MOXIFLOXACIN Drug Interactions: What You Need to Know

INTERACTIONS Interacting Drug Interaction Antacids, sucralfate, multivitamins, and other products containing multivalent cations Moxifloxacin absorption is decreased. Administer moxifloxacin hydrochloride tablet at least 4 hours before or 8 hours after these products. ( 2.2 , 7.1 , 12.3 , 17 )

Warfarin

Anticoagulant effect of warfarin may be enhanced. Monitor prothrombin time/INR, watch for bleeding. ( 6.4 , 7.2 , 12.3 ) Class IA and Class III antiarrhythmics: Proarrhythmic effect may be enhanced. Avoid concomitant use. ( 5.3 , 7.5 ) Antidiabetic agents Carefully monitor blood glucose ( 5.10 , 7.3 )

7.1 Antacids, Sucralfate, Multivitamins and Other Products Containing Multivalent Cations Quinolones form chelates with alkaline earth and transition metal cations. Oral administration of quinolones with antacids containing aluminum or magnesium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as VIDEX ® (didanosine) chewable/buffered tablets or the pediatric powder for oral solution, may substantially interfere with the absorption of quinolones, resulting in systemic concentrations considerably lower than desired. Therefore, moxifloxacin hydrochloride should be taken at least 4 hours before or 8 hours after these agents. [See Dosage and Administration (2.2) , Pharmacokinetics (12.3) , and Patient Counseling Information (17) .]

7.2 Warfarin Quinolones, including moxifloxacin hydrochloride, have been reported to enhance the anticoagulant effects of warfarin or its derivatives in the patient population. In addition, infectious disease and its accompanying inflammatory process, age, and general status of the patient are risk factors for increased anticoagulant activity. Therefore the prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if a quinolone is administered concomitantly with warfarin or its derivatives. [See Adverse Reactions (6.2 , 6.3) , Pharmacokinetics (12.3) , and Patient Counseling Information (17) .]

7.3 Antidiabetic Agents Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered. If a hypoglycemic reaction occurs, moxifloxacin hydrochloride should be discontinued and appropriate therapy should be initiated immediately. [See Warnings and Precautions (5.10) , Adverse Reactions (6.2) , and Patient Counseling Information (17) .]

7.4 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Although not observed with moxifloxacin hydrochloride in preclinical and clinical trials, the concomitant administration of a nonsteroidal anti-inflammatory drug with a quinolone may increase the risks of CNS stimulation and convulsions <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.6) , and Patient Counseling Information (17) ]</span> .

7.5 Drugs that Prolong QT There is limited information available on the potential for a pharmacodynamic interaction in humans between moxifloxacin hydrochloride and other drugs that prolong the QTc interval of the electrocardiogram. Sotalol, a Class III antiarrhythmic, has been shown to further increase the QTc interval when combined with high doses of intravenous (IV) moxifloxacin in dogs. Therefore, moxifloxacin hydrochloride should be avoided with Class IA and Class III antiarrhythmics. [See Warnings and Precautions (5.3) , Nonclinical Toxicology (13.2) , and Patient Counseling Information (17) .]

Moxifloxacin ophthalmic solution is contraindicated in patients with a history of hypersensitivity to moxifloxacin, to other quinolones, or to any of the components in this medication. . Moxifloxacin ophthalmic solution is contraindicated in patients with a history of hypersensitivity to moxifloxacin, to other quinolones, or to any of the components in this medication. ( 4 )

AND PRECAUTIONS Prolongation of the QT interval and isolated cases of torsades de pointes has been reported. Avoid use in patients with known prolongation, hypokalemia, and with drugs that prolong the QT interval. ( 5.6 , 7.4 , 8.5 ). Use caution in patients with proarrhythmic conditions such as clinically significant bradycardia or acute myocardial ischemia. ( 5.6 ) Serious and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, may occur after first or subsequent doses. Discontinue moxifloxacin at the first sign of skin rash, jaundice or any other sign of hypersensitivity. ( 5.7 , 5.8 ) Clostridioides difficile -associated diarrhea: Evaluate if diarrhea occurs. ( 5.10 ) High sodium load: each unit dose contains 52.5 mEq (1,207 mg) of sodium. Avoid in patients with sodium restriction. ( 5.11 )

5.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects Fluoroquinolones, including Moxifloxacin Injection, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting moxifloxacin. Patients of any age or without pre-existing risk factors have experienced these adverse reactions <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.2 , 5.3 , 5.4 )]</span> .

Discontinue Moxifloxacin

Injection immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including moxifloxacin, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.

5.2 Tendinitis and Tendon Rupture Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of tendinitis and tendon rupture in all ages <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )]</span> . This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur within hours or days of starting moxifloxacin or as long as several months after completion of therapy. Tendinitis and tendon rupture can occur bilaterally. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Discontinue moxifloxacin if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non- quinolone antimicrobial drug <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 ) and Patient Counseling Information ( 17 )]</span>. Avoid fluoroquinolones, including moxifloxacin, in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> .

5.3 Peripheral Neuropathy Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of peripheral neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones including moxifloxacin. Symptoms may occur soon after initiation of moxifloxacin and may be irreversible in some patients <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6 , 6.1 , 6.2 )]</span> . Discontinue moxifloxacin immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation. Avoid fluoroquinolones, including moxifloxacin, in patients who have previously experienced peripheral neuropathy <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 , 6.2 ) and Patient Counseling Information ( 17 )]</span>.

5.4 Central Nervous System Effects Psychiatric Adverse Reactions Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of psychiatric adverse reactions, including: toxic psychosis, hallucinations, or paranoia; depression or suicidal thoughts or acts; anxiety, agitation, or nervousness; confusion, delirium, disorientation, or disturbances in attention; insomnia or nightmares; and memory impairment. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin, discontinue moxifloxacin immediately and institute appropriate measures <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 , 6.2 )]</span>.

Central Nervous System Adverse Reactions

Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors. As with all fluoroquinolones, use moxifloxacin with caution in patients with known or suspected CNS disorders (for example, severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin, discontinue moxifloxacin immediately and institute appropriate measures [see Drug Interactions ( 7.3 ), Adverse Reactions ( 6.1 , 6.2 ) and Patient Counseling Information ( 17 )].

5.5 Exacerbation of Myasthenia Gravis Fluoroquinolones, including moxifloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Avoid moxifloxacin in patients with known history of myasthenia gravis <span class="opacity-50 text-xs">[see Patient Counseling Information ( 17 )]</span>.

5.6 QT Prolongation Moxifloxacin has been shown to prolong the QT interval of the electrocardiogram in some patients. Following oral dosing with 400 mg of moxifloxacin the mean (± SD) change in QTc from the pre-dose value at the time of maximum drug concentration was 6 msec (± 26) (n = 787). Following a course of daily intravenous dosing (400 mg; 1 hour infusion each day) the mean change in QTc from the Day 1 pre-dose value was 10 msec (± 22) on Day 1 (n = 667) and 7 msec (± 24) on Day 3 (n = 667). The drug should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia and patients receiving Class IA (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic agents, due to the lack of clinical experience with the drug in these patient populations. Pharmacokinetic studies between moxifloxacin and other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. An additive effect of moxifloxacin and these drugs cannot be excluded; therefore caution should be exercised when moxifloxacin is given concurrently with these drugs. In premarketing clinical trials, the rate of cardiovascular adverse events was similar in 798 moxifloxacin and 702 comparator treated patients who received concomitant therapy with drugs known to prolong the QTc interval. Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia, acute myocardial ischemia. The magnitude of QT prolongation may increase with increasing concentrations of the drug or increasing rates of infusion of the intravenous formulation. Therefore the recommended dose or infusion rate should not be exceeded. QT prolongation may lead to an increased risk for ventricular arrhythmias including torsades de pointes. No excess in cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin treatment in over 15,500 patients in controlled clinical studies, including 759 patients who were hypokalemic at the start of treatment, and there was no increase in mortality in over 18,000 moxifloxacin tablet treated patients in a postmarketing observational study in which ECGs were not performed. Elderly patients using Moxifloxacin Injection may be more susceptible to drug-associated QT prolongation <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.5 )]</span>. In addition, moxifloxacin should be used with caution in patients with mild, moderate, or severe liver cirrhosis <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 ) and Patient Counseling Information ( 17 )]</span>.

5.7 Hypersensitivity Reactions Serious anaphylactic reactions, some following the first dose, have been reported in patients receiving fluoroquinolone therapy, including moxifloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching.

Discontinue Moxifloxacin

Injection at the first appearance of a skin rash or any other sign of hypersensitivity [see Warnings and Precautions ( 5.7 ), Adverse Reactions ( 6 ) and Patient Counseling Information ( 17 )].

5.8 Other Serious and Sometimes Fatal Adverse Reactions Other serious and sometimes fatal adverse reactions, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including moxifloxacin. These events 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 Injection immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted <span class="opacity-50 text-xs">[see Patient Counseling Information ( 17 ) and Adverse Reactions ( 6.2 )]</span>.

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 Injection 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, 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 antibiotic 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 <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ) and Patient Counseling Information ( 17 )]</span>.

5.11 High Sodium Load Each unit dose of Moxifloxacin Injection contains 52.5 mEq (1,207 mg) of sodium. Avoid use of Moxifloxacin Injection in patients with congestive heart failure, elderly, and those with restricted sodium intake <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.5 ), Description ( 11 )]</span> .

5.12 Arthropathic Effects in Animals The oral administration of moxifloxacin caused lameness in immature dogs. 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 <span class="opacity-50 text-xs">[see Nonclinical Toxicology ( 13.2 )]</span>.

5.13 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 <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. If a hypoglycemic reaction occurs, discontinue moxifloxacin and initiate appropriate therapy immediately <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ), Drug Interactions ( 7.2 ) and Patient Counseling Information ( 17 )]</span> .

5.14 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 quinolone antibiotics after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 ) and Clinical Pharmacology ( 12.3 )]</span>.

5.15 Development of Drug Resistant Bacteria Prescribing moxifloxacin 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 <span class="opacity-50 text-xs">[see Patient Counseling Information ( 17 )]</span>.