Moxifloxacin hydrochloride tablets instruction

Date of approval.
Date of revision.
Moxifloxacin Hydrochloride Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician.
Use in food, feed processing and breeding is strictly prohibited.
Warning: Serious adverse reactions, including tendonitis and tendon rupture, peripheral neuropathy, central nervous system effects and increased myasthenia gravis
Concurrent disabling and potentially irreversible serious adverse reactions have been reported with fluoroquinolones (including moxifloxacin hydrochloride) (see [Precautions]), including
tendonitis and tendon rupture (see [Precautions])
Peripheral neuropathy (see [Precautions])
Central nervous system effects (see [Precautions]).
When these serious adverse reactions occur (see [Precautions]), moxifloxacin hydrochloride should be discontinued immediately and fluoroquinolones (including moxifloxacin hydrochloride) should be avoided
Fluoroquinolones (including moxifloxacin hydrochloride) may exacerbate the symptoms of muscle weakness in patients with myasthenia gravis. Moxifloxacin hydrochloride should be avoided in patients with a known history of myasthenia gravis (see [Precautions])
Because serious adverse reactions have been reported with fluoroquinolones (including moxifloxacin hydrochloride) (see [Precautions]), moxifloxacin hydrochloride should be used only in the absence of other drug therapy in patients with the following indications.
Acute bacterial sinusitis (see [Indications] and [Dosage])
Acute exacerbation of chronic bronchitis (see [Indications] and [Dosage]) [Drug Name
Generic name: Moxifloxacin Hydrochloride Tablets
English name: Moxifloxacin Hydrochloride Tablets
Hanyu Pinyin: Yansuan Moxishaxing Pian
Ingredients
Main ingredients: Moxifloxacin Hydrochloride
Chemical name: 1-cyclopropyl-7-{S,S-2,8-diazo-dicyclo[4.3.0]non-8-yl}-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride.
Chemical structure formula.
Molecular formula: C21H24FN3O4-HCl
Molecular weight: 437.9
Properties
This product is white or off-white oval film-coated tablets, yellow or light yellow after removing the coating.
Indications
In order to reduce the occurrence of drug-resistant bacteria and to maintain the effectiveness of moxifloxacin hydrochloride and other antibacterial drugs, moxifloxacin hydrochloride should be used only for the treatment of infections that have been proven or strongly suspected to be caused by susceptible bacteria.
In cases where culture and drug sensitivity information is obtained, the choice to continue or switch to another drug should be based on the results. In the absence of these data, the epidemiology and susceptibility profile of the local causative organism may be helpful in the empirical selection of therapeutic agents.
Appropriate culture and drug sensitivity testing should be performed prior to treatment to isolate and identify the microorganism causing the infection and to determine its susceptibility to moxifloxacin hydrochloride.
Moxifloxacin hydrochloride may have been selected for treatment prior to obtaining culture results, and appropriate treatment should be selected once culture results are obtained.
Moxifloxacin hydrochloride tablets are used for the treatment of the following infections caused by sensitive bacteria in adults (≥18 years of age).
1. Acute bacterial sinusitis: caused by Streptococcus pneumoniae, Haemophilus influenzae or Catamorium.
Because serious adverse reactions have been reported with fluoroquinolones (including moxifloxacin hydrochloride), and because acute bacterial sinusitis is self-limiting in some patients, moxifloxacin hydrochloride should be used only when no other medication is available.
2. Acute exacerbations of chronic bronchitis: caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus, or Catamorax.
Because serious adverse reactions have been reported with fluoroquinolones (including moxifloxacin hydrochloride), and because for some patients, acute attacks of chronic bronchitis are self-limiting, moxifloxacin hydrochloride should be used only when no other medications are available.
3. Community-acquired pneumonia: caused by Streptococcus pneumoniae (including multidrug-resistant strains), Haemophilus influenzae, Cattamora, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydia pneumoniae.
4, Uncomplicated skin and skin tissue infections: caused by methicillin-sensitive Staphylococcus aureus or Streptococcus pyogenes.
5, complicated skin and skin tissue infection: caused by methicillin-sensitive Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae.
6, complex intra-abdominal infections: caused by Escherichia coli, Bacteroides fragilis, Streptococcus pharyngeus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides polymorphicus or Streptococcus pepticus spp. including abdominal abscesses.
7. Plague, including pneumonic plague and septicemic plague caused by Yersinia pestis (Y. pestis) in adults, can also prevent plague.
For feasibility reasons, clinical studies of effectiveness in humans are not possible; therefore, this indication is determined based on animal effectiveness study data only.
Specification】0.4g (by moxifloxacin).
Dosage]
Moxifloxacin hydrochloride tablets are used for the treatment of infectious diseases (see [Indications]). The generic dosage is shown below, but must be finalized by the clinician in conjunction with the severity of the disease.
1. Adult dose, duration of treatment and method of administration
The dose of moxifloxacin hydrochloride tablets is 0.4g (orally) every 24 hours. The duration of treatment depends on the type of infection, as described in Table 1.
Table 1: Type of infection, dose and duration of treatment
Type of infection Dose duration per 24 hours (days) Acute bacterial sinusitis 0.4g10 Acute exacerbation of chronic bronchitis 0.4g5 Community-acquired pneumonia 0.4g7-14 Uncomplicated skin and skin tissue infection 0.4g7Complicated skin and skin tissue infection 0.4g7-21Complicated intra-abdominal infection 0.4g5-14 Plaguea 0.4g10-14a ) The medication should be started immediately after suspected or confirmed exposure to Yersinia pestis.
2. Elderly patients
Dose adjustment is not necessary for elderly patients.
3.Patients with renal or hepatic insufficiency
Hepatic impairment.
There is no clinically significant difference in plasma drug concentrations between patients with mild to moderate hepatic impairment (Child Pugh class A or B) and healthy volunteers or patients with normal hepatic function.
Renal impairment.
No dose adjustment is required in patients with impaired renal function (including creatinine clearance ≤ 30 ml/min/1.73 m2 ) and in patients on chronic dialysis, such as hemodialysis and continuous ambulatory peritoneal dialysis.
4. Dosing instructions
Oral formulation can be taken with or without food, drinking water is not limited.
Interaction with multivalent cationic drugs
Moxifloxacin hydrochloride tablets should be taken at least 4 hours prior to or 8 hours after the use of chewable/slow-release tablets or pediatric oral granules containing magnesium, aluminum, iron or zinc, including antacids, aluminum thioglycollate, multivitamins and dehydroxylated inosine.
When moxifloxacin hydrochloride is prescribed to treat a bacterial infection, the patient should be informed that the drug should be used as prescribed, although the condition usually improves early in the course of treatment. Skipping doses or not completing the entire course of treatment may (1) decrease the effectiveness of emergency treatment; and (2) increase the likelihood that bacterial resistance will develop and future treatment with moxifloxacin hydrochloride or other antibacterial agents will not be possible.
5. Ethnic differences
Possible inter-racial differences were tested in Caucasian, Japanese, black and other racial populations and no clinically relevant pharmacokinetic differences were found. Therefore, there is no need to adjust the drug dose among different races.
[Adverse reactions].
1. Serious and other important adverse reactions
Disabling and potentially irreversible serious adverse reactions, including tendinitis and tendon rupture, peripheral neuropathy and central nervous system effects
Tendinopathy and tendon rupture
Prolonged QT interval
Allergic reactions
Other serious and sometimes fatal reactions
Central nervous system effects
Clostridium difficile-associated diarrhea
Peripheral neuropathy
Interference with blood glucose
Photosensitivity/phototoxicity
Formation of drug-resistant bacteria
The above adverse reactions are described in detail under [Precautions].
Cardiovascular system: QT interval prolongation, tip-twisting ventricular tachycardia, ventricular arrhythmias
Central nervous system: Convulsions, toxic psychosis, tremor, agitation, anxiety, dizziness, confusion, hallucinations, delusions, depression, nightmares, insomnia, seizures, and in rare cases, suicidal thoughts or actions
Peripheral neuropathy: sensory confusion, sensory dullness, pain to touch, pain, burning, tingling, numbness, weakness, or abnormalities in light touch, pain, temperature, position, and vibration, polyneuritis
Skeletal muscle system: arthralgia, myalgia, muscle weakness, hypertonic tendonitis, tendon rupture, worsening of myasthenia gravis
Hypersensitivity reactions: urticaria, pruritus and other severe skin reactions (e.g., toxic epidermolysis bullosa, erythema multiforme), dyspnea, angioneurotic edema (including edema/swelling of the tongue, throat, pharynx, or face), cardiovascular collapse, hypotension, loss of consciousness, airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), allergic pneumonia, anaphylaxis
Hepatobiliary system: hepatitis, jaundice, acute hepatic necrosis or liver failure
Urologic system: acute renal insufficiency or renal failure
Hematologic system: anemia, including hemolytic anemia and aplastic anemia, thrombocytopenia, including thrombotic thrombocytopenic purpura, leukopenia, granulocytopenia, holocytopenia, and/or other hematologic disorders
Other: fever, vasculitis, serum sickness, Clostridium difficile-associated diarrhea, dysglycemia, photosensitivity/photototoxicity
2. Experience with clinical trials
The incidence of adverse drug reactions observed in clinical trials cannot be directly compared with another drug and may not reflect the actual incidence due to the different conditions under which the clinical trials were conducted.
The following data describe 71 phase II-IV clinical trials of moxifloxacin hydrochloride with active drug control under different conditions. A total of 14,981 patients were administered moxifloxacin hydrochloride, with a mean age of 50 years (approximately 73% of patients were younger than 65 years), 50% were male, 63% were white, 12% were Asian, and 9% were black. Patients received 0.4 g moxifloxacin hydrochloride once daily by mouth, intravenous drip, or sequential dosing (intravenous drip followed by oral dosing). Treatment duration was usually 6-10 days, with a mean of 9 days of treatment.
Moxifloxacin hydrochloride was discontinued in 5% of patients due to adverse events. 4.1% of patients received 0.4 g of moxifloxacin hydrochloride orally, 3.9% of patients received 0.4 g intravenously, and 8.2% of patients were treated with sequential therapy 0.4 g orally/intravenously. The most common adverse events (>0.3%) leading to discontinuation in patients receiving the oral 0.4g dose were nausea, diarrhea, dizziness, and vomiting. In patients on the intravenous 0.4 g dose, the most common adverse event leading to discontinuation was skin rash. In patients receiving sequential injectable/oral treatment doses, the most common adverse events leading to discontinuation were diarrhea and fever.
Among patients treated with moxifloxacin hydrochloride, adverse reactions ≥1% and less common adverse reactions (incidence of 0.1% to <1%) are shown in Tables 2 and 3, respectively. The most common adverse drug reactions (3%) were nausea, diarrhea, headache, and dizziness.
Table 2: Common (≥1%) adverse reactions in clinical trials of moxifloxacin hydrochloride with active control drugs
System Organ Classification Adverse Reaction Incidence % (N=14981) Blood and lymphatic system disorders Anemia1 Gastrointestinal disorders Nausea
Diarrhea
Vomiting
Constipation
Abdominal pain
Indigestion7
6
2
2
2
1 Systemic diseases and administration site reactions Fever1 Elevated glutamate transaminase on various tests1 Metabolic and nutritional disorders Hypokalemia1 Neurological disorders Headache
Dizziness4
3 Psychiatric disorders insomnia2 Table 3: Moxifloxacin hydrochloride uncommon in clinical trials with active control drugs (0.1% – <1%)
Adverse reactions (N=14981)
System organ classification adverse reactions Blood and lymphatic system disorders Thrombocytosis, eosinophilia, neutropenia, thrombocytopenia, leukopenia, leukocytosis Heart disorders Atrial fibrillation, palpitations, tachycardia, angina, heart failure, cardiac arrest, bradycardia Ear and vagus disorders Vertigo, tinnitus Eye organ disorders Blurred vision Gastrointestinal disorders Oral dryness abdominal discomfort, intestinal gas, bloating, gastritis, gastroesophageal reflux disease systemic diseases and administration site reactions fatigue, chest pain, weakness, pain, discomfort, extravasation of fluids, edema, chills, chest discomfort, facial pain hepatobiliary system diseases abnormal liver function infectious and invasive diseases candidiasis, vaginal infections, fungal infections, gastroenteritis various tests elevated glutamate transaminase, elevated glutamine transpeptidase Alkaline phosphatase, prolonged electrocardiogram QT interval, elevated blood lactate dehydrogenase, elevated blood amylase, elevated lipase, elevated blood creatinine, elevated blood urea, decreased erythrocyte pressure product, prolonged prothrombin time, elevated eosinophil count, prolonged partial prothrombin activation time, elevated blood triglycerides, elevated blood uric acid Metabolic and nutritional disorders Hyperglycemia, anorexia, hypoglycemia, Musculoskeletal and connective tissue disorders Back pain, extremity pain, arthralgia, muscle spasm, skeletal pain Neurological disorders Taste disturbance, sleepiness, tremor, drowsiness, sensory abnormalities, tension headache, sensory dullness, syncope Mental disorders Anxiety, confusion, agitation, depression, nervousness, irritability, hallucinations, disorientation Kidney and urinary disorders Kidney failure, urination Difficulties reproductive system and breast diseases vulvar itching respiratory system, chest and mediastinal diseases dyspnea, asthma, shortness of breath, bronchospasm skin and subcutaneous tissue diseases rash, pruritus, hyperhidrosis, erythema, urticaria, atopic dermatitis, night sweats vascular diseases hypertension, hypotension, phlebitis 3. Changes in laboratory test parameters
Changes in the following laboratory test parameters, which are not listed in the table above, were derived from the occurrence and higher incidence in ≥ 2% of patients than in controls, but without considering the causal relationship with drugs.
Elevated erythrocyte mean hemoglobin, neutrophils, white blood cell count, prothrombin time ratio, calcium ion, chloride ion, clear protein, globulin, and bilirubin; decreased hemoglobin, erythrocytes, neutrophils, eosinophils, basophils, prothrombin time ratio, glucose, partial pressure of oxygen, bilirubin, and amylase.
It cannot be determined that the above laboratory abnormalities are due to the drug or the primary disease being treated.
4. Post-marketing experience
Table 4 lists the post-marketing adverse reactions that have been reported after definitive use of moxifloxacin hydrochloride. Since these reactions were spontaneously reported from an undetermined number of people, it is not possible to fully estimate the incidence or determine a causal relationship with the use of the drug on this basis.
Table 4: Post-marketing reported adverse drug reactions
System/Organ Classification Adverse Reactions Blood and Lymphatic System Disorders Granulocyte Deficiency, Pancytopenia Cardiac Disorders Ventricular tachyarrhythmias (including, in very rare cases, cardiac arrest and tip-twisting ventricular tachycardia), usually occurring when patients are complicated by severe drug-related arrhythmias Ear and Labyrinth Disorders Hearing impairment, including deafness (generally reversible) Eye Organ Disorders Visual Loss (especially during central nervous system reactions, mostly transient) Hepatobiliary system disorders hepatitis (mainly bilious), liver failure (including fatal cases), jaundice, acute hepatic necrosis Immune system disorders allergic reactions, anaphylaxis, angioedema (including laryngeal edema) Musculoskeletal and connective tissue disorders tendon rupture Neurological disorders coordination disorders, gait abnormalities, myasthenia gravis (exacerbation), muscle weakness, peripheral neuropathy (possibly irreversible), polyneuropathy psychiatric disorders psychotic reactions (very rare cases may culminate in self-harm behaviors such as suicidal ideation/thoughts or attempts) renal and urinary disorders renal dysfunction, interstitial nephritis respiratory, thoracic and mediastinal disorders allergic pneumonia skin and subcutaneous tissue disorders photosensitivity/phototoxic reactions, Stevens-Johnson syndrome, toxic epidermolysis bullosa [Contraindicated
1, known hypersensitivity to moxifloxacin, other quinolones or any excipients is prohibited.
2, Pregnant and lactating women are contraindicated.
3, Due to limited clinical data, moxifloxacin hydrochloride should be contraindicated in patients with hepatic impairment (Child Pugh Class C) and in patients with elevated transaminases greater than 5 times the upper limit of normal values.
4. Contraindicated in patients under 18 years of age.
5. Contraindicated in patients with a history of tendon disease/conditions associated with quinolone therapy.
6. Data from preclinical studies and studies in humans have shown that cardiac electrophysiological changes have been observed following exposure to moxifloxacin, as evidenced by a prolonged QT interval.
Due to safety considerations, moxifloxacin is contraindicated in patients who are.
(1) Patients with congenital or proven acquired QT interval prolongation.
(2) Patients with electrolyte disturbances, particularly uncorrected hypokalemia.
(3) Patients with clinically significant bradycardia.
(4) Patients with clinically significant heart failure with reduced left ventricular ejection fraction.
(5) Patients with previous symptomatic arrhythmias.
7. Moxifloxacin hydrochloride should not be used simultaneously with other drugs that can prolong the QT interval.
Precautions
1. Disabling and potentially irreversible serious adverse reactions, including tendonitis and tendon rupture, peripheral neuropathy, central nervous system effects
Disabling and potentially irreversible serious adverse reactions have been reported with fluoroquinolones (including moxifloxacin hydrochloride) in different organ systems of the body in the same patient, usually including: tendonitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy and central nervous system reactions (hallucinations, anxiety, depression, insomnia, severe headache and confusion). These adverse reactions can occur from hours to weeks after the use of moxifloxacin hydrochloride. The occurrence of these adverse reactions has been reported in patients of any age with no prior associated risk factors.
2. Tendinopathy and tendon rupture
Fluoroquinolones, including moxifloxacin hydrochloride, put patients of all ages at increased risk for tendinopathy and tendon rupture. This adverse effect most often occurs in the Achilles tendon, which may require surgical repair for rupture. Tendonitis and tendon rupture have also been reported in the shoulder, hand, biceps, thumb, and other tendon sites. Tendonitis and tendon rupture can occur hours or days after starting moxifloxacin, or months after finishing treatment. Tendonitis and tendon rupture can occur bilaterally. This risk is further increased in older patients over 60 years of age, in patients taking corticosteroids and in patients who have had kidney, heart or lung transplants. In addition to age and corticosteroid use, other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disease such as rheumatoid arthritis. Tendonitis and tendon rupture also occur in patients using fluoroquinolones without these risk factors. Tendon ruptures can occur during or after the end of treatment; they have also been reported several months after the end of treatment. This product should be discontinued after a patient experiences tendon pain, swelling, inflammation, or rupture. After signs of tendonitis or tendon rupture, patients should be advised to rest and contact their physician to switch to a non-quinolone antibiotic medication. Patients with a history of tendon disease or who have experienced tendonitis and tendon rupture should avoid fluoroquinolone antibiotics, including moxifloxacin hydrochloride.
3. Exacerbation of myasthenia gravis
Fluoroquinolones, including moxifloxacin hydrochloride, have neuromuscular blocking activity and may exacerbate the symptoms of myasthenia gravis in patients with myasthenia gravis. Post-marketing serious adverse events, including death and the need for ventilatory support, have been associated with the use of fluoroquinolones in patients with myasthenia gravis. Moxifloxacin hydrochloride should be avoided in patients with myasthenia gravis.
4. Prolonged QT interval
Moxifloxacin hydrochloride has been shown to prolong the QT interval of the ECG in some patients. With 0.4 g of moxifloxacin hydrochloride administered orally, the mean QTc change from before administration to the time when moxifloxacin hydrochloride reached its maximum concentration was 6 msec (±26) (n=787). Intravenous drips of 0.4 g of moxifloxacin hydrochloride (daily drip duration of 1 hour) resulted in a mean QTc change of 10 msec (±22) (n=667) from before to day 1 of dosing and a mean QTc change of 7 msec (±24) (n=667) on day 3.
Due to the lack of experience with these patients, this product should be avoided in patients with
Known QT interval prolongation.
Ventricular arrhythmias, including the tip-twist type, as a prolonged QT interval may lead to an increased risk of these conditions.
Persistent arrhythmic conditions, such as clinically significant bradycardia and acute myocardial ischemia.
Untreated hypokalemia or hypomagnesemia.
Use of antiarrhythmic class IA drugs (e.g., quinidine, procainamide) or class III drugs (e.g., amiodarone, sotalol).
Other drugs that prolong the QT interval, such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants.
Elderly patients using injections of moxifloxacin hydrochloride may be more susceptible to drug-related prolongation of the QT interval.
Use in patients with mild, moderate or severe cirrhosis with metabolic disorders accompanied by hepatic insufficiency may result in prolongation of the QT interval. ECG should be monitored in patients with cirrhosis using moxifloxacin hydrochloride.
The degree of QT interval prolongation increases with increasing drug concentration or infusion rate of the injection, and therefore the recommended dose or titration rate should not be exceeded.
In premarketing clinical trials, the incidence of cardiovascular adverse events was similar in 798 patients using moxifloxacin hydrochloride and 702 control patients using concomitant drugs known to cause QT interval prolongation. In controlled clinical studies of more than 15,500 patients on moxifloxacin hydrochloride, including 759 patients who were hypokalemic at the start of treatment, there was no increase in cardiovascular morbidity or mortality due to QT interval prolongation. No increase in mortality was observed in 1 post-marketing observational study with moxifloxacin hydrochloride tablets in more than 18,000 patients, who were not tested with electrocardiograms.
5. Allergic reactions
Serious allergic reactions have been reported in patients using quinolones, including moxifloxacin hydrochloride. Some reactions occur in some patients after the first dose, and some may be accompanied by cardiovascular system failure, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and pruritus. Severe allergic reactions require emergency treatment with epinephrine. Moxifloxacin hydrochloride should be discontinued at the first sign of rash or any other signs of allergy. Oxygen administration, intravenous steroids, and airway management, including intubation, may be administered if necessary.
6. Other serious and potentially fatal reactions
Other serious and sometimes fatal events have been reported in patients using quinolones, including moxifloxacin hydrochloride. Some of these events are due to allergy and others are of unknown etiology. These events may be severe and usually occur after multiple doses of the drug are administered. Clinical manifestations may include one or more of the following: fever, rash, severe skin reactions (e.g., toxic epidermolysis bullosa, Stevens-Johnson syndrome); vasculitis; arthralgia; myalgia; serum sickness; allergic pneumonia; interstitial nephritis; acute renal insufficiency or renal failure; hepatitis, jaundice, acute hepatic necrosis, or hepatic failure; anemia, including hemolytic anemia and aplastic anemia; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; granulocyte deficiency; holocytopenia and/or other hematologic abnormalities.
The drug should be discontinued and action taken immediately upon the first appearance of rash, jaundice or any other allergic manifestation.
7. Central nervous system effects
The use of fluoroquinolones, including moxifloxacin hydrochloride, has been reported to increase the risk of CNS adverse reactions, including: convulsions and increased intracranial pressure (including pseudotumor cerebri) and toxic-induced psychosis. Use of fluoroquinolones may cause CNS reactions including agitation, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or behaviors. These reactions may occur after the first dose of the drug. If these reactions occur while the patient is on moxifloxacin hydrochloride, dosing should be discontinued and appropriate action taken. As with all fluoroquinolones, moxifloxacin hydrochloride should be administered when the benefits outweigh the risks in patients with known or suspected CNS disease (e.g., severe cerebral atherosclerosis, epilepsy) or in the presence of other risk factors (e.g., propensity for seizures or reduced seizure threshold).
8. Peripheral neuropathy
Rare sensory or sensorimotor axonal neuropathy affecting small and/or large axons, resulting in abnormal skin sensation, dullness of sensation, painful sensation to touch and debilitation have been reported in patients using fluoroquinolones, including moxifloxacin hydrochloride. In some patients, symptoms may occur soon after moxifloxacin hydrochloride administration and may be irreversible. If patients develop peripheral neuropathy symptoms, including pain, burning, tingling, numbness and/or weakness, or other sensory changes, including light touch, pain, warmth, position and vibration, the drug should be discontinued immediately. Fluoroquinolone antibiotics, including moxifloxacin hydrochloride, should be avoided in patients with a history of peripheral neuropathy.
9. Psychiatric reactions
Psychiatric reactions may occur even after the first use of quinolones (including moxifloxacin). In very rare cases, depressive or psychotic reactions that develop into suicidal ideation and self-harm behaviors, such as attempted suicide, have occurred. If a patient experiences these reactions, moxifloxacin should be discontinued and appropriate disease treatment should be instituted. Moxifloxacin should be used with caution in patients with psychiatric disorders or a history of psychotic disorders.
10. Clostridium difficile-associated diarrhea
Clostridium difficile-associated diarrhea (CDAD) has been reported with almost all antimicrobial drugs, including moxifloxacin hydrochloride, ranging in severity from mild diarrhea to severe colitis. Antimicrobial drug therapy alters the normal flora of the colon, leading to C. difficile overgrowth.
Toxins A and B, produced by C. difficile, are responsible for C. difficile-associated diarrhea. Highly virulent Clostridium difficile causes increased morbidity and mortality, and these infections are ineffective with antimicrobial therapy and may require colectomy. The possibility of CDAD should be considered in all cases of diarrhea after antibiotic therapy. Because CDAD may occur up to two months after treatment with antimicrobial agents, a careful history is necessary.
If C. difficile-associated diarrhea is suspected or confirmed, current antibiotics that do not target C. difficile may need to be discontinued. Appropriate fluid and electrolyte replacement, protein supplementation, treatment with antibiotics directed against C. difficile, and surgical evaluation should be performed when clinical indications arise.
11. Arthropathy in animals
Oral administration of moxifloxacin hydrochloride caused lameness in immature dogs. Histopathological examination of weight-bearing joints revealed permanent cartilage alterations in these dogs.
Related quinolones also produced cartilage erosion in weight-bearing joints as well as other joint symptoms in various immature animal species.
12. Interference with blood glucose
As with all fluoroquinolones, disturbances in blood glucose, including hyperglycemia and hypoglycemia, have been reported with moxifloxacin hydrochloride. In patients using moxifloxacin hydrochloride, blood glucose disturbances have occurred primarily in older patients who are also taking oral hypoglycemic agents (e.g., sulfonylureas) or using insulin. In diabetic patients, more attention needs to be paid to monitoring blood glucose. If hypoglycemia occurs, moxifloxacin hydrochloride needs to be discontinued immediately and appropriate treatment initiated.
13. Photosensitivity/phototoxicity
Moderate to severe photosensitivity/phototoxicity can occur after exposure to sunlight or UV radiation following the use of fluoroquinolone antibiotics, the latter may manifest as excessive sunburn reactions (e.g., burning sensation, erythema, blistering, oozing, edema), often at the site of exposure to light (usually the “V” area of the neck, the surface of the forearm extensors, the back of the hand). Therefore, overexposure to light sources should be avoided. The drug should be discontinued when phototoxic reactions occur.
14. Occurrence of bacterial drug resistance
In the absence of evidence of highly suspected bacterial infections or for the prevention of bacterial infections, the use of moxifloxacin hydrochloride does not benefit the patient, but rather increases the risk of the development of drug-resistant bacteria.
15. Effects on the ability to drive or operate machinery
No trials have been conducted on the effects of moxifloxacin hydrochloride on the ability to drive and operate machinery. However, fluoroquinolones, including moxifloxacin hydrochloride, may cause central nervous system reactions (e.g., dizziness, acute, transient blindness, see [ADVERSE REACTIONS]) or acute and short-lived loss of consciousness (syncope, see [ADVERSE REACTIONS]) that may impair the patient’s ability to drive or operate machinery. Patients should be advised to consider whether they are having a reaction to moxifloxacin hydrochloride before driving or operating machinery.
[For Pregnant and Lactating Women].
Pregnant women.
Pregnancy Category C.
Animal studies have shown moxifloxacin hydrochloride to be reproductively toxic, but the potential risk to humans is not known. The safety of moxifloxacin hydrochloride in humans during pregnancy has not been demonstrated, and the administration of quinolones in children can cause reversible joint damage. Therefore, moxifloxacin hydrochloride is contraindicated in women during pregnancy.
Nursing Women.
As with other quinolones, moxifloxacin hydrochloride can cause cartilage damage in weight-bearing joints in immature test animals. Preclinical studies have confirmed that small amounts of moxifloxacin hydrochloride can be distributed into human milk, and data are lacking in lactating women. Therefore, moxifloxacin hydrochloride is contraindicated in women who are breastfeeding.
Pediatric Dosage]
Moxifloxacin hydrochloride is contraindicated in children and adolescents (<18 years of age). The efficacy and safety of moxifloxacin hydrochloride in children and adolescents have not been established.
Geriatric Use]
Dose adjustment is not necessary for elderly patients.
The use of fluoroquinolones, such as moxifloxacin hydrochloride, in elderly patients increases the risk of serious tendon disease, including tendon rupture, and this risk is further increased when the patient is also receiving corticosteroid therapy. Tendonitis or tendon rupture can involve the Achilles tendon, hand, shoulder or other tendon locations and may occur during or after completion of treatment, and has been reported several months after treatment with fluoroquinolones. Caution should be exercised when prescribing to elderly patients, especially those on concomitant corticosteroids, and patients should be informed of this potential side effect and advised to discontinue moxifloxacin hydrochloride and contact their physician if any symptomatic tendonitis or tendon rupture occurs.
In a multi-dose controlled clinical trial, 23% of patients taking oral moxifloxacin hydrochloride were greater than or equal to 65 years of age and 9% were greater than or equal to 75 years of age. Clinical trial data demonstrated no difference in the safety and efficacy of oral moxifloxacin hydrochloride in elderly patients 65 years of age or older compared to the general adult population.
In trials of intravenous moxifloxacin hydrochloride, 42% of patients were 65 years of age and older and 23% were 75 years of age and older. Clinical trial data suggest that the safety of intravenous moxifloxacin hydrochloride in patients 65 years of age and older was consistent with that of the control group. Overall, older patients were more susceptible to the effects of medications associated with the QT interval. Therefore, moxifloxacin hydrochloride should be avoided in patients taking drugs that can cause prolongation of the QT interval (e.g., Class IA or Class III antiarrhythmic drugs) or in patients with risk factors for tip-twist ventricular tachycardia (e.g., known QT interval prolongation, uncorrected hypokalemia).
[Drug Interactions].
1. Antacids, aluminum thioglycollate, multivitamins and other products containing multivalent cations
Quinolones will bind to alkali metal and transition state metal cations in the form of chelates. Concomitant use of quinolones with oral antacids containing aluminum, magnesium, aluminum sulfate, or metal cations, or with multivitamins containing iron or zinc, or with prescriptions containing divalent and trivalent cations such as desoxynivalenol chewable/extended-release tablets or pediatric oral granules, may significantly impair their absorption, resulting in much lower than expected plasma concentrations of quinolones. Therefore, moxifloxacin hydrochloride tablets should be taken orally at least 4 hours before or 8 hours after the use of these drugs.
2. Warfarin
Quinolones, including moxifloxacin hydrochloride, have been reported to have enhanced anticoagulant effects of warfarin or its derivatives in patients. In addition, the infectious disease suffered by the patient and its accompanying inflammatory process, age and general status are risk factors for increased anticoagulant activity. Therefore, if quinolones are combined with warfarin or its derivatives, patients must be closely monitored for prothrombin time, international normalized ratio (INR), or other appropriate anticoagulation tests.
3. Antidiabetic drugs
Patients using both antidiabetic drugs and fluoroquinolones have reported disturbances in blood glucose, including hyperglycemia and hypoglycemia. Therefore, when the above drugs are used in combination, close monitoring of blood glucose is required, and if hypoglycemic reactions occur, moxifloxacin hydrochloride needs to be discontinued immediately and appropriate treatment carried out.
4.Non-steroidal anti-inflammatory drugs (NSAIDs)
Although no relevant conclusions were obtained in preclinical studies and clinical trials, the combination of quinolones and NSAIDs can increase the risk of central nervous system irritation and convulsions in patients.
5. Drugs that prolong the QT interval
Limited data suggest potential pharmacodynamic interactions when moxifloxacin hydrochloride is combined with other drugs that have a prolonging effect on the QT interval. The combination of the class III antiarrhythmic agent sotalol and high-dose moxifloxacin hydrochloride injection has been shown to have a further prolonging effect on the QT interval in dogs. Therefore, concomitant use of moxifloxacin hydrochloride with Class IA or Class III antiarrhythmic agents should be avoided.
[Drug overdose].
No serious adverse events have been observed with a single dose of oral administration up to 2.8g. In case of acute overdose, the stomach should be emptied and kept well hydrated. As it may cause prolongation of the QT interval in patients, cardiac monitoring should be performed and carefully observed, and patients should be given appropriate supportive therapy according to their clinical condition. Oral activated charcoal after drug overdose is effective in preventing increased overdose from moxifloxacin systemic exposure. Approximately 3% and 9% of moxifloxacin at 2% and 4.5% of glucuronide metabolites can be removed by continuous ambulatory peritoneal dialysis and hemodialysis, respectively.
Single oral doses of 2000 mg/kg, 500 mg/kg and 1500 mg/kg moxifloxacin hydrochloride resulted in death in rats, mice and crab-eating monkeys, respectively. Clinical manifestations include central nervous system (CNS) and digestive system symptoms such as decreased mobility, tremor, convulsions, vomiting and diarrhea.
Clinical trial】
1. Acute exacerbation of chronic bronchitis
A randomized, double-blind, controlled clinical trial conducted in the United States evaluated the treatment of acute exacerbations of chronic bronchitis with moxifloxacin hydrochloride tablets (400 mg once daily for 5 days). A total of 629 patients were enrolled in the study, which compared moxifloxacin hydrochloride tablets with clarithromycin tablets (500 mg twice daily for 10 days). The study evaluated the clinical cure rate from 7-17 days after administration. The clinical cure rate was 89% for moxifloxacin hydrochloride tablets (222/250) and 89% for clarithromycin tablets (224/251).
Table 5: Clinical cure rates of clinically evaluable patients by pathogenic organism at follow-up visits
(acute exacerbation of chronic bronchitis)
Pathogenic bacteria Moxifloxacin hydrochloride tablets Clarithromycin tablets Streptococcus pneumoniae 16/16 (100%) 20/23 (87%) Haemophilus influenzae 33/37 (89%) 36/41 (88%) Haemophilus parainfluenzae 16/16 (100%) 14/14 (100%) Catamoras 29/34 (85%) 24/24 (100%) Staphylococcus aureus 15/16 (94%) 6/8 (75%) Klebsiella pneumoniae 18/20 (90%) 10/11 (91%) Microbial killing and sterilization (killing + presumed killing) in the moxifloxacin hydrochloride treatment group was 100% for Streptococcus pneumoniae, 89% for Haemophilus influenzae, 100% for Haemophilus parainfluenzae, 85% for Catamorax, 94% for Staphylococcus aureus and 85%.
2. Community-acquired pneumonia
A randomized, double-blind, controlled clinical trial conducted in the United States compared the efficacy of moxifloxacin hydrochloride tablets (400 mg once daily) with high-dose clarithromycin tablets (500 mg twice daily) for the treatment of patients with community-acquired pneumonia as demonstrated by clinical and radiographic examination. A total of 474 patients were included in the study (382 of whom were suitable for inclusion in the efficacy analysis performed at the Day 14-35 follow-up visit). The clinical cure rates for clinically evaluable patients were 95% (184/194) and 95% (178/188) in the moxifloxacin hydrochloride tablet group and the high-dose clarithromycin tablet group, respectively.
A randomized, double-blind, controlled trial conducted in the United States and Canada compared the efficacy of moxifloxacin hydrochloride IV/PO sequential dosing (400 mg once daily for 7-14 days) with IV/PO fluoroquinolone controls (trevafloxacin or levofloxacin) for the treatment of patients with community-acquired pneumonia as demonstrated by clinical and radiographic examination. A total of 516 patients were included in the study (362 of whom were suitable for inclusion in the efficacy analysis performed at the post-treatment visit on days 7-30). Clinical cure rates were 86% (157/182) and 89% (161/180) in the moxifloxacin hydrochloride and fluoroquinolone control groups, respectively.
An open study conducted outside the United States enrolled 628 patients and compared moxifloxacin hydrochloride with amoxicillin/clavulanate IV/PO sequential administration (1.2 g IV every 8 hours/625 mg oral every 8 hours) alone or in combination with high-dose IV/PO clarithromycin (500 mg twice daily). The injectable formulation of the control drug was not approved by the FDA. On days 5-7 after administration, the clinical cure rate in the moxifloxacin hydrochloride group was 93% (241/258), which was better than amoxicillin/clavulanate ± clarithromycin (85%, 239/280) [95% confidence interval for the difference in cure rates between moxifloxacin and the control drug was (2.9%, 13.2%)]. At the post-treatment visit on days 21-28, the clinical cure rate in the moxifloxacin hydrochloride group was 84% (216/258), which was better than that of the control drug (74%, 208/280) [95% confidence interval for the difference in cure rates between moxifloxacin and the control drug was (2.6%, 16.3%)].
The clinical cure rates by pathogenic organism for the four community-acquired pneumonia (CAP) studies are shown in Table 6.
Table 6: Clinical cure rates by pathogenic organism (pooled data from CAP studies)
Pathogenic bacteria Moxifloxacin hydrochloride tablets Streptococcus pneumoniae 80/85 (94%) Staphylococcus aureus 17/20 (85%) Klebsiella pneumoniae 11/12 (92%) Haemophilus influenzae 56/61 (92%) Chlamydia pneumoniae 119/128 (93%) Mycoplasma pneumoniae 73/76 (96%) Catamorax 11/12 (92%) 3. by multidrug-resistant pneumonia Streptococcus (MDRSP) causing community-acquired pneumonia
Moxifloxacin hydrochloride was effective in the treatment of community-acquired pneumonia (CAP) caused by multidrug-resistant Streptococcus pneumoniae MDRSP* isolates. Of 37 microbiologically evaluable patients with MDRSP isolates, 35 patients (95%) achieved clinical and bacteriologic cure after treatment. The clinical and bacteriologic cure rates based on the number of treated patients are shown in Table 7.
*Multidrug-resistant Streptococcus pneumoniae (MDRSP) included isolates previously known to be penicillin-resistant Streptococcus pneumoniae (PRSP) and isolates resistant to two or more of the following antibiotics: penicillin (MIC ≥ 2 mcg/mL), second-generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and methotrexate/sulfamethoxazole.
Table 7: Clinical cure rates and bacteriological cure rates in patients treated with moxifloxacin hydrochloride for MDRSP CAP (population: suitable for efficacy analysis)
Susceptibility screening Clinical cure rate Bacteriological cure rate n/Na%n/Nb% Penicillin resistant 21/21100%c21/21100%cSecond generation cephalosporins resistant 25/2696%c25/2696%cMacrolide resistantd22/2396%22/2396%Methomethoprene/sulfamethoxazole resistant28/3093%28/3093%Tetracycline resistant 17/18 94%17/18 94% a) n=number of patients cured; N=number of patients with MDRSP (selected from a total of 37 patients)
b) n=number of patients cured (presumed killed or killed); N=number of patients with MDRSP (selected from a total of 37 patients)
c) One patient had a respiratory isolate resistant to penicillin and cefuroxime, but a blood isolate mediated to penicillin and cefuroxime. This patient was included in a database based on respiratory isolates.
(d) Azithromycin, clarithromycin and erythromycin were the macrolide antimicrobials tested.
Not all isolates were resistant to all classes of antimicrobials tested. Cure and kill rates are shown in Table 8.
Table 8: Clinical cure and bacterial kill rates of multidrug-resistant Streptococcus pneumoniae (community-acquired pneumonia)
Multidrug-resistant Streptococcus pneumoniae clinical cure rate bacterial kill rate 2 antimicrobial resistant 12/13 (92.3%) 12/13 (92.3%) 3 antimicrobial resistant 10/11 (90.9%)a 10/11 (90.9%)a 4 antimicrobial resistant 6/6 (100%) 6/6 (100%) 5 antimicrobial resistant 7/7 (100%)a 7/7 (100%)a (Bacteremia with multidrug-resistant Streptococcus pneumoniae9/9 (100%)9/9 (100%)a) One patient had a respiratory isolate resistant to 5 antimicrobials and a blood isolate resistant to 3 antimicrobials. The patient was included in the classification of resistant to 5 antimicrobials.
4. Acute bacterial sinusitis
A double-blind controlled study conducted in the United States compared moxifloxacin hydrochloride tablets (400 mg administered once daily for 10 days) with cefuroxime (250 mg administered twice daily for 10 days) for the treatment of acute bacterial sinusitis. The trial included 457 patients who were suitable for efficacy analysis. The clinical cure rates (cure + improvement) in the moxifloxacin hydrochloride tablet group and the cefuroxime group were 90% and 89%, respectively, at the cure test visit performed on days 7-21 after treatment.
A separate uncontrolled study was conducted to collect bacteriological data and evaluate the bacterial kill rate in adult patients treated with moxifloxacin hydrochloride tablets (400 mg administered once daily for 7 days). In this study, all patients underwent sinus puncture (n=336). The clinical cure and kill rates/probable kill rates for Streptococcus pneumoniae, C. catarrhalis, and Haemophilus influenzae at the follow-up visit performed on days 21-37 after treatment were 97% (29/30), 83% (15/18), and 80% (24/30), respectively.
5. Uncomplicated skin and skin tissue infections
A randomized, double-blind, controlled clinical trial conducted in the United States compared the efficacy of moxifloxacin hydrochloride (oral, 400 mg once daily for 7 days) with cefadroxil hydrochloride (oral, 500 mg three times daily for 7 days). In this study, 30% of patients were treated for uncomplicated abscesses, 8% for boils, 16% for cellulitis, 20% for impetigo, and 26% for other skin infections. Adjunctive procedures (incision and drainage or debridement) were performed in 17% and 14% of patients in the moxifloxacin hydrochloride group and control group, respectively. The clinical cure rates for evaluable patients in the moxifloxacin hydrochloride and cefadroxil HCl groups were 89% (108/122) and 91% (110/121), respectively.
6. Complex skin and skin tissue infections
Two randomized, active-controlled trials were conducted for complicated skin and skin structure infections (cSSSI). One double-blind trial, conducted primarily in North America, compared the efficacy of moxifloxacin hydrochloride IV/PO sequential dosing (400 mg once daily for 7-14 days) with the IV/PO control β-lactam/β-lactamase inhibitor for the treatment of patients with cSSSI. A total of 617 patients were included in the study, 335 of whom were suitable for efficacy analysis. Another international open study compared moxifloxacin hydrochloride (400 mg administered once daily for 7-21 days) with a control β-lactam/β-lactamase inhibitor IV/PO administered sequentially for the treatment of patients with cSSSI. A total of 804 patients were included in the study, of whom 632 were suitable for efficacy analysis. In these studies, 55% and 53% of patients in the moxifloxacin hydrochloride and control groups, respectively, underwent surgical incision, drainage or debridement, an adjuvant operation that constitutes a necessary part of the treatment for this indication. Healing rates varied with the type of diagnosis, from 61% in patients with infected ulcers to 90% in patients with concomitant dandruff. These cure rates were similar to those observed in the control group. The overall cure rates of evaluable patients and the clinical cure rates by pathogenic organism are shown in Tables 9 and 10.
Table 9: Overall clinical cure rates for patients with complicated skin and skin tissue infections
Study Moxifloxacin Hydrochloride
n/N (%) Control drug
n/N (%) 95% confidence interval* North America 125/162 (77.2%) 141/173 (81.5%) (-14.4%, 2%) International 254/315 (80.6%) 268/317 (84.5%) (-9.4%, 2.2%) * Difference in cure rate between moxifloxacin and control drug (moxifloxacin – control drug)
Table 10: Clinical cure rates of patients with complicated skin and skin tissue infections by pathogenic bacteria
Pathogenic organism Moxifloxacin Hydrochloride
n/N (%) Control drug
n/N (%) Staphylococcus aureus (methicillin-susceptible isolates)a106/129 (82.2%) 120/137 (87.6%) Escherichia coli 31/38 (81.6%) 28/33 (84.8%) Klebsiella pneumoniae 11/12 (91.7%) 7/10 (70%) Enterobacter cloacae 9/11 (81.8%) 4/7 ( 57.1%) Methicillin susceptibility measured only in North American studies
7. Complex intra-abdominal infections
Two randomized, active-controlled trials were conducted for complicated intra-abdominal infections. One double-blind trial, conducted primarily in North America, compared the efficacy of sequential moxifloxacin hydrochloride IV/PO administration (400 mg once daily for 5-14 days) with piperacillin/tazobactam administered intravenously followed by oral amoxicillin/clavulanic acid for the treatment of patients with complicated intra-abdominal infections (cIAI), including peritonitis, abscesses, appendicitis with perforation, and intestinal perforation . A total of 681 patients were included in the study, 379 of whom were considered clinically evaluable. Another international open study compared moxifloxacin hydrochloride (400 mg once daily for 5-14 days) with ceftriaxone administered intravenously + metronidazole administered intravenously followed by oral amoxicillin/clavulanic acid for the treatment of patients with cIAI. A total of 595 patients were included in the study, of whom 511 were considered clinically evaluable. The clinically evaluable population consisted of subjects with a surgically confirmed diagnosis of complicated infection, at least 5 days of dosing, and patients assessed at day 25-50 follow-up at the cure test visit. The overall clinical cure rates for the clinically evaluable subjects are shown in Table 11.
Table 11: Clinical cure rates for patients with complicated intra-abdominal infections
Study Moxifloxacin Hydrochloride
n/N (%) Control drug
n/N (%) 95% confidence interval* North America (total) 146/183 (79.8%) 153/196 (78.1%) (-7.4%, 9.3%) abscess 40/57 (70.2%) 49/63 (77.8%)aNAb non-abscess 106/126 (84.1%) 104/133 (78.2%) NA International (total) 199/246 (80.9%) 218/265 (82.3%) (-8.9%, 4.2%) abscess 73/93 (78.5%) 86/99 (86.9%) NA non-abscess 126/153 (82.4%) 132/166 (79.5%) NA* Difference in cure rate between moxifloxacin hydrochloride and control drug (moxifloxacin hydrochloride – control drug)
a) Exclusion of two patients who required additional surgery within the first 48 hours
b) NA-not applicable
8. Plague
For ethical and feasibility reasons, it was not possible to conduct an efficacy study of moxifloxacin hydrochloride in patients with pneumonic plague. Therefore, approval for this indication is based on an efficacy study conducted in an animal model and supporting pharmacokinetic data in adults and animals.
A randomized, blinded, placebo-controlled study was conducted using African green monkeys with pneumonic plague as the animal model. 20 African green monkeys (10 males and 10 females) inhaled a mean dose (± SD) of 100 ± 50 LD50 (range 92-127 LD50) of Yersinia pestis (strain CO92) aerosol. The minimum inhibitory concentration (MIC) of moxifloxacin against Yersinia pestis strain in this study is 0.06 mcg/mL. persistent fever for at least 4 hours will be treated with moxifloxacin or placebo given according to the human dosing regimen for 10 days. All study animals were febrile and developed bacteremia (Yersinia pestis) prior to the start of study dosing. Between 83-139 hours post-treatment (mean 115 ± 19 hours), 10/10 (100%) of animals receiving placebo died of disease. Within 30 days after the end of treatment, 10/10 (100%) animals in the moxifloxacin-treated group remained alive. Mortality was significantly lower in the moxifloxacin group compared to the placebo group (difference in survival: 100%, 95% exact confidence interval for two-sided test [66.3%, 100%], p < 0.0001).
In the African green monkey model of pneumonic plague, the improved survival of animals in the moxifloxacin group was statistically significant compared with the placebo group, and the mean plasma concentrations of moxifloxacin met or exceeded the plasma concentrations of the drug in adults on oral and intravenous dosing regimens. Mean (±SD) peak concentrations (Cmax) and total exposure (AUC) for adults dosed intravenously with 400 mg moxifloxacin were 3.9 ± 0.9 mcg/mL and 39.3 ± 8.6 mcg﹒h/mL, respectively. mean (±SD) peak concentrations of moxifloxacin in African green monkeys using a human dosing regimen mimicking human dosing (at a dose of 400 mg), one day after dosing and AUC0-24 were 4.4±1.5 mcg/mL and 22±8.0 mcg﹒h/mL, respectively.
Pharmacology and Toxicology
Pharmacological effects
(1) Mechanism of action
Moxifloxacin is an 8-methoxy fluoroquinolone antibacterial agent with broad-spectrum activity and bactericidal effect. Moxifloxacin has shown broad-spectrum antibacterial activity in vitro against Gram-positive, Gram-negative, anaerobic, acid-resistant bacteria and atypical microorganisms such as Mycoplasma, Chlamydia and Legionella.
The mechanism of bactericidal action is interference with topoisomerases II and IV, enzymes that control DNA topology and are critical in DNA replication, repair and transcription.
Moxifloxacin exhibits concentration-dependent bactericidal activity. The minimum bactericidal concentration and the minimum inhibitory concentration were essentially the same.
Moxifloxacin was also effective against β-lactam and macrolide resistant bacteria. The high in vivo activity of moxifloxacin was confirmed by experimental animal models of infection.
(2) Drug resistance
Resistance mechanisms leading to resistance to penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not affect the antibacterial activity of moxifloxacin. There was no cross-resistance between moxifloxacin and these antimicrobials. No plasmid-mediated resistance has been observed to occur to date.
The 8-methoxy fraction of moxifloxacin has high activity against Gram-positive bacteria and low selectivity for drug resistance mutations compared to the 8-hydrogen fraction. The bulky 7-position diazepine substituent prevents active exocytosis, which is the mechanism of resistance to fluoroquinolones.
In vitro tests showed that resistance to moxifloxacin emerged slowly only after a multi-step mutation. In conclusion its resistance rate is very low (10-7-10-10). Sequential exposure of bacteria to concentrations below the moxifloxacin MIC resulted in only a small increase in MIC values.
Cross-resistance exists with other quinolones. However, some Gram-positive and anaerobic bacteria that are resistant to other quinolones are sensitive to moxifloxacin.
(3) Effects on human intestinal flora
The following changes were observed in two studies of volunteers receiving moxifloxacin hydrochloride orally: decreases in Escherichia coli, Bacillus spp., Proteus spp., Enterococcus spp., Klebsiella spp. and anaerobic bacteria (such as Bifidobacterium, Eubacterium and Streptococcus digestiveis), which could return to normal within two weeks, and no Clostridium difficile toxin was detected.
(4) In vitro test sensitivity data
Sensitive Moderately sensitive drug-resistant Gram-positive bacteria Gardia vaginalis Streptococcus pneumoniae, including multi-drug-resistant Streptococcus pneumoniae strains [MDRSP], including known penicillin-resistant strains (PRSP), and strains resistant to two or more of the following antibiotics: penicillin (MIC ≥ 2 μg/mL), second-generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, methamphetamine sulfamethoxazole/sulfamethoxazole.  Group A Streptococcus pyogenes* Streptococcus mydriasis Streptococcus lactis-free Streptococcus lactis-stop Streptococcus pharyngitis* Streptococcus constellatus* Staphylococcus aureus (including methicillin-sensitive strains)* Staphylococcus aureus (methicillin/oxifloxacin-resistant strains)+ Staphylococcus coccoides Staphylococcus epidermidis (including methicillin-sensitive strains)Staphylococcus epidermidis (methicillin/oxifloxacin-resistant strains)+ Staphylococcus haemolyticus Staphylococcus humanus Staphylococcus saprophyticus Staphylococcus mimicus Corynebacterium diphtheriae Enterococcus faecalis* (vancomycin, gentamicin-sensitive strains only) */** proven to be effective against approved clinical indications caused by sensitive bacteria
+Moxifloxacin only has in vitro MIC values within its sensitivity range for methicillin-resistant staphylococci mediated by the MecA gene. Therefore, if such strains are found moxifloxacin is not recommended.
Sensitive Moderately Sensitive Drug-resistant Gram-negative Bacteria Haemophilus influenzae (both beta-lactamase-producing and non-beta-lactamase-producing strains)* Haemophilus parainfluenzae* Catamorax (both beta-lactamase-producing and non-beta-lactamase-producing strains)* Bordetella pertussis Escherichia coli* Klebsiella pneumoniae* Klebsiella pneumoniae Enterobacter aerogenes Enterobacter glutamicum* Enterobacter intermedius Enterobacter sakazakii Pseudomonas aeruginosa  Pseudomonas fluorescens Pseudomonas oxytoca Burkholderia maltophilia Oligotrophomonas oxytoca* Aspergillus oryzae Morganella niger** Prevotella spp.
Sensitive Moderately sensitive Drug-resistant anaerobic bacillus G. aeruginosa E. fragilis* Ovomycetes Clostridium polymorphicum* Monomorphic Clostridium spp. Streptococcus spp. Digestive Streptococcus* Porphyromonas spp. Anaerobic Porphyromonas non-dissociated Porphyromonas macroporphyromonas Prevotella spp. Propionibacterium spp. Clostridium perfringens* Clostridium multilocularis Other Chlamydia pneumoniae* Chlamydia trachomatis** Mycoplasma pneumoniae* Human (type) Mycoplasma mycoplasma (plasmodium) Legionella pneumophila* Coxiella burgdorferi */** Proven to be effective against approved clinical indications caused by sensitive bacteria
Rates of acquired resistance for certain bacteria may vary with geography and time. Localized resistance is possible, especially when treating severe infections. The results of the in vitro susceptibility testing described above can be used as a guide to determine if the microorganism is susceptible to moxifloxacin.
PK/PD comparison of single doses of intravenous and oral administration of 0.4 g moxifloxacin hydrochloride.
An AUC/MIC90 value greater than 125 and a Cmax/MIC90 of 8-10 in patients requiring hospitalization is the expected value for clinical cure. Outpatients usually have lower parameter values with AUC/MIC90 greater than 30-40.
The following table compares the calculated values of PK/PD for a single dose of intravenous and oral administration of 0.4 g moxifloxacin hydrochloride.
Mode of administration intravenous oral parameters (median) AUIC[h] Cmax/MIC90 a) AUIC[h] Cmax/MIC90MIC90
0.125 mg/L 313 32.5 279 23.6 MIC90
0.25mg/L 156 16.2 140 11.8 MIC90
0.5mg/L 78 8.1 70 5.9 a) 1h infusion
Toxicological study
The target organs of toxicity for moxifloxacin hydrochloride, as for other quinolones, were the hematological system (bone marrow cytopenia in dogs and monkeys), the central nervous system (convulsions in monkeys), and the liver (elevated liver enzymes and monocytic necrosis in rats, dogs, and monkeys), and these changes occurred after high doses or long-term administration of moxifloxacin hydrochloride.
In a local tolerance study in dogs, no signs of local intolerance were observed after intravenous moxifloxacin hydrochloride administration. Inflammatory changes were seen in the soft tissues surrounding the arteries after intra-arterial administration, suggesting that intra-arterial administration of moxifloxacin hydrochloride should be avoided.
Genotoxicity
Four strains (TA1535, TA1537, TA98 and TA100) were negative in the Ames test, as were the mutation test in Chinese hamster ovary HPRT and the UDS test in rat primary hepatocytes. As with other quinolones, moxifloxacin hydrochloride was positive for TA102 in the Ames test, probably due to its inhibition of topoisomerase. In vitro tests showed that high doses of moxifloxacin (300 μg/ml) caused chromosomal abnormalities in V79 cells of Chinese hamsters, however, in vivo micronucleus tests in mice showed negative results. In addition, the in vivo test was negative for dominant lethality in mice. In conclusion, the results of the in vivo test adequately reflect its genotoxicity in vivo.
Reproductive toxicity
Reproductive toxicity studies in rats, rabbits and monkeys have shown that moxifloxacin hydrochloride can pass through the placenta. Studies in rats (administered orally and intravenously) and monkeys (administered orally) showed no teratogenic effects or impairment of fertility following administration of moxifloxacin. Skeletal deformities were observed in rabbits administered intravenously at 20 mg/kg. The results of this study are consistent with the known effects of quinolones on skeletal development. At human therapeutic concentrations, the incidence of abortion was increased in monkeys and rabbits. In rats, when administered orally at doses 63 times the maximum recommended drug dose (at mg/kg body weight) to bring blood concentrations within the human therapeutic dose range, decreased fetal rat body weight, increased abortions, mildly prolonged gestation, and increased spontaneous activity in some female and male pups were observed.
Carcinogenicity
Although routine long-term studies on the carcinogenic effects of moxifloxacin hydrochloride have not been conducted, the drug has been tested for genotoxicity in vitro and in vivo. In addition, an accelerated carcinogenicity test (carcinogenicity/carcinogenicity test) was conducted in rats for humans. No evidence of carcinogenicity was found in the rat carcinogenicity/carcinogenicity assay.
Phototoxicity
Moxifloxacin hydrochloride is stable to light and has low potential phototoxicity. In vitro and animal studies have shown that moxifloxacin hydrochloride is less phototoxic than other quinolones. The photocarcinogenic effect of UV light was increased in mice given a number of quinolones and exposed to UV light. No photocarcinogenic studies have been conducted with moxifloxacin hydrochloride, and no potential phototoxicity of moxifloxacin hydrochloride was confirmed in a phase I study in volunteers.
Electrocardiogram
High concentrations of moxifloxacin hydrochloride have an inhibitory effect on delayed rectifier potassium currents in the heart, thus leading to prolongation of the QT interval. Toxicological studies in dogs given orally >90 mg/kg moxifloxacin resulted in blood concentrations >16 mg/L, causing prolongation of the QT interval, but no arrhythmias. Reversible non-fatal ventricular arrhythmias were seen only when cumulative intravenous administration above 50 times the human dose (>0.3 g/kg) resulted in blood concentrations ≥0.2 g/L (30 times higher than the therapeutic intravenous concentration).
Ocular toxicity
Ocular toxicity was not seen in repeated 6-month toxicity tests in rats and monkeys. In canine tests, plasma concentrations ≥20 mg/L at high doses (≥60 mg/kg) administered caused changes in the retinal current map and retinal atrophy in individual animals.
Arthrotoxicity
Quinolones are known to cause lesions in the cartilage of weight-bearing joints in immature laboratory animals. The minimum oral dose of moxifloxacin hydrochloride, which can cause joint toxicity in young dogs, is 4 times the recommended maximum therapeutic dose (0.4 g/50 kg human body weight), and its blood concentration is 2-3 times higher than that at the recommended therapeutic dose.
Pharmacokinetics
1. Absorption, distribution, metabolism, excretion
Absorption
Moxifloxacin tablets are well absorbed in the gastrointestinal tract after oral administration. The absolute bioavailability of moxifloxacin is about 90%.
The absorption of moxifloxacin is not affected when moxifloxacin is taken with a high-fat meal (i.e., 500 calories in fat).
Moxifloxacin does not significantly affect the degree of systemic absorption or the absorption rate (AUC) when taken with 1 cup of yogurt.
Table 12: Cmax and AUC means (± standard deviation) after single or multiple oral doses of 400 mg moxifloxacin
 Cmax (mg/L) AUC (mg h/L) Half-life (h) Single oral administration Healthy volunteers (n=372) 3.1±136.1±9.111.5-15.6a Multiple oral administration Healthy young male/female volunteers (n=15) 4.5±0.548±2.712.7±1.9 Healthy elderly male volunteers (n=8) 3.8±0.351.8±6.7 Healthy older female volunteers (n=8) 4.6±0.654.6±6.7 Healthy young male volunteers (n=8) 3.6±0.548.2±9 Healthy young female volunteers (n=9) 4.2±0.549.3±9.5 a) Range of mean values across studies
Table 13: Mean Cmax and AUC (± standard deviation) after single or multiple 1-hour intravenous doses of 400 mg moxifloxacin
 Cmax (mg/L) AUC (mg h/L) Half-life (h) Single IV dose Healthy young male/female volunteers (n=56) 3.9±0.939.3±8.68.2-15.4a Patients (n=118) Male (n=64) 4.4±3.7 Female (n=54) 4.5±2 <65 years (n=58) 4.6± 4.2 ≥65 years (n=60) 4.3±1.3 Multiple intravenous dosing Healthy young male volunteers (n=8) 4.2±0.838±4.714.8±2.2 Healthy older volunteers (n=12; 8 males, 4 females) 6.1±1.348.2±0.910.1±1.6 Patientsb (n=107) Males (n=58) 4.2 ±2.6 Female (n=49) 4.6±1.5 <65 years (n=52) 4.1±1.4 ≥65 years (n=55) 4.7±2.7 a) Range of mean values across studies
b) Expected Cmax (concentration obtained at the end of titration)
Within the range of the highest donor dose (single oral dose of 1200 mg), blood concentrations increased in proportion to the dose. The mean time (± standard deviation) of the plasma elimination half-life was 12 ± 1.3 hours; steady state was reached after at least 3 days when 400 mg was administered once daily.
Figure 1: Mean steady-state blood concentrations obtained when moxifloxacin hydrochloride was administered once daily at 400 mg orally (n=10) or intravenously at 400 mg (n=12)
Distribution
The binding of moxifloxacin to serum proteins was approximately 30-50% and did not correlate with drug concentration. The volume of distribution of moxifloxacin ranged from 1.7-2.7 L/kg. Moxifloxacin is widely distributed in the body and tissue concentrations usually exceed blood concentrations. Moxifloxacin has been detected in saliva, nasal and bronchial secretions, sinus mucosa, skin blister fluid, subcutaneous tissue, skeletal muscle, and abdominal tissue and body fluids following oral or intravenous doses of 400 mg moxifloxacin. A summary of moxifloxacin concentrations measured in various tissues and body fluids following oral or intravenous administration of 400 mg of moxifloxacin is shown in Table 14. the rate of elimination of moxifloxacin from tissues is generally similar to the rate of plasma elimination.
Table 14: Tissue concentrations of moxifloxacin after a single oral or intravenous dose of 400 mg (mean ± standard deviation)
and corresponding blood concentrations
Tissue and body fluid N Blood concentration (mcg/mL) Tissue and body fluid concentration (mcg/mL or (mcg/g) Tissue-plasma ratio Respiratory system Alveolar macrophages 53.3±0.761.8±27.321.2±10 Bronchial mucosa 83.3±0.75.5±1.31.7±0.3 Epithelial cell lining 53.3±0.724.4± 14.78.7±6.1 sinus maxillary sinus mucosa 43.7±1.1b7.6±1.72±0.3 anterior sieve mucosa 33.7±1.1b8.8±4.32.2±0.6 nasal polyps 43.7±1.1b9.8±4.52.6±0.6 skin, musculoskeletal blistering fluid5 3±0.5c2.6±0.90.9±0.2 subcutaneous tissue 62.3±0.4d0.9±0.3e0.4±0.6 Skeletal muscle 62.3±0.4d0.9±0.2e0.4±0.1 Abdominal cavity abdominal tissue 82.9±0.57.6±22.7±0.8 Abdominal exudate 102.3±0.53.5±1.21.6±0.7 Pus 62.7±0.72.3±1.50.8±0.4 a) All concentrations of moxifloxacin were determined 3 hours after a single 400 mg dose; except for abdominal tissue and exudate concentrations, which were determined 2 hours after dosing, and sinus concentrations, which were determined 3 hours after dosing on day 5.
b) N=5
c) N=7
d) N=12
e) Reflects only the non-protein bound concentration of the drug.
Metabolism
Approximately 52% of the oral dose or intravenously administered dose is metabolized as glucosinolate and sulfate bound. The cytochrome P450 system is not involved in the metabolism of moxifloxacin and is unaffected by moxifloxacin. The sulfate conjugate (M1) accounts for 38% of the moxifloxacin administered dose and is excreted primarily in the feces. Approximately 14% of the oral dose or intravenously administered dose is converted to glucosinolate conjugate (M2) and excreted in the urine.The peak blood concentration of M2 is approximately 40% of the parent drug, whereas the blood concentration of M1 is usually less than 10% of the moxifloxacin concentration.
In vitro studies of cytochrome (CYP) P450 enzymes have shown that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2.
Excretion
Approximately 45% of the oral dose and intravenously administered dose of moxifloxacin is excreted as a prototype drug (approximately 20% in urine and 25% in feces). A total of 96% ± 4% of the oral dose was excreted as the prototype drug or as a known metabolite. The mean (± standard deviation) of apparent overall and renal clearance was 12 ± 2 L/h and 2.6 ± 0.5 L/h, respectively.
2. Pharmacokinetics for specific populations
Older adults
No age-related changes in the pharmacokinetics of moxifloxacin were observed in 16 healthy elderly volunteers (8 men; 8 women) and 17 young healthy volunteers (8 men; 9 women) after 10 consecutive days of oral administration of 400 mg moxifloxacin. 16 healthy male volunteers (8 young; 8 elderly) received a single oral dose of 200 mg moxifloxacin, and the difference between young and No statistical differences in systemic exposure (AUC and Cmax) were observed in the elderly, and the elimination half-life remained unchanged.
No dose adjustment based on age was required. In large phase III studies, following an intravenous dose of 400 mg moxifloxacin, concentrations observed at the end of the dose in elderly patients were similar to those observed in younger patients.
Children
Pharmacokinetic studies of moxifloxacin in pediatric subjects have not been performed.
Gender
In 23 healthy male subjects (19-75 years of age) and 24 healthy female subjects (19-70 years of age) given 400 mg of moxifloxacin orally once daily, the mean AUC and Cmax were 8% and 16% higher, respectively, in female subjects than in male subjects after 10 days of continuous dosing. When weight differences were considered, no significant differences in moxifloxacin pharmacokinetics were seen between male and female subjects.
A single dose 400 mg study was conducted in 18 young females and males. Pharmacokinetic comparisons of moxifloxacin in this study (9 young females and 9 young males) showed no differences in AUC or Cmax due to gender. No dose adjustment based on gender was required.
Race
Following a once daily oral dose of 400 mg moxifloxacin, steady-state pharmacokinetics of moxifloxacin in Japanese male subjects were similar to those in Caucasians with a mean Cmax of 4.1 mcg/mL, an AUC24 of 47 mcg﹒h/mL, and an elimination half-life of 14 hours.
Renal insufficiency
No significant changes in the pharmacokinetic parameters of moxifloxacin were observed in mild, moderate, severe or end-stage renal disease. No dose adjustment is required in patients with renal impairment, including those requiring hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).
In a single oral dosing study in 24 patients with normal to severely impaired renal function, mean peak concentrations (Cmax) of moxifloxacin were reduced by 21% and 28% in patients with moderate (CLCR ≥30 and ≤60 mL/min) and severe (CLCR <30 mL/min) renal impairment, respectively. The mean systemic exposure (AUC) was increased by 13% in these patients. In patients with moderate and severe renal impairment, the mean AUC increased 1.7-fold (up to 2.8-fold) for sulfate conjugates (M1) and 2.8-fold (up to 4.8-fold) and 1.4-fold (up to 2.5-fold) for glucosinolate conjugates (M2), respectively.
Single and multiple doses of moxifloxacin were administered to hemodialysis patients with CLCR <20 mL/min or continuous ambulatory peritoneal dialysis patients (8 hemodialysis patients and 8 continuous ambulatory peritoneal dialysis patients) to study pharmacokinetics. After a single oral dose of 400 mg moxifloxacin, the AUC of these hemodialysis and continuous ambulatory peritoneal dialysis patients did not change significantly compared to the AUC normally observed in healthy volunteers. Moxifloxacin Cmax values in hemodialysis and continuous ambulatory peritoneal dialysis patients were approximately 45% and 33% lower, respectively, compared to historical controls in healthy volunteers. These patients had a 1.4-1.5-fold increase in sulfate conjugate (M1) exposure (AUC). The mean AUC of the glucosinolate conjugate (M2) increased 7.5-fold compared to healthy subjects, while the mean Cmax values increased 2.5-3-fold. The sulfate and glucosinolate conjugates of moxifloxacin are not biologically active, and the clinical significance of increased exposure to these metabolites in patients with renal disease, including those on hemodialysis and continuous ambulatory peritoneal dialysis, has not been studied.
The mean systemic exposure (AUCss) to moxifloxacin after 7 days of once-daily oral dosing of 400 mg moxifloxacin hydrochloride in hemodialysis patients or continuous ambulatory peritoneal dialysis patients was similar to the mean systemic exposure typically observed in healthy volunteers. Steady-state Cmax values were about 22% lower in hemodialysis patients than in continuous ambulatory peritoneal dialysis patients, but the latter were comparable to healthy volunteers. Only small amounts of moxifloxacin were excreted from the body in hemodialysis and continuous ambulatory peritoneal dialysis, about 9% and 3%, respectively. Hemodialysis and continuous ambulatory peritoneal dialysis excreted about 4% and 2% of glucosinolate metabolites (M2), respectively.
Hepatic insufficiency
Mild and moderate hepatic insufficiency (Child Pugh class A and B) do not require dose adjustment. However, metabolic disturbances associated with hepatic insufficiency may cause prolongation of the QT interval and the product should be used with caution in these patients.
After a single oral dose of 400 mg moxifloxacin in 6 patients with mild hepatic insufficiency (Child Pugh class A) and 10 patients with moderate hepatic insufficiency (Child Pugh class B), the mean systemic exposure (AUC) of moxifloxacin was 78% and 102% of that of 18 healthy controls, respectively, and the mean peak concentration (Cmax) was 79% and 84% of that of controls, respectively.
The mean AUC of moxifloxacin sulfate conjugates increased by 3.9-fold (up to 5.9-fold) and 5.7-fold (up to 8-fold) in the mild and moderate hepatic insufficiency groups, respectively. The mean M1 Cmax increased about 3-fold (up to 4.7-fold and 3.9-fold) in both groups. The mean AUC of moxifloxacin glucosinolate conjugate (M2) increased by 1.5-fold (up to 2.5-fold) in both groups. the mean Cmax of M2 increased by 1.6-fold and 1.3-fold (up to 2.7-fold and 2.1-fold), respectively. The clinical significance of increased exposure to sulfate and glucosinolate conjugates has not been studied. In some patients participating in clinical trials, the blood concentrations of moxifloxacin and its metabolites measured around the time of moxifloxacin peak after the first intravenous drip or oral dose of this product in Child Pugh Class C patients (n=10) were similar to those in Child Pugh Class A/B patients (n=5); in addition, they were also similar to those observed in studies in healthy volunteers.
Potential photosensitivity
A study of skin reactions induced by ultraviolet (UVA and UVB) and visible light radiation was conducted in 32 healthy volunteers (8 per group). This study confirmed that this product did not show phototoxicity compared to placebo. The minimal erythema dose (MED) was measured before and after administration of this product (200 mg or 400 mg once daily), lomefloxacin (400 mg once daily), or placebo. In this study, the minimum erythematous dose measured for both doses of this product was not significantly different compared to placebo, while lomefloxacin significantly reduced the minimum erythematous dose.
It is difficult to determine the cause of relative photosensitivity/phototoxicity among the various different fluoroquinolones during actual patient use because other factors also play an important role in determining whether subjects are susceptible to this adverse event: the patient’s skin pigmentation, frequency and duration of sun exposure and artificial UV exposure, application of sunscreen and wearing protective clothing, concomitant use of other medications, fluoroquinolone The dosage and duration of fluoroquinolones.
3. Drug-drug interactions
The following drug-drug interactions have been studied in healthy volunteers or patients.
As observed with other quinolones, antacids and iron significantly reduced the bioavailability of moxifloxacin.
Calcium, digoxin, itraconazole, morphine, probenecid, ranitidine, theophylline and warfarin do not significantly affect the pharmacokinetics of moxifloxacin. These results and data from in vitro studies suggest that moxifloxacin may not significantly alter the metabolic clearance of drugs metabolized by CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2 enzymes.
Moxifloxacin does not have clinically significant effects on the pharmacokinetics of atenolol, digoxin, glibenclamide, itraconazole, oral contraceptives, theophylline, cyclosporine, and warfarin.
Antacids
The mean AUC of moxifloxacin was reduced by 26%, 60%, and 23% in 12 healthy volunteers when moxifloxacin (single oral 400 mg tablet) was administered orally 2 hours before, concomitantly with, or 4 hours after the administration of an aluminum/magnesium-containing antacid (900 mg aluminum hydroxide and 600 mg magnesium hydroxide as a single oral dose). Moxifloxacin tablets should be taken at least 4 hours before or 8 hours after taking antacids containing magnesium or aluminum, aluminum thioglycollate, metal cations (e.g., iron), and zinc-containing multivitamin preparations or dehydroinosine chewable/extended-release tablets or pediatric oral granules.
Atenolol
In a crossover study that included 24 healthy volunteers (12 men; 12 women), the mean AUC of atenolol following a single oral dose of 50 mg of atenolol administered in combination with placebo was similar to the mean AUC observed with a single oral dose of 400 mg of moxifloxacin administered in combination with atenolol. The mean Cmax of single-dose atenolol was reduced by about 10% after coadministration of a single dose of moxifloxacin.
Calcium
Twelve healthy volunteers were concomitantly given moxifloxacin (400 mg single-dose administration) and calcium (500 mg Ca++ dietary supplement single-dose administration), followed by two additional doses of calcium 12 and 24 hours after moxifloxacin administration. Calcium did not have any significant effect on the mean AUC of moxifloxacin. The mean Cmax of moxifloxacin co-administered with calcium was slightly lower than that of moxifloxacin alone, while the time to peak blood concentration was slightly longer than that of moxifloxacin alone (2.5 hours and 0.9 hours, respectively). These differences were not considered to be clinically significant.
Digoxin
In a study that included 12 healthy volunteers, no significant effect of moxifloxacin (400 mg once daily for 2 days) on the AUC of digoxin (0.6 mg administered as a single dose) was seen. The mean Cmax of digoxin increased by about 50% during the digoxin distribution phase. The abrupt increase in digoxin Cmax was not considered clinically significant. The pharmacokinetics of moxifloxacin were similar when moxifloxacin was administered in combination with digoxin or when moxifloxacin was administered alone. No dose adjustment of moxifloxacin or digoxin is required when moxifloxacin is administered concomitantly with digoxin.
Glibenclamide
In patients with diabetes mellitus, the mean AUC and Cmax of glibenclamide (2.5 mg once daily for two weeks as pretreatment; followed by 5 consecutive days of combined dosing) were 12% and 21% lower, respectively, than those of glibenclamide combined with placebo when administered in combination with moxifloxacin (400 mg once daily for 5 days). However, patients receiving glibenclamide combined with moxifloxacin administration had slightly lower blood glucose levels compared with those receiving glibenclamide alone, indicating that moxifloxacin did not interfere with glibenclamide activity. The results of these interactions are not considered clinically significant.
Iron
The mean AUC and Cmax of moxifloxacin were reduced by 39% and 59%, respectively, when moxifloxacin tablets were co-administered with iron (ferrous sulfate 100 mg once daily for two days). Therefore, this product should be administered 4 hours before or 8 hours after the administration of iron preparations.
Itraconazole
In a study that included 11 healthy volunteers, no significant effect of itraconazole (a potent inhibitor of CYP450 enzyme 3A4, 200 mg once daily for 9 days) on the pharmacokinetics of moxifloxacin (400 mg moxifloxacin given as a single dose on day 7 of itraconazole administration) was seen. In addition, studies have shown that moxifloxacin does not affect the pharmacokinetics of itraconazole.
Morphine.
In a study that included 20 healthy male and female volunteers, no significant effect of morphine sulfate (single intramuscular injection of 10 mg) on the mean AUC and Cmax of moxifloxacin (400 mg single dose) was observed.
Oral contraceptives
A placebo-controlled study enrolling 29 healthy female subjects showed that 400 mg moxifloxacin, administered once daily for 7 days, did not interfere with the hormonal suppression (as measured by serum progesterone, FSH, estradiol and LH) or interfere with the pharmacokinetics of oral contraceptives containing 0.15 mg levonorgestrel/0.03 mg ethinyl estradiol.
Propofol
In a study enrolling 12 healthy volunteers, probenecid (500 mg twice daily for 2 days) did not alter the renal clearance of moxifloxacin (400 mg single dose) or the total amount of moxifloxacin excreted via the kidney.
Ranitidine.
In a study that included 10 healthy volunteers, no significant effect of ranitidine (150 mg twice daily for 3 days as pretreatment) on the pharmacokinetics of moxifloxacin (400 mg single dose) was seen.
Theophylline
In a study that included 12 healthy volunteers, no significant effect of moxifloxacin (200 mg once every 12 hours for 3 days) on the pharmacokinetics of theophylline (400 mg once every 12 hours for 3 days) was seen. In addition, studies have shown that theophylline does not affect the pharmacokinetics of moxifloxacin. the effect of 400 mg moxifloxacin in combination with theophylline has not been studied.
Warfarin
In a study that included 24 healthy volunteers, no significant effect of moxifloxacin (400 mg once daily for 8 days) on the pharmacokinetics of R- and S-warfarin (25 mg warfarin sodium given as a single dose on day 5) was seen. No significant changes in prothrombin time were observed.
4. Pharmacokinetic study in Chinese population
Single dose administration: 10 healthy subjects were randomly divided into 3 groups (3 in the first group, 3 in the second group, and 4 in the third group) according to the Latin formula design, and 0.2g, 0.3g, and 0.4g moxifloxacin were cross-administered, all infused over 90 minutes, with an interval of 7 days between each trial. (Note: The infusion time of moxifloxacin hydrochloride sodium chloride injection abroad ranged from 30-60 minutes. The infusion time of moxifloxacin hydrochloride sodium injection in the trial was calculated to be 90 minutes based on the infusion rate tolerated by the heart in healthy Chinese subjects.)
The obtained drug-time curves all fit the two-atrial model better. The specific parameters were as follows.
 Cmax (mg/L) AUC0-96 (mg*h/L) Dose ratio Cmax ratio AUC0-96 ratio 0.2g2.528±0.19132.642±2.7541:1.5:21:1.5:2.051:1.48:20.3g3.782±0.33348.433±3.227 0.4g5.178± 0.17665.189±4.965 Multiple dose administration: 10 healthy subjects received 0.4g of moxifloxacin intravenously once daily for 10 days of infusion.
Blood concentrations reached steady state on approximately day 4. The mean peak concentration after reaching steady state was 5.351±0.533 mg/L and the mean trough concentration was 1.084±0.177 mg/L, with a calculated fluctuation factor of 1.39. The AUCss 0-24 after steady state was not significantly different from the AUC0-∞ after the first dose. The half-life was about 14 hours, indicating no accumulation of the drug in the body after 10 days of continuous administration.
Compared with the results of pharmacokinetic tests in Chinese and foreign literature, there are differences in peak concentrations, which are mainly due to the different rates of intravenous infusion, while the distribution and elimination processes of the drug are basically the same.
Storage】Store under 25℃ in a tightly sealed place under shade.
Package】Packaged in PVC/PVDC aluminum plastic, 6 tablets/plate/box.
Expiration date】36 months.
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Company Name: Guangdong Dongyang Pharmaceutical Co.
Production Address: North Industrial Zone, Songshan Lake Science and Technology Industrial Park, Dongguan City, Guangdong Province
Manufacturer
Company Name: Guangdong Dongyang Pharmaceutical Co.
Production Address: North Industrial Zone, Songshan Lake Science and Technology Industrial Park, Dongguan City, Guangdong Province
Postal Code: 523808
Sales telephone number: 0769-85370280 Fax number: 0769-85370206
Medical consultation telephone number: 4006707855
Web
Address: http://pharm.hec.cn/
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