Moxifloxacin Hydrochloride (Page 4 of 14)

5.7 Other Serious and Sometimes Fatal Reactions

Other serious and sometimes fatal adverse reactions, some due to hypersensitivity, and some due to uncertain etiology, have been reported in patients receiving therapy with fluoroquinolones, including Moxifloxacin Tablets. These reactions may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

• Fever, rash, or severe dermatologic reactions (for example, toxic epidermal necrolysis, Stevens-Johnson syndrome)
• Vasculitis; arthralgia; myalgia; serum sickness
• Allergic pneumonitis
• Interstitial nephritis; acute renal insufficiency or failure
• Hepatitis; jaundice; acute hepatic necrosis or failure
• Anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities

Discontinue Moxifloxacin Tablets immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and institute supportive measures .

5.8 Hypersensitivity Reactions

Serious anaphylactic reactions, some following the first dose, have been reported in patients receiving fluoroquinolone therapy, including Moxifloxacin Tablets. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Discontinue Moxifloxacin Tablets at the first appearance of a skin rash or any other sign of hypersensitivity [see Warnings and Precautions (5.7)].

5.9 Risk of Aortic Aneurysm and Dissection

Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients. The cause for the increased risk has not been identified. In patients with a known aortic aneurysm or patients who are at greater risk for aortic aneurysms, reserve Moxifloxacin Tablets for use only when there are no alternative antibacterial treatments available.

5.10 Clostridioides difficile -Associated Diarrhea

Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Moxifloxacin Tablets, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated .

5.11 Arthropathic Effects in Animals

In immature dogs, oral administration of Moxifloxacin Tablets caused lameness. Histopathological examination of the weight- bearing joints of these dogs revealed permanent lesions of the cartilage. Related quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species [see Nonclinical Toxicology (13.2)].

5.12 Blood Glucose Disturbances

As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin. In moxifloxacin-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (for example, sulfonylurea) or with insulin. Severe cases of hypoglycemia resulting in coma or death have been reported. In diabetic patients, careful monitoring of blood glucose is recommended. If a hypoglycemic reaction occurs, discontinue Moxifloxacin Tablets and initiate appropriate therapy immediately [see Adverse Reactions ( 6.1), Drug Interactions ( 7.3) and Patient Counseling Information ( 17)] .

5.13 Photosensitivity/Phototoxicity

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (for example, burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of fluoroquinolones, including Moxifloxacin Tablets, after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Moxifloxacin Tablets should be discontinued if phototoxicity occurs [see Clinical Pharmacology (12.2)].

5.14 Development of Drug Resistant Bacteria

Prescribing Moxifloxacin Tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria .

6 ADVERSE REACTIONS

The following serious and otherwise important adverse reactions are discussed in greater detail in the warnings and precautions section of the label:

• Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects [see Warnings and Precautions (5.1)]
• Tendinitis and Tendon Rupture [see Warnings and Precautions (5.2)]
• Peripheral Neuropathy [see Warnings and Precautions (5.3)]
• Central Nervous System Effects [see Warnings and Precautions (5.4)]
• Exacerbation of Myasthenia Gravis [see Warnings and Precautions (5.5)]
• QT Prolongation [see Warnings and Precautions (5.6)]
• Other Serious and Sometimes Fatal Adverse Reactions [see Warnings and Precautions (5.7)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.8)]
• Risk of Aortic Aneurysm and Dissection [see Warnings and Precautions (5.9)]
• Clostridioides difficile -Associated Diarrhea [see Warnings and Precautions (5.10)]
• Blood Glucose Disturbances [see Warnings and Precautions (5.12)]
• Photosensitivity/Phototoxicity [see Warnings and Precautions (5.13)]
• Development of Drug Resistant Bacteria [see Warnings and Precautions (5.14)]