 15-year-old male developed fatal toxic epidermal necrolysis taking this drug for 9 days. The rash progressed over 40 hours to involve 80% of his body surface area with a positive Nikolsky sign and involvement of the eyes and oral, nasal, and perianal mucosa.

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

Uncommon (0.1% to 1%): Urticaria, hyperhidrosis

Rare (0.01% to 0.1%): Angioedema

Frequency not reported: Dry skin, skin disorder, skin exfoliation, skin ulceration, erythematous rash, alopecia, maculopapular rash, erythema nodosum, eczema, mucocutaneous reactions

Postmarketing reports: Photosensitivity/phototoxicity reaction, bullous eruptions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, fixed drug eruptions, erythema multiforme), leukocytoclastic vasculitis

Nebulizer Solution:

-Common (1% to 10%): Rash

-Uncommon (0.1% to 1%): Urticaria, pruritus

Musculoskeletal

Achilles tendon rupture occurred in 4 of 489 study patients (3217 treatment days) after 1 to 10 days of this drug.

Severe rhabdomyolysis occurred in a 77-year-old female after 6 days of oral therapy. She developed acute renal failure (serum creatinine 678 micromole/L), hyperkalemia (6.8 micromole/L), anuria, elevated creatine kinase (30,400 international units/L), myoglobinemia (86,000 mcg/L), and acute hepatic cytolysis (AST 555 international units/L, ALT 249 international units/L). The fluid/electrolyte disorders and creatine kinase and myoglobin levels improved with hemodialysis; however, the patient died of a myocardial infarction and respiratory failure after 13 days.

Uncommon (0.1% to 1%): Arthralgia, myalgia, skeletal pain, tendinitis

Rare (0.01% to 0.1%): Tendon disorders (including tendinitis [e.g., Achilles tendon]), muscular weakness

Frequency not reported: Arthritis, arthrosis, pathological fracture, osteomyelitis, synovitis , back pain, ligament rupture

Postmarketing reports: Tendon rupture (e.g., Achilles tendon), muscle injury (including rupture), increased muscle enzymes, rhabdomyolysis

Nebulizer Solution:

-Common (1% to 10%): Arthralgia, myalgia

-Uncommon (0.1% to 1%): Tendinitis, costochondritis, joint stiffness

Cardiovascular

Ventricular arrhythmia and torsade de pointes have been reported, mainly in patients with risk factors of QT prolongation.

This drug was associated with 13 cases of torsade de pointes reported to the FDA between 1996 and 2001.

An 88-year-old woman developed a prolonged QTc interval during treatment with this drug (500 mg once a day). The QTc interval increased from 450 msec to 577 msec by the fourth day of treatment. This drug was discontinued after the patient experienced runs of ventricular tachycardia. The QTc interval then decreased to 437 msec 2 days after discontinuing this drug.

A 65-year-old woman with hypokalemia (2.8 mEq/L), hypomagnesemia (1.5 mEq/L), and renal insufficiency (serum creatinine 7.7 mg/dL, BUN 34 mg/dL) developed a QTc interval of 605 ms (baseline 435 to 485 ms), several episodes of torsade de pointes, and cardiac arrest after 3 days of this drug (250 mg/day IV). The QTc interval decreased to 399 ms and no further arrhythmias occurred after discontinuation of this drug and electrolyte replacement.

Hypotension has been associated with rapid or bolus IV infusion.

Common (1% to 10%): Phlebitis

Uncommon (0.1% to 1%): Cardiac arrest, palpitation, ventricular arrhythmia, ventricular tachycardia

Rare (0.01% to 0.1%): Tachycardia, hypotension

Frequency not reported: Angina pectoris, arrhythmia, atrial fibrillation, bradycardia, cardiac failure, cerebrovascular disorder, circulatory failure, coronary thrombosis, heart block, hypertension, aggravated hypertension, myocardial infarction, postural hypotension, purpura, supraventricular tachycardia, deep thrombophlebitis, vasculitis, ventricular fibrillation

Postmarketing reports: Vasodilation, QT interval prolongation/prolonged ECG QT, torsade de pointes

Nebulizer Solution:

-Uncommon (0.1% to 1%): Tachycardia, prolonged ECG QT

Other

Decreased weight was reported during clinical trials for the nebulizer solution, but was primarily considered disease-related rather than drug-related.

Common (1% to 10%): Chest pain, edema, moniliasis

Uncommon (0.1% to 1%): Asthenia, increased alkaline phosphatase, fungal infection (including Candida infection), pathogen resistance

Rare (0.01% to 0.1%): Pyrexia

Frequency not reported: Malaise, increased LDH, elevated serum triglycerides, elevated serum cholesterol, rigors, substernal chest pain, ascites, changed temperature sensation, ear disorder (unspecified), enlarged abdomen, hot flashes, gangrene, influenza-like symptoms, leg pain, multiple organ failure, earache, abscess, herpes simplex, bacterial infection, viral infection, otitis media, sepsis, pain (including pain in back, chest, extremities), fatigue, face edema, flushing, aggravated condition

Postmarketing reports: Multi-organ failure

Nebulizer Solution:

-Very common (10% or more): Fatigue/asthenia (25%), decreased exercise tolerance, decreased weight

-Common (1% to 10%): Pyrexia

-Uncommon (0.1% to 1%): Increased blood alkaline phosphatase

Hepatic

Common (1% to 10%): Increased hepatic enzymes (ALT/AST, alkaline phosphatase, GGT)

Uncommon (0.1% to 1%): Abnormal hepatic function, increased blood bilirubin

Frequency not reported: Acute hepatocellular injury, cholecystitis, cholelithiasis, hepatic coma, hepatic necrosis, bilirubinemia, severe liver injury (including fatal cases with acute liver failure)

Postmarketing reports: Severe hepatotoxicity (including acute hepatitis and fatal events), hepatic failure (including fatal cases), hepatitis, jaundice

Nebulizer Solution:

-Common (1% to 10%): Increased ALT, increased AST

-Uncommon (0.1% to 1%): Hepatitis, hyperbilirubinemia, abnormal liver function test

Severe liver injury (including fatal cases with acute liver failure) has been reported, primarily in patients with severe underlying diseases.

A 74-year-old female developed hepatotoxicity and significantly increased AST (4962 units/L), ALT (7071 units/L), alkaline phosphatase (90 units/L), and total bilirubin (2.5 mg/dL) after starting this drug. Levels returned to normal within a week after discontinuation.

Severe hepatotoxicity usually occurred within 14 days (most within 6 days) after starting this drug and most cases were not associated with hypersensitivity. The majority of fatal hepatotoxicity cases occurred in patients 65 years or older and most were not associated with hypersensitivity.

Hypersensitivity

Uncommon (0.1% to 1%): Allergic reaction

Rare (0.01% to 0.1%): Hypersensitivity

Postmarketing reports: Hypersensitivity reactions (sometimes fatal and including anaphylactic/anaphylactoid reactions, anaphylactic/anaphylactoid shock, serum sickness, angioneurotic edema)

Nebulizer Solution:

-Uncommon (0.1% to 1%): Hypersensitivity

Anaphylactic and anaphylactoid reactions have been reported, sometimes after the first dose.

Respiratory

Common (1% to 10%): Dyspnea

Uncommon (0.1% to 1%): Epistaxis

Frequency not reported: Rhinitis, sinusitis, pharyngitis, bronchitis, chronic obstructive airway disease, laryngitis, pleurisy, pneumonitis, upper respiratory tract infection, asthma, cough, hemoptysis, hiccough, hypoxia, pleural effusion, pulmonary embolism, respiratory insufficiency, airway obstruction, acute respiratory distress syndrome, aspiration, bronchospasm, emphysema, pneumonia, pneumothorax, pulmonary collapse, pulmonary edema, respiratory depression, respiratory disorder

Postmarketing reports: Allergic pneumonitis (isolated reports), dysphonia

Nebulizer Solution:

-Very common (10% or more): Cough/productive cough (54%), dyspnea, changes in bronchial secretions (volume, viscosity), hemoptysis, decreased forced expiratory volume

-Common (1% to 10%): Dysphonia, decreased pulmonary function test, abnormal breath sounds

-Uncommon (0.1% to 1%): Bronchospasm, bronchial hyper-reactivity, obstructive airways disorder

Hematologic

Uncommon (0.1% to 1%): Anemia, granulocytopenia, thrombocytopenia, eosinophilia, leukopenia

Rare (0.01% to 0.1%): Neutropenia

Frequency not reported: Decreased lymphocytes, abnormal WBCs (unspecified), abnormal platelets, agranulocytosis, hematoma, leukocytosis, lymphadenopathy, decreased prothrombin, purpura, thrombocythemia, serious hematological side effects (e.g., pancytopenia, agranulocytosis, hemolytic anemia)

Postmarketing reports: Hemolytic anemia, pancytopenia, aplastic anemia, prothrombin time prolonged, INR prolonged

Nebulizer Solution:

-Uncommon (0.1% to 1%): Anemia, neutropenia, increased eosinophil count, decreased platelet count

Serious hematological side effects (e.g., pancytopenia, agranulocytosis, hemolytic anemia) have been reported after systemic administration of this drug.

Renal

Uncommon (0.1% to 1%): Abnormal renal function, acute renal failure (e.g., due to interstitial nephritis), increased blood creatinine

Frequency not reported: Renal calculi, allergic interstitial nephritis, increased nonprotein nitrogen

Postmarketing reports: Interstitial nephritis

Nebulizer Solution:

-Common (1% to 10%): Increased blood creatinine

-Uncommon (0.1% to 1%): Renal failure

A 73-year-old male developed vasculitis and acute renal failure within 3 days of starting oral therapy. Symptoms included significantly decreased urine output (0.5 to 0.7 L/day), palpable purpura, erythematous skin lesions, and increased serum creatinine (6.4 mg/dL) and BUN (190 mg/dL). The condition resolved within 4 weeks after discontinuation of this drug. Due to the possibility that this may have been an allergic reaction, rechallenge was not attempted.

Metabolic

Uncommon (0.1% to 1%): Anorexia, hyperglycemia, hyperkalemia, hypoglycemia

Frequency not reported: Decreased blood glucose, hypomagnesemia, thirst, aggravated diabetes mellitus, dehydration, hypokalemia, gout, hypernatremia, hypophosphatemia, weight decrease, fluid overload, hyponatremia, acidosis, symptomatic hypoglycemia, electrolyte abnormalities

Nebulizer Solution:

-Very common (10% or more): Anorexia

-Common (1% to 10%): Increased and decreased blood glucose

Fluoroquinolones:

-Frequency not reported: Attacks of porphyria

Hypoglycemia has been reported, especially in diabetic patients.

A 79-year-old male with type 2 diabetes mellitus developed severe hypoglycemia (blood glucose 6 mg/dL) and became unresponsive 6 hours after receiving 1 dose of this drug (250 mg IV). Blood glucose levels subsequently ranged between 40 to 159 mg/dL with dextrose doses and infusions; however, he did not regain consciousness and expired 2 days later.

Attacks of porphyria in patients with porphyria have been associated with fluoroquinolone use.

Genitourinary

Common (1% to 10%): Vaginitis

Uncommon (0.1% to 1%): Genital moniliasis

Frequency not reported: Dysmenorrhea, hematuria, dysuria, oliguria, urinary incontinence, urinary retention, leukorrhea, genital pruritus, ejaculation failure, impotence, albuminuria, candiduria, crystalluria, cylindruria, vaginal candidiasis, urinary tract infection

Nebulizer Solution:

-Common (1% to 10%): Vulvovaginal mycotic infection

Ocular

Rare (0.01% to 0.1%): Visual disturbances (e.g., blurred vision)

Frequency not reported: Ophthalmologic abnormalities (including cataracts, multiple punctate lenticular opacities), abnormal vision, eye pain, nystagmus, conjunctivitis, transient vision loss

Postmarketing reports: Vision disturbance (including diplopia), reduced visual acuity, blurred vision, scotomata, uveitis

Nebulizer Solution:

-Uncommon (0.1% to 1%): Visual disturbance

Oncologic

Frequency not reported: Carcinoma

Local

Common (1% to 10%): Injection site reactions (pain, reddening)

Frequency not reported: Injection site pain, injection site inflammation