Moxifloxacin

Fifteen males and 5 females, mean age of 34 years, were given moxifloxacin under two conditions separated by a minimum 7-day washout period: alone as a single oral 400 mg dose, and immediately following 10 mg of IM morphine sulfate. Moxifloxacin serum concentrations were determined by a validated HPLC procedure. Pharmacokinetic parameters including Cmax, Tmax, AUC0-infinity, and t1/2 were estimated using noncompartmental methods and analyzed using ANOVA. Results: Moxifloxacin pharmacokinetics were similar between the two treatments. Geometric least square mean Cmax, values for moxifloxacin were 3.4 mg (alone) vs 2.8 mg/L (with morphine) (90% confidence interval (CI) of moxifloxacin alone vs with morphine sulfate was 71%-98%). Corresponding geometric mean AUC0-infinity values were 41.5 and 39.6 mgh/L (90% CI = 87%-104%). Tmax and t1/2 values for moxifloxacin were similar when coadministered with morphine. Conclusion: Moxifloxacin was well tolerated when taken with and without morphine sulfate. Administration of a single IM dose of morphine did not reduce the bioavailability or alter the elimination profile of oral moxifloxacin. Implications: Concurrent administration of morphine and moxifloxacin is unlikely to reduce the efficacy of this quinolone.

Pharmacokinetic interaction (decreased absorption of oral moxifloxacin). Moxifloxacin should be given at least 4 hours before or 8 hours after buffered didanosine (pediatric oral solution admixed with antacid).

Concomitant use of corticosteroids increases the risk of severe tendon disorders (e.g., tendinitis, tendon rupture), especially in geriatric patients older than 60 years of age.

Quinolones, including Avelox, 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.

For more Interactions (Complete) data for Moxifloxacin (17 total), please visit the HSDB record page.

Moxifloxacin, like other fluoroquinolones, is associated with a low rate (1% to 3%) of serum enzyme elevations during therapy. These abnormalities are generally mild, asymptomatic and transient, resolving even with continuation of therapy. Moxifloxacin has been linked to rare but occasionally severe and even fatal cases of acute liver injury. The time to onset is typically short (1 day to 3 weeks) and the presentation is often abrupt with nausea, fatigue, abdominal pain and jaundice. The pattern of serum enzyme elevations can be either hepatocellular or cholestatic, cases with the shorter times to onset usually being more hepatocellular. In addition, the onset of illness may occur a few days after the medication is stopped. Many (but not all) cases have prominent allergic manifestations with fever and rash, and the liver injury may occur in the context of a generalized hypersensitivity reaction (Case 1). Autoantibodies are usually not present. Cases with a cholestatic pattern of enzymes may run a prolonged course but are usually self-limiting, although at least one case of chronic cholestasis and vanishing bile duct syndrome leading to liver failure has been published. Most reported cases have been mild with recovery within 4 to 8 weeks of onset.

Moxifloxacin is associated with various adverse effects and can result in severe injuries in some cases. The common adverse drug reactions include gastrointestinal symptoms such as nausea, abdominal pain, vomiting, and diarrhea. Patients may experience headaches, dizziness, and, in rare cases, more severe central nervous system (CNS) effects such as confusion or hallucinations. A significant and potentially severe adverse effect of moxifloxacin is the increased risk of tendonitis and tendon rupture, especially in older adults and those concurrently using corticosteroids. Reports indicate that moxifloxacin can lead to changes in heart rhythm (QTc interval prolongation) and an elevated risk of arrhythmias, especially in patients with preexisting heart conditions. Some patients may experience skin rashes, itching, lips, face, and throat swelling due to an allergic reaction to moxifloxacin. Severe allergic reactions such as anaphylaxis are rare but possible. Moxifloxacin has been associated with increased photosensitivity, potentially resulting in heightened susceptibility to sunburn. According to the reports, there are indications of musculoskeletal pain and joint discomfort.

Moxifloxacin is excreted in the breast milk of rats. Moxifloxacin may also be excreted in human milk. Because of the potential for serious adverse reactions in infants who are nursing from mothers taking Avelox, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Currently, no specific antidote is available for moxifloxacin overdose. Therefore, treatment focuses primarily on symptom management and essential supportive care, including airway maintenance, oxygen supplementation, and hemodynamic support. Gastric lavage or activated charcoal may be considered to limit further drug absorption, depending on the patient's level of consciousness. If the patient is alert and capable of protecting their airway, gastric lavage or activated charcoal can be used to prevent systemic absorption.

The major factor in removal of fluoroquinolone antiobiotics such as moxifloxacin, is sorption to sludge. This along with long-term cycling and persistence of these drugs in the sewage treatment plant has made activated sludge a large reservoir of fluoroquinolone antibiotics(1).

/HUMAN EXPOSURE STUDIES/ ... Nine men and 9 women participated in a double-blind, randomized, placebo-controlled, crossover study. Each participant received single oral doses (400 mg and 800 mg) of moxifloxacin or placebo. At the time of expected moxifloxacin maximum concentration, several electrocardiographic recordings were obtained at rest and during the course of a submaximal exercise test. QT interval and the corresponding RR interval value were measured within a wide range of RR intervals in each subject. ANOVA showed that both moxifloxacin doses increased mean QT intervals compared with placebo. The mean QT interval duration at RR = 1000 ms was 379 +/- 24 ms during placebo, 394 +/- 33 ms during moxifloxacin 400 mg (P < .05), and 396 +/- 28 ms during moxifloxacin 800 mg (P < .05). Moxifloxacin-induced QT interval prolongation remained significant at all tested heart rates. The increase in QT interval duration relative to placebo remained between 2.3% +/- 2.8% and 4.5% + 3.8% across the range of RR intervals tested. Moxifloxacin prolongs QT interval duration. The amplitude of this effect is small, and the risk of moxifloxacin-induced torsades de pointes is expected to be minimal when the drug is administered at the recommended dose of 400 mg/d. However, moxifloxacin should not be used in patients with predisposing factors of torsades de pointes such as electrolyte disturbances and bradycardia or during coadministration of proarrhythmic drugs.

/CASE REPORTS/ Torsade de pointes (TdP) is increasingly recognized as a complication of drug therapy. The most common cause of drug-induced QT prolongation is inhibition of the rapidly activating component of the delayed potassium current (I(Kr)). Moxifloxacin, a widely used fluoroquinolone, is a weak I(Kr) inhibitor and has been associated with QT prolongation. ... /The authors/ report a case of marked QT prolongation (618 ms) and TdP associated with moxifloxacin use. Although it is difficult to predict which patients are at risk from TdP, careful assessment of the risk/benefit ratio is important before prescribing drugs known to cause QT prolongation.

/CASE REPORTS/ An 87-year-old woman was admitted to the hospital for pneumonia, and antibiotic therapy with intravenous moxifloxacin 400 mg/day was initiated. The patient was noted to have significant QTc interval prolongation 2 hours after administration of moxifloxacin and developed torsade de pointes 8-10 hours after moxifloxacin administration. She was converted back to normal sinus rhythm after a precordial thump. Moxifloxacin was discontinued, and the woman's QTc interval subsequently returned to baseline.Torsade de pointes is a life-threatening arrhythmia that has previously been associated with the use of fluoroquinolones. ... According to the Naranjo probability scale, the episode in this case was probably related to administration of intravenous moxifloxacin.

/CASE REPORTS/ Torsade de pointes occuring due to a long QT interval is a rare but potentially fatal arrhythmia. Acquired long QT develops most commonly because of drugs that prolong ventricular repolarization. It has been reported that fluoroquinolone antimicrobials prolong the corrected QT interval but rarely cause torsade de pointes. A patient with torsade de pointes risk factors (female sex, advanced age, extreme bradycardia and renal failure) who developed the condition on the fourth day of 400 mg/day of oral moxifloxacin treatment is presented. After the moxifloxacin was stopped, the corrected QT interval normalized and a permanent cardiac pacemaker was implanted. During 11 months of follow-up, arrhythmia did not recur.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

moxifloxacin

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Acute Exposure/ The purpose of this study was to investigate the effects of moxifloxacin on the QT interval in conscious, healthy dogs. Four male mongrel dogs were chronically instrumented for the measurement of arterial blood pressure, left ventricular blood pressure, cardiac output, electrocardiograms (ECGs), and body temperature. Animals were administered a 1-hr iv infusion of moxifloxacin once per day via a catheter in the cephalic vein. Each dog received all doses (0, 1, 10, 25 and 50 mg/kg) in an escalating fashion. Moxifloxacin caused a statistically significant increase in arterial blood pressure at 50 mg/kg. A dose-response effect on QT and QTc prolongation was observed. A statistically significant prolongation in the QT interval was observed at 10, 25 and 50 mg/kg and a prolongation of QTc was observed at 25 and 50 mg/kg. These effects occurred at clinically relevant plasma concentrations.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Quinolones have been shown to cause arthropathy in immature animals. In studies in juvenile dogs oral doses of moxifloxacin = 30 mg/kg/day (approximately 1.5 times the maximum recommended human dose based upon systemic exposure) for 28 days resulted in arthropathy.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In an oral pre- and postnatal development study conducted in rats, effects observed at 500 mg/kg/day included slight increases in duration of pregnancy and prenatal loss, reduced pup birth weight and decreased neonatal survival. Treatment-related maternal mortality occurred during gestation at 500 mg/kg/day in this study.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ There was no evidence of teratogenicity when pregnant cynomolgus monkeys were given oral doses as high as 100 mg/kg/day (2.5 times the maximum recommended human dose based upon systemic exposure). An increased incidence of smaller fetuses was observed at 100 mg/kg/day.

For more Non-Human Toxicity Excerpts (Complete) data for Moxifloxacin (7 total), please visit the HSDB record page.

No dosage adjustment is recommended for mild, moderate, or severe hepatic insufficiency (Child-Pugh Classes A, B, or C). However, due to metabolic disturbances associated with hepatic insufficiency, which may lead to QT prolongation, Avelox should be used with caution in these patients.

Use of moxifloxacin should be avoided in patients with known prolongation of the QT interval, in those with uncorrected hypokalemia, ... .

Avoid Avelox in patients with known history of myasthenia gravis.

Concomitant use of corticosteroids increases the risk of severe tendon disorders (e.g., tendinitis, tendon rupture), especially in geriatric patients older than 60 years of age.

For more Populations at Special Risk (Complete) data for Moxifloxacin (7 total), please visit the HSDB record page.

While data specific to moxifloxacin were not located(SRC, 2012), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through soils(1).

In the event of acute overdose ... adequate hydration /should be/ maintained. ECG monitoring is recommended due to the possibility of QT interval prolongation. The patient should be carefully observed and given supportive treatment. The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase of systemic moxifloxacin exposure. About 3% and 9% of the dose of moxifloxacin, as well as about 2% and 4.5% of its glucuronide metabolite are removed by continuous ambulatory peritoneal dialysis and hemodialysis, respectively.

Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. replace fluid losses resulting from gastroenteritis with IV crystalloids. ... /Antibacterial agents/

Decontamination: Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antibacterial agents/

Enhanced elimination: Most antibiotics are excreted unchanged in the urine, so maintenance of adequate urine flow is important. The role of forced diuresis is unclear. Hemodialysis is not usually indicated, except perhaps in patients with renal dysfunction and a high level of a toxic agent. ... /Antibacterial agents/

For more Antidote and Emergency Treatment (Complete) data for Moxifloxacin (7 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including moxifloxacin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Moxifloxacin hydrochloride/

MEDICATION

Use (kg; approx.) in Germany (2009): >2500

Table: Moxifloxacin Hydrochloride Preparations [Table#7970]

Ophthalmic: Solution: 0.5% (of moxifloxacin) Vigamox (Alcon). /Moxifloxacin hydrochloride/

Moxeza

Vigamox