What is the safety profile of Moxifloxacin (a fluoroquinolone antibiotic)?

Moxifloxacin Safety Profile

Moxifloxacin should be used with caution due to its serious adverse reactions including tendinitis, tendon rupture, peripheral neuropathy, central nervous system effects, and exacerbation of myasthenia gravis, and should be reserved for patients who have no alternative treatment options for certain indications. 1

Major Safety Concerns

Serious Adverse Reactions

Moxifloxacin, like other fluoroquinolones, carries an FDA boxed warning for several potentially disabling and irreversible serious adverse reactions:

• Tendinitis and tendon rupture: Risk is increased in patients over 60 years, those taking corticosteroids, and patients with kidney, heart, or lung transplants 1
• Peripheral neuropathy: Can result in sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons 1
• Central nervous system effects: Including convulsions, increased intracranial pressure, toxic psychosis, nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts 1
• Exacerbation of myasthenia gravis: Can cause severe reactions including deaths and requirement for ventilatory support 1

Cardiovascular Effects

• QT interval prolongation: Moxifloxacin prolongs the QT interval by a mean of 6 msec (±26) 2
• Should be avoided in patients with:
  • Known QT prolongation
  • Ventricular arrhythmias including torsade de pointes
  • Proarrhythmic conditions (bradycardia, acute myocardial ischemia)
  • Uncorrected hypokalemia or hypomagnesemia
  • Patients taking Class IA or III antiarrhythmics 1

Hypersensitivity Reactions

• Serious and sometimes fatal hypersensitivity reactions can occur, including:
  • Skin rash, severe dermatologic reactions (toxic epidermal necrolysis, Stevens-Johnson syndrome)
  • Vasculitis, arthralgia, myalgia, serum sickness
  • Allergic pneumonitis
  • Interstitial nephritis, acute renal failure
  • Hepatitis, jaundice, acute hepatic necrosis 1

Gastrointestinal Effects

Gastrointestinal complaints are the most common adverse drug reactions:

• Nausea: 7.1% (oral) and 3.1% (IV) 3
• Diarrhea: 5.2% (oral) and 6.2% (IV) 3
• Risk of Clostridium difficile-associated diarrhea 1

Special Populations

Elderly Patients

• Increased risk for severe tendon disorders, especially with concomitant corticosteroid therapy
• More susceptible to drug-associated effects on the QT interval
• No dosage adjustment needed based on age alone 1

Renal Impairment

• No dosage adjustment necessary in patients with renal impairment, including those requiring hemodialysis or continuous ambulatory peritoneal dialysis 1

Hepatic Impairment

• No dosage adjustment recommended for mild, moderate, or severe hepatic insufficiency
• Should be used with caution due to metabolic disturbances that may lead to QT prolongation 1

Pregnancy and Lactation

• Should be avoided in pregnancy due to teratogenic effects 4
• It is not known if moxifloxacin is present in human milk, but animal studies suggest it may be excreted in human milk 1

Pediatric Use

• Not approved for use in patients under 18 years of age
• Causes arthropathy in juvenile animals 1

Drug Interactions

• Antacids, sucralfate, multivitamins containing metal cations: Decrease moxifloxacin absorption; take moxifloxacin at least 4 hours before or 8 hours after these products 1
• Warfarin: Enhanced anticoagulant effect; monitor prothrombin time/INR and bleeding 1
• Class IA and Class III antiarrhythmics: Proarrhythmic effect may be enhanced; avoid concomitant use 1
• Antidiabetic agents: Carefully monitor blood glucose 1

Long-term Safety Data

A comprehensive analysis of 14 years of clinical data (1996-2010) showed:

• Overall incidence rates of adverse events were globally similar between moxifloxacin and comparator groups
• Incidence rates of hepatic disorders, tendon disorders, clinical surrogates of QT prolongation, serious cutaneous reactions, and C. difficile-associated diarrhea were similar with moxifloxacin and comparators 5

Clinical Considerations

• Moxifloxacin is generally well tolerated when used according to label recommendations
• Discontinuation rates due to adverse drug reactions: 2.7% (oral) and 6.0% (IV) 3
• Mortality rates: 0.3% (oral) and 4.0% (IV), similar to comparator groups 3
• Lack of significant drug interactions makes it an option in diabetic patients, the elderly, and those with renal impairment when benefits outweigh risks 3

Appropriate Use

Moxifloxacin should be reserved for patients who have no alternative treatment options for certain indications such as acute bacterial sinusitis and acute bacterial exacerbation of chronic bronchitis 1. For other approved indications (community-acquired pneumonia, skin infections, complicated intra-abdominal infections, plague), it should be used when the benefits outweigh the risks of adverse reactions.