Levaquin (Levofloxacin) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Serious and Otherwise Important Adverse Reactions

The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:

• Tendon Effects [see Warnings and Precautions (5.1)]
• Hypersensitivity Reactions [see Warnings and Precautions]
• Other Serious and Sometimes Fatal Reactions [see Warnings and Precautions]
• Hepatotoxicity [see Warnings and Precautions]
• Central Nervous System Effects [see Warnings and Precautions]
• Clostridium difficile -Associated Diarrhea [see Warnings and Precautions]
• Peripheral Neuropathy [see Warnings and Precautions]
• Prolongation of the QT Interval [see Warnings and Precautions]
• Musculoskeletal Disorders in Pediatric Patients [see Warnings and Precautions]
• Blood Glucose Disturbances [see Warnings and Precautions]
• Photosensitivity/Phototoxicity [see Warnings and Precautions]
• Development of Drug Resistant Bacteria [see Warnings and Precautions]

Hypotension has been associated with rapid or bolus intravenous infusion of LEVAQUIN^®. LEVAQUIN^® should be infused slowly over 60 to 90 minutes, depending on dosage [see Dosage and Administration].

Crystalluria and cylindruria have been reported with quinolones, including LEVAQUIN^®. Therefore, adequate hydration of patients receiving LEVAQUIN^® should be maintained to prevent the formation of a highly concentrated urine [see Dosage and Administration].

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to LEVAQUIN^® in 7537 patients in 29 pooled Phase 3 clinical trials. The population studied had a mean age of 50 years (approximately 74% of the population was < 65 years of age), 50% were male, 71% were Caucasian, 19% were Black. Patients were treated with LEVAQUIN^® for a wide variety of infectious diseases [see Indications and Usage (1) ] . Patients received LEVAQUIN^® doses of 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily. Treatment duration was usually 3–14 days, and the mean number of days on therapy was 10 days.

The overall incidence, type and distribution of adverse reactions was similar in patients receiving LEVAQUIN^® doses of 750 mg once daily, 250 mg once daily, and 500 mg once or twice daily. Discontinuation of LEVAQUIN^® due to adverse drug reactions occurred in 4.3% of patients overall, 3.8% of patients treated with the 250 mg and 500 mg doses and 5.4% of patients treated with the 750 mg dose. The most common adverse drug reactions leading to discontinuation with the 250 and 500 mg doses were gastrointestinal (1.4%), primarily nausea (0.6%); vomiting (0.4%); dizziness (0.3%); and headache (0.2%). The most common adverse drug reactions leading to discontinuation with the 750 mg dose were gastrointestinal (1.2%), primarily nausea (0.6%), vomiting (0.5%); dizziness (0.3%); and headache (0.3%).

Adverse reactions occurring in ≥1% of LEVAQUIN^®-treated patients and less common adverse reactions, occurring in 0.1 to <1% of LEVAQUIN^®-treated patients, are shown in Table 6 and Table 7, respectively. The most common adverse drug reactions (≥3%) are nausea, headache, diarrhea, insomnia, constipation, and dizziness.

Table 6: Common (≥1%) Adverse Reactions Reported in Clinical Trials with LEVAQUIN^®

System/Organ Class	Adverse Reaction	% (N=7537)
Infections and Infestations	moniliasis	1
Psychiatric Disorders	insomniaN = 7274 [see Warnings and Precautions]	4
Nervous System Disorders	headache dizziness [see Warnings and Precautions]	6 3
Respiratory, Thoracic and Mediastinal Disorders	dyspnea [see Warnings and Precautions]	1
Gastrointestinal Disorders	nausea diarrhea constipation abdominal pain vomiting dyspepsia	7 5 3 2 2 2
Skin and Subcutaneous Tissue Disorders	rash [see Warnings and Precautions] pruritus	2 1
Reproductive System and Breast Disorders	vaginitis	1N=3758 (women)
General Disorders and Administration Site Conditions	edema injection site reaction chest pain	1 1 1

Table 7: Less Common (0.1 to 1%) Adverse Reactions Reported in Clinical Trials with LEVAQUIN^® (N=7537)

System/Organ Class	Adverse Reaction
Infections and Infestations	genital moniliasis
Blood and Lymphatic System Disorders	anemia thrombocytopenia granulocytopenia [see Warnings and Precautions]
Immune System Disorders	allergic reaction [See Warnings and Precautions (5.2, 5.3) ]
Metabolism and Nutrition Disorders	hyperglycemia hypoglycemia [see Warnings and Precautions] hyperkalemia
Psychiatric Disorders	anxiety agitation confusion depression hallucination nightmare 1 [see Warnings and Precautions] sleep disorder anorexia abnormal dreaming
Nervous System Disorders	tremor convulsions [see Warnings and Precautions] paresthesia [see Warnings and Precautions] vertigo hypertonia hyperkinesias abnormal gait somnolence syncope
Respiratory, Thoracic and Mediastinal Disorders	epistaxis
Cardiac Disorders	cardiac arrest palpitation ventricular tachycardia ventricular arrhythmia
Vascular Disorders	phlebitis
Gastrointestinal Disorders	gastritis stomatitis pancreatitis esophagitis gastroenteritis glossitis pseudomembraneous/ C. difficile colitis [see Warnings and Precautions]
Hepatobiliary Disorders	abnormal hepatic function increased hepatic enzymes increased alkaline phosphatase
Skin and Subcutaneous Tissue Disorders	urticaria [see Warnings and Precautions]
Musculoskeletal and Connective Tissue Disorders	arthralgia tendonitis [see Warnings and Precautions] myalgia skeletal pain
Renal and Urinary Disorders	abnormal renal function acute renal failure [see Warnings and Precautions]

In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been noted in patients undergoing treatment with quinolones, including LEVAQUIN^®. The relationship of the drugs to these events is not presently established.

Postmarketing Experience

Table 8 lists adverse reactions that have been identified during post-approval use of LEVAQUIN^®. Because these reactions are reported voluntarily from a population of uncertain size, reliably estimating their frequency or establishing a causal relationship to drug exposure is not always possible.

Table 8: Postmarketing Reports Of Adverse Drug Reactions

System/Organ Class	Adverse Reaction
Blood and Lymphatic System Disorders	pancytopenia aplastic anemia leukopenia hemolytic anemia [see Warnings and Precautions] eosinophilia
Immune System Disorders	hypersensitivity reactions, sometimes fatal including:   anaphylactic/anaphylactoid reactions   anaphylactic shock   angioneurotic edema   serum sickness [see Warnings and Precautions (5.2, 5.3) ]
Psychiatric Disorders	psychosis paranoia isolated reports of suicide attempt and suicidal ideation [see Warnings and Precautions]
Nervous System Disorders	anosmia ageusia parosmia dysgeusia peripheral neuropathy [see Warnings and Precautions] isolated reports of encephalopathy abnormal electroencephalogram (EEG) dysphonia
Eye Disorders	vision disturbance, including diplopia visual acuity reduced vision blurred scotoma
Ear and Labyrinth Disorders	hypoacusis tinnitus
Cardiac Disorders	isolated reports of torsade de pointes electrocardiogram QT prolonged [see Warnings and Precautions ] tachycardia
Vascular Disorders	vasodilatation
Respiratory, Thoracic and Mediastinal Disorders	isolated reports of allergic pneumonitis [see Warnings and Precautions]
Hepatobiliary Disorders	hepatic failure (including fatal cases) hepatitis jaundice [see Warnings and Precautions 5.3, 5.4) ]
Skin and Subcutaneous Tissue Disorders	bullous eruptions to include:   Stevens-Johnson Syndrome   toxic epidermal necrolysis   erythema multiforme [see Warnings and Precautions] photosensitivity/photoxicity reaction [see Warnings and Precautions] leukocytoclastic vasculitis
Musculoskeletal and Connective Tissue Disorders	tendon rupture [see Warnings and Precautions] muscle injury, including rupture rhabdomyolysis
Renal and Urinary Disorders	interstitial nephritis [see Warnings and Precautions]
General Disorders and Administration Site Conditions	multi-organ failure pyrexia
Investigations	prothrombin time prolonged international normalized ratio prolonged muscle enzymes increased

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO LEVAQUIN

Possible Levaquin side effects / adverse reactions in 71 year old female

Reported by a physician from United States on 2007-10-11

Patient: 71 year old female weighing 70.8 kg (155.8 pounds)

Reactions: Fatigue, Visual Disturbance, Metabolic Encephalopathy, Hallucination, Somnolence, Eating Disorder, Lethargy

Adverse event resulted in: hospitalization

Suspect drug(s):
Aspirin
    Indication: Drug USE FOR Unknown Indication

Decadron
    Indication: Drug USE FOR Unknown Indication

Digoxin
    Indication: Drug USE FOR Unknown Indication

Duoneb
    Indication: Drug USE FOR Unknown Indication

Lasix
    Indication: Drug USE FOR Unknown Indication

Levaquin
    Indication: Drug USE FOR Unknown Indication

Mucomyst
    Indication: Drug USE FOR Unknown Indication

Radiation Therapy
    Dosage: 60gy cumulative dose
    Indication: Drug USE FOR Unknown Indication
    Start date: 2007-08-06
    End date: 2007-09-17

Temodar
    Dosage: 75mgm2 per day
    Administration route: Oral
    Indication: Glioblastoma Multiforme
    Start date: 2007-08-06
    End date: 2007-09-17

Other drugs received by patient: Colace; Lipitor; Lovenox; Metoprolol Tartrate

Possible Levaquin side effects / adverse reactions in 71 year old female

Reported by a individual with unspecified qualification from United States on 2007-10-12

Patient: 71 year old female weighing 69.9 kg (153.7 pounds)

Reactions: Oral Intake Reduced, Toxic Encephalopathy, Somnolence, Alpha Haemolytic Streptococcal Infection, Visual Disturbance, Blood Culture Positive, Hallucination, Metabolic Encephalopathy, Lethargy

Adverse event resulted in: hospitalization

Suspect drug(s):
Aspirin

Decadron
    Dosage: po
    Administration route: Oral

Digoxin

Duoneb

Lasix

Levaquin

Mucomyst

Other drugs received by patient: Colace; Lipitor; Lovenox; Temodar; Metoprolol

Possible Levaquin side effects / adverse reactions in 71 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2007-10-12

Patient: 71 year old female weighing 71.0 kg (156.2 pounds)

Reactions: Oral Intake Reduced, Fatigue, Alpha Haemolytic Streptococcal Infection, Visual Disturbance, Toxic Encephalopathy, Encephalopathy, Hallucination

Adverse event resulted in: hospitalization

Suspect drug(s):
Aspirin

Decadron

Digoxin

Duoneb

Lasix

Levaquin

Mucomyst

Radiation Therapy
    Dosage: total dose 60gy; total fractions given 22
    Start date: 2007-08-06
    End date: 2007-09-17

Temodar
    Administration route: Oral
    Indication: Glioblastoma Multiforme
    Start date: 2007-08-06
    End date: 2007-09-17

Other drugs received by patient: Colace; Lipitor; Lovenox; Metoprolol Tartrate