Instructions for use Moxifloxacin tablets 400 mg No. 5
Composition
active ingredient: moxifloxacin;
1 tablet contains 436.8 mg of moxifloxacin hydrochloride, which corresponds to 400 mg of moxifloxacin;
excipients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, hypromellose, red iron oxide (E 172), macrogol 4000, titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, elongated in shape, pink in color, with convex upper and lower surfaces.
Pharmacotherapeutic group
Antimicrobials for systemic use. Antibacterials for systemic use. Antibacterials from the quinolone group. Fluoroquinolones. Moxifloxacin. ATX code J01M A14.
Pharmacological properties
Pharmacodynamics
Mechanism of action.
Moxifloxacin is an 8-methoxyfluoroquinolone with a broad spectrum of bactericidal activity. In vitro, moxifloxacin is effective against many gram-positive and gram-negative microorganisms.
Moxifloxacin has been shown to be effective against bacteria resistant to β-lactam and macrolide drugs.
The bactericidal effect of moxifloxacin is due to inhibition of both types of topoisomerase II (DNA gyrase and topoisomerase IV), which are necessary for the replication, transcription and repair of bacterial DNA.
The C8-methoxy residue is believed to contribute to improved activity and attenuate the selection of resistant mutants in Gram-positive bacteria compared to the C8-H residue. The presence of a large dicycloamine residue at the C-7 position prevents active efflux associated with the norA or pmrA genes found in some Gram-positive bacteria.
Moxifloxacin has concentration-dependent bactericidal activity. Minimum bactericidal concentrations (MBCs) generally correspond to minimum inhibitory concentrations (MICs).
Impact on intestinal flora in humans
In two studies in volunteers, the following changes in the intestinal flora were observed after oral administration of moxifloxacin. The number of E. coli, Bacillus spp., Enterococcus and Klebsiella spp. decreased, as did the anaerobes Bacteroides vulgatus, Bifidobacterium spp., Eubacterium and Peptostreptococcus. The number of Bacteroides fragilis was increased. The number of the above microorganisms returned to normal within 2 weeks.
Resistance
Resistance mechanisms that inactivate penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not affect the antibacterial efficacy of moxifloxacin. Other resistance mechanisms, such as entry barriers (common in Pseudomonas aeruginosa) and efflux mechanisms, may affect susceptibility to moxifloxacin.
The development of resistance to moxifloxacin in vitro has been observed to be a gradual process involving point mutations in both types of topoisomerase II, DNA gyrase and topoisomerase IV. Moxifloxacin is a weak substrate for active efflux mechanisms in Gram-positive microorganisms.
Cross-resistance with other fluoroquinolones has been observed. However, since moxifloxacin inhibits both topoisomerases II and IV with similar activity in some Gram-positive bacteria, these bacteria may be resistant to other quinolones but sensitive to moxifloxacin.
Checkpoints
Clinical MICs and disk diffusion breakpoints for moxifloxacin (01.01.2012) according to EUCAST (European Committee on Antimicrobial Susceptibility Testing)
Table 1.
| Microorganism | Sensitive | Resistant |
| Staphylococcus spp. | ≤ 0.5 mg/l ³ 24 mm | > 1 mg/l 21 mm |
| S. pneumoniae | ≤ 0.5 mg/l ³ 22 mm | > 0.5 mg/l 22 mm |
| Streptococcus, groups A, B, C, G | ≤ 0.5 mg/l ³ 18 mm | > 1 mg/l 15 mm |
| H. influenzae | ≤ 0.5 mg/l ³ 25 mm | > 0.5 mg/l 25 mm |
| M. catarrhalis | ≤ 0.5 mg/l ³ 23 mm | > 0.5 mg/l 23 mm |
| Enterobacteriaceae | ≤ 0.5 mg/l ³ 20 mm | > 1 mg/l 17 mm |
| Control points not related to the view* | ≤ 0.5 mg/l | > 1 mg/l |
* Non-species breakpoints were determined primarily from pharmacokinetic/pharmacodynamic data and are independent of species-specific MIC distributions. These data are used only for species for which no species-specific breakpoints have been provided and are not used for species for which interpretive criteria are to be defined.
Microbiological susceptibility
The frequency of acquired resistance may vary depending on the geographical location of the region and the time period determined for certain species of microorganisms. It is desirable to have access to local information on the resistance of microorganisms, especially when treating severe infections.
If necessary, advice from an expert in antibiotic resistance should be sought when the local prevalence of resistance is so strong that the effectiveness of a particular drug against at least some types of infectious agents remains questionable.
Sensitive species
Gardnerella vaginalis; Staphylococcus aureus* (sensitive to methicillin); Streptococcus agalactiae (group B); Streptococcus milleri group* (S. anginosus, S. constellatus and S. intermedius); Streptococcus pneumoniae*; Streptococcus pyogenes* (group A); Streptococcus viridans group (S. viridans, S. mutans, S. mitis, S. sanguinis, S. salivarius, S. thermophilus).
Aerobic Gram-negative microorganisms
Acinetobacter baumannii; Haemophilus influenzae*; Haemophilus parainfluenzae*; Legionella pneumophila; Moraxella (Branhamella) catarrhalis*
Anaerobic microorganisms
Fusobacterium spp.; Prevotella spp.
Other microorganisms
Chlamydophila (Chlamydia) pneumoniae*; Chlamydia trachomatis*; Coxiella burnetii; Mycoplasma genitalium; Mycoplasma hominis; Mycoplasma pneumoniae*
Species that may acquire resistance
Aerobic Gram-positive microorganisms
Enterococcus faecalis*; Enterococcus faecium*; Staphylococcus aureus (methicillin-resistant)+.
Aerobic Gram-negative microorganisms
Enterobacter cloacae*; Escherichia coli*#; Klebsiella pneumoniae*#; Klebsiella oxytoca; Neisseria gonorrhoeae*+; Proteus mirabilis*.
Anaerobic microorganisms
Bacteroides fragilis*; Peptostreptococcus spp.*
Resistant species
Aerobic Gram-negative microorganisms
Pseudomonas aeruginosa.
* Satisfactory activity against susceptible strains has been demonstrated in clinical studies within the approved clinical indications.
#Strains that produce ESBLs are usually resistant to fluoroquinolones.
+Resistance rate > 50% in one or more countries.
Pharmacokinetics
Absorption and bioavailability
When administered orally, moxifloxacin is rapidly and almost completely absorbed. Absolute bioavailability is approximately 91%.
When single doses of 50–800 mg and daily doses of 600 mg are used for 10 days, the pharmacokinetics are linear. Steady state is reached within 3 days.
After a single dose of 400 mg, the maximum plasma concentration (Cmax) is reached within 0.5–4 hours and is 3.1 mg/l. The maximum and minimum plasma concentrations at steady state (400 mg once daily) are 3.2 and 0.6 mg/l, respectively. At steady state, the exposure within the dosing interval is almost 30% higher than after the first dose.
Distribution
Moxifloxacin is rapidly distributed in the extravascular space, after a dose of 400 mg AUC is 35 μg/l. The volume of distribution at steady state is 2 l/kg. As established in in vitro and ex vivo experiments, binding to blood proteins is approximately 40–42% and does not depend on the concentration of the drug.
Peak concentration (geometric mean) after oral administration of a single dose of moxifloxacin 400 mg.
Table 2.
| Cloth | Concentration | Local level – blood plasma level |
| Plasma | 3.1 mg/l | - |
| Saliva | 3.6 mg/l | 0.75 – 1.3 |
| Blister contents | 1.61 mg/l | 1.71 |
| Mucous membrane of the bronchi | 5.4 mg/kg | 1.7 – 2.1 |
| Alveolar macrophages | 56.7 mg/kg | 18.6 – 70.0 |
| Epithelial layer fluid | 20.7 mg/l | 5 – 7 |
| Hymorov's sinus | 7.5 mg/kg | 2.0 |
| Ethmoid sinuses | 8.2 mg/kg | 2.1 |
| Nasal polyps | 9.1 mg/kg | 2.6 |
| Interstitial fluid | 1.02 mg/l | 0.8 – 1.42.3 |
| Female genitalia* | 10.24 mg/kg | 1,724 |
* Intravenous administration of a single dose of 400 mg.
1 10 hours after administration.
2 Free concentration.
3 From 3 hours to 36 hours after dosing.
4 At the end of the infusion.
Metabolism
Moxifloxacin undergoes phase II biotransformation and is excreted from the body by the kidneys and with feces/bile both in an unchanged form and in the form of inactive metabolites: sulfo compounds (M1) and glucuronides (M2). M1 and M2 are microbiologically inactive. During in vitro studies and phase I clinical studies, no metabolic pharmacokinetic interaction with other drugs involved in phase I biotransformation with the participation of cytochrome P450 enzymes was observed. There are no signs of oxidative metabolism.
Excretion from the body
The elimination half-life of the drug is approximately 12 hours. The mean total clearance after administration of 400 mg is from 179 to 246 ml/min. Renal clearance is approximately 24–53 ml/min and indicates partial tubular reabsorption of the drug from the kidneys. After a dose of 400 mg, urinary excretion (about 19% - unchanged drug, about 2.5% - M1 and about 14% - M2) and feces (about 25% - unchanged drug, about 36% - M1 and no excretion as M2) was approximately 96%. Concomitant use of ranitidine and probenecid does not change the renal clearance of the drug.
Pharmacokinetics in different patient groups.
Elderly patients and patients with low body weight
Higher plasma concentrations of the drug were observed in healthy volunteers with low body weight (in particular, women) and in healthy elderly volunteers.
Kidney failure.
No significant changes in the pharmacokinetics of moxifloxacin were observed in patients with impaired renal function (including patients with creatinine clearance > 20 ml/min/1.73 m2). As renal function decreases, the concentration of the metabolite M2 (glucuronide) increases to 2.5 (in patients with creatinine clearance 2).
Based on pharmacokinetic data in patients with hepatic impairment (Child-Pugh class A-C), it is not possible to determine whether there is a difference compared to healthy volunteers. Impaired liver function was associated with higher plasma exposure to M1, while the exposure to the parent drug was comparable to that in healthy volunteers. There is insufficient clinical experience with moxifloxacin in patients with hepatic impairment.
Indication
Treatment of the following bacterial infections caused by susceptible microorganisms (see sections "Pharmacological properties", "Features of use", "Adverse reactions") in patients aged 18 years and older. Moxifloxacin should be prescribed only when the use of antibacterial agents that are usually recommended for the initial treatment of the following infections is inappropriate or when the indicated treatment has been ineffective.
Acute bacterial sinusitis (diagnosed with a high degree of probability). Exacerbation of chronic obstructive pulmonary disease, including bronchitis (diagnosed with a high degree of probability). Community-acquired pneumonia, except for severe community-acquired pneumonia.
Mild to moderate pelvic inflammatory disease (including upper genital tract infections in women, including salpingitis and endometritis), not associated with tubo-ovarian abscess or pelvic abscesses. Moxifloxacin tablets are not recommended for use as monotherapy in mild to moderate pelvic inflammatory disease, but may be used in combination with other appropriate antibacterial agents (e.g. cephalosporins) due to the increasing resistance of Neisseria gonorrhoeae to moxifloxacin (except for moxifloxacin-resistant strains of N. gonorrhoeae) (see sections 5.1 and 5.2).
Moxifloxacin tablets can be used to complete a course of treatment in which initial therapy with parenteral moxifloxacin has been effective and is indicated for the following indications: community-acquired pneumonia; complicated skin and subcutaneous tissue infections. Moxifloxacin tablets are not recommended for initial treatment of any skin and subcutaneous tissue infections or in severe community-acquired pneumonia. Official guidance on the appropriate use of antibacterial agents should be consulted.
Contraindication
Known hypersensitivity to moxifloxacin or to other quinolones or to any of the excipients of the drug. Age up to 18 years. Pregnancy or breastfeeding (see section "Use during pregnancy or breastfeeding"). History of tendon diseases associated with quinolone treatment. In preclinical and clinical studies, changes in cardiac electrophysiology in the form of QT interval prolongation were observed after the use of moxifloxacin. Therefore, for safety reasons, the drug is contraindicated in patients with: congenital or diagnosed acquired QT interval prolongation; electrolyte imbalance, in particular with uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; symptomatic arrhythmias in history.
The drug should not be used concomitantly with other drugs that prolong the QT interval (see section "Interaction with other medicinal products and other types of interactions").
Due to limited clinical data, the use of the drug is also contraindicated in patients with impaired liver function (Child-Pugh class C) and in patients with elevated transaminase levels (5 times the upper limit of normal).
Interaction with other medicinal products and other types of interactions
An additive effect of moxifloxacin and other medicinal products that may prolong the QT interval cannot be excluded. This interaction increases the risk of ventricular arrhythmias, including torsade de pointes. For this reason, the use of moxifloxacin in combination with any of the following medicinal products is contraindicated (see also section "Contraindications"):
Class IA antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide); Class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide); Antipsychotics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride); Tricyclic antidepressants; Some antimicrobials (saquinavir, sparfloxacin, intravenous erythromycin, pentamidine, antimalarials, including halofantrine); Some antihistamines (terfenadine, astemizole, mizolastine); Others (cisapride, vincamine IV, bepridil, diphemanil).
An interval of about 6 hours is required between taking drugs containing divalent or trivalent cations (such as antacids containing magnesium or aluminum, didanosine tablets, sucralfate, and drugs containing iron or zinc) and moxifloxacin.
When activated charcoal is administered simultaneously with oral moxifloxacin at a dose of 400 mg, the systemic bioavailability of the drug is reduced by more than 80% due to inhibition of its absorption. Therefore, the simultaneous use of these two drugs is not recommended (except in cases of overdose, see also the section "Overdose").
After multiple doses of moxifloxacin in healthy volunteers, an increase in Cmax of digoxin by approximately 30% at steady state was observed, without any effect on AUC (area under the concentration-time curve) or to lower levels. Therefore, there is no need for precautions when taking digoxin concomitantly.
In studies in diabetic volunteers, concomitant oral administration of moxifloxacin and glibenclamide resulted in a decrease in peak glibenclamide concentrations of approximately 21%. The combination of glibenclamide with moxifloxacin could theoretically lead to a slight transient hyperglycemia. However, the observed changes in pharmacokinetics did not result in changes in pharmacodynamic parameters (blood glucose levels, insulin levels). Thus, no clinically relevant interaction between moxifloxacin and glibenclamide was observed.
Change in the value of the international normalized ratio (INR)
There have been numerous reports of increased anticoagulant activity in patients receiving oral anticoagulants in combination with antibacterial agents, including fluoroquinolones, macrolides, tetracyclines, cotrimoxazole and some cephalosporins. Risk factors include infectious diseases (and concomitant inflammation), age and general condition of the patient. In these circumstances, it is difficult to assess whether the infection or the treatment is causing the deviation in the international normalized ratio (INR). As a precautionary measure, more frequent monitoring of the INR may be considered. If necessary, appropriate adjustment of the oral anticoagulant dose should be made.
Substances for which no clinically significant interaction with moxifloxacin has been demonstrated: ranitidine, calcium supplements, theophylline, oral contraceptives, cyclosporine, itraconazole, parenteral morphine, probenecid. In vitro studies of cytochrome P450 enzymes in humans have confirmed the above. In view of the above results, metabolic interaction via cytochrome P450 enzymes is unlikely.
The absorption of moxifloxacin is not affected by food intake (including dairy products). Therefore, moxifloxacin can be taken regardless of meals.
Application features
Moxifloxacin should be avoided in patients who have had a serious adverse reaction to a quinolone or fluoroquinolone-containing drug in the past (see section 4.8). Treatment of these patients with moxifloxacin should only be initiated if no alternative treatment options are available and after a careful benefit/risk assessment (see section 4.8).
The benefits of treatment with moxifloxacin, especially in the case of non-serious infections, should be assessed taking into account the information contained in this section.
Prolonged, disabling and potentially irreversible serious adverse reactions
Very rare cases of prolonged (months or years) disabling and potentially irreversible serious adverse reactions affecting various, sometimes multiple, body systems (musculoskeletal, nervous, mental and sensory) and existing risk factors have been reported in patients treated with quinolones and fluoroquinolones, regardless of age. Moxifloxacin treatment should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to seek medical advice.
QTc interval prolongation and clinical conditions in which QTc interval prolongation is possible
Moxifloxacin has been associated with an increase in the QT interval on the electrocardiogram in some patients. Analysis of ECG data showed that the QTc interval increased by 6 ms ± 26 ms (1.4% from baseline) with moxifloxacin. Since women have a longer QT interval than men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients may also be more susceptible to drug-related QT effects.
Patients taking moxifloxacin should be cautious when using drugs that may lead to a decrease in potassium levels (see sections “Contraindications”, “Interaction with other medicinal products and other types of interactions”).
If symptoms of arrhythmia occur during treatment with the drug, treatment should be discontinued and an ECG should be performed.
Hypersensitivity/allergic reactions
Cases of hypersensitivity and allergic reactions have been reported after the first use of fluoroquinolones, including moxifloxacin. Anaphylactic reactions can take the form of life-threatening anaphylactic shock, even after the first use of the drug. In cases of clinical manifestation of severe hypersensitivity reactions, moxifloxacin should be discontinued and appropriate therapy (e.g. antishock) should be initiated.
Severe liver dysfunction
Cases of fulminant hepatitis, potentially leading to hepatic failure (including fatal outcomes), have been reported with moxifloxacin (see section 4.8). If symptoms of fulminant hepatitis occur, such as rapidly progressive asthenia accompanied by jaundice, dark urine, bleeding tendency or hepatic encephalopathy, patients are advised to consult their doctor before continuing treatment.
If symptoms of liver dysfunction occur, liver function tests/examination should be performed.
Severe bullous skin reactions
Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (TEN: also known as Lyell's syndrome), Stevens-Johnson syndrome (SJS) and acute generalised exanthematous pustulosis (AGEP) have been reported, which can be life-threatening or fatal (see section 4.8). When prescribing moxifloxacin, patients should be informed of the signs and symptoms of severe cutaneous reactions and monitored closely. If appropriate signs and symptoms occur, moxifloxacin should be discontinued immediately and alternative treatment should be considered. If a patient develops serious reactions such as SJS, TEN or AGEP while taking moxifloxacin, moxifloxacin should be discontinued.
Patients prone to seizures
Quinolones are known to induce seizures. Moxifloxacin should be used with caution in patients with central nervous system (CNS) disorders or other risk factors that may predispose to seizures or lower the seizure threshold. If seizures occur, moxifloxacin should be discontinued and appropriate measures taken.
Peripheral neuropathy
Cases of sensory or sensorimotor polyneuropathy, resulting in paresthesia, hypoesthesia, dysesthesia or weakness, have been reported in patients taking quinolones, including moxifloxacin. Patients taking moxifloxacin are advised to inform their doctor of the development of symptoms of neuropathy such as pain, burning, tingling, numbness or weakness before continuing treatment, to prevent the development of irreversible conditions (see section "Adverse reactions").
Mental reactions
Psychiatric reactions may occur even after the first use of quinolones, including moxifloxacin. In rare cases, depression or psychotic reactions have led to suicidal thoughts and self-harm, including suicide attempts (see section "Adverse reactions"). If a patient develops such reactions, moxifloxacin should be discontinued and appropriate measures taken. It is recommended that moxifloxacin be prescribed with caution to patients suffering from psychosis and patients with a history of psychiatric illness.
Antibiotic-associated diarrhea, including colitis
Antibiotic-associated diarrhea (AAD) and antibiotic-associated colitis (AAC), including pseudomembranous colitis and Clostridium difficile-associated diarrhea, have been reported with the use of broad-spectrum antibiotics, including moxifloxacin, and range in severity from mild diarrhea to fatal colitis. Therefore, it is important to consider the possibility of such a diagnosis in patients who develop severe diarrhea during or after the use of moxifloxacin. If AAD or AAC is suspected or confirmed, treatment with antimicrobials, including moxifloxacin, should be discontinued and appropriate therapeutic measures should be initiated immediately. In addition, appropriate sanitary and epidemiological measures should be taken to reduce the risk of transmission of infection. Drugs that inhibit peristalsis are contraindicated in patients with severe diarrhea.
Patients with myasthenia gravis
Moxifloxacin should be used with caution in patients with myasthenia gravis due to the possibility of exacerbation of symptoms.
Tendonitis and tendon rupture (especially but not limited to the Achilles tendon), sometimes bilateral, may occur as early as 48 hours after initiation of treatment with quinolones and fluoroquinolones, including moxifloxacin, even within 48 hours of initiation of treatment and have been reported to occur up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal impairment, patients with solid organ transplantation and those receiving concomitant corticosteroids. Therefore, concomitant use of corticosteroids should be avoided. At the first signs of tendinitis (e.g. painful swelling, inflammation), moxifloxacin should be discontinued and alternative treatment considered. The affected limb(s) should be treated appropriately (e.g. immobilization). Corticosteroids should not be used if symptoms of tendinopathy occur.
Patients with renal impairment
Moxifloxacin should be used with caution in elderly patients with renal impairment if they are unable to maintain adequate fluid intake, as dehydration increases the risk of renal failure.
Visual impairment
If visual impairment or other effects on the organs of vision are observed, you should immediately consult an ophthalmologist (see sections “Ability to influence the speed of reactions when driving vehicles or other mechanisms”, “Adverse reactions”).
Dysglycemia
As with all fluoroquinolones, blood glucose abnormalities, including hypoglycemia and hyperglycemia, have been reported with moxifloxacin. Among patients treated with moxifloxacin, dysglycemia has occurred predominantly in elderly patients with diabetes mellitus receiving concomitant oral hypoglycemic agents (e.g. sulfonylureas) or insulin. Close monitoring of blood glucose levels is recommended in diabetic patients (see section 4.8). Hypoglycemic coma has been reported.
Prevention of photosensitivity reactions
Photosensitivity reactions have been reported in patients treated with quinolones. However, studies have shown that moxifloxacin has a lower risk of photosensitivity. Despite this, patients should be advised to avoid both ultraviolet radiation and prolonged and/or intense sunlight during treatment with moxifloxacin.
Patients suffering from glucose-6-phosphate dehydrogenase deficiency
Patients with a family or personal history of glucose-6-phosphate dehydrogenase deficiency are more likely to develop hemolytic reactions when treated with quinolones. Therefore, moxifloxacin should be used with caution in such patients.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Patients with pelvic inflammatory disease
In patients with complicated pelvic inflammatory disease (e.g. associated with tubo-ovarian abscess or pelvic abscess) for whom intravenous therapy is considered necessary, treatment with moxifloxacin 400 mg film-coated tablets is not recommended.
Pelvic inflammatory disease may be caused by Neisseria gonorrhoeae resistant to fluoroquinolones. Therefore, in such cases, empirical use of moxifloxacin should be combined with another appropriate antibiotic (e.g. cephalosporin) unless the presence of Neisseria gonorrhoeae resistant to moxifloxacin cannot be completely excluded. If clinical improvement does not occur after 3 days of treatment, therapy should be reviewed.
Patients with specific complicated skin and subcutaneous tissue infections
The clinical efficacy of intravenous moxifloxacin in the treatment of severe infections associated with burns, fasciitis, and diabetic foot accompanied by osteomyelitis has not been established.
Impact on biological tests
Treatment with moxifloxacin may interfere with culture tests for Mycobacterium spp. due to inhibition of microbial growth, which may lead to false-negative results.
Patients with infections caused by methicillin-resistant Staphylococcus aureus (MRSA)
Moxifloxacin is not recommended for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In case of suspected or confirmed MRSA infection, treatment with an appropriate antibacterial agent should be initiated (see section 5.1).
Epidemiological studies have reported an increased risk of aortic aneurysm and dissection, especially in elderly patients, and of aortic and mitral valve regurgitation after the use of fluoroquinolones. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and of regurgitation/insufficiency of any of the cardiac valves have been reported in patients receiving fluoroquinolones (see section 4.8).
Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with a positive family history of aneurysm or congenital heart valve disease, or in patients with an existing diagnosis of aortic aneurysm and/or dissection, or heart valve disease, or in the presence of other risk factors or predisposing conditions.
· both for aortic aneurysm and dissection, and for regurgitation/valve insufficiency (e.g. connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis) or additionally
· in case of aortic aneurysm and dissection (e.g. vascular disorders such as Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren's syndrome) or additionally
· with regurgitation/valvular insufficiency (e.g. infective endocarditis). The risk of aortic aneurysm and dissection and their rupture may be increased in patients receiving concomitant systemic corticosteroids.
Patients should seek immediate medical attention in the emergency department if they experience sudden abdominal, chest, or back pain.
Patients should be advised to seek immediate medical attention in the event of acute shortness of breath, new onset of palpitations, or development of abdominal or lower extremity edema.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies on the effects of moxifloxacin on the ability to drive and use machines have been conducted. However, fluoroquinolones, including moxifloxacin, may impair the ability to drive or use machines due to central nervous system reactions (e.g. dizziness, acute transient loss of vision or acute transient loss of consciousness, fainting (see section 4.8). Patients should be advised to observe their reaction to moxifloxacin before driving or using machines.
Use during pregnancy or breastfeeding
Pregnancy
The safety of moxifloxacin during pregnancy has not been established. Animal studies have shown reproductive toxicity. The potential risk to humans has not been established.
Due to the risk of damage to the supporting joints of young animals by fluoroquinolones (according to experimental data) and the reversible joint lesions described in children treated with some fluoroquinolones, moxifloxacin should not be administered to pregnant women (see section "Contraindications").
Breast-feeding
Moxifloxacin, like other quinolones, has been shown to cause damage to the articular cartilage of young animals. Preclinical studies have shown that small amounts of moxifloxacin may pass into breast milk. There are no data on the use of the drug in breastfeeding women. Therefore, the use of moxifloxacin is contraindicated during breastfeeding (see section "Contraindications").
Fertility
Animal studies have not shown any effect on fertility.
Method of administration and doses
Adults
It is recommended to take 1 tablet (400 mg) of moxifloxacin per day.
The tablets should be taken without chewing, with sufficient water. The drug can be taken regardless of the time of eating.
Duration of therapy
The duration of therapy with Moxifloxacin in tablet form depends on the type of infection and is:
- exacerbation of chronic obstructive pulmonary disease, including bronchitis - 5–10 days;
- community-acquired pneumonia – 10 days;
- acute bacterial sinusitis – 7 days;
- inflammatory diseases of the pelvic organs of mild and moderate severity
