Instructions Avelox solution for infusion 400 mg bottle 250 ml No. 1
Composition
active ingredient: moxifloxacin;
1 bottle (250 ml of solution) contains 436 mg of moxifloxacin hydrochloride, corresponding to 400 mg of moxifloxacin;
Excipients: sodium chloride, diluted hydrochloric acid, sodium hydroxide, water for injections.
Dosage form
Solution for infusion.
Main physicochemical properties: clear yellow solution.
Pharmacotherapeutic group
Antimicrobial drugs for systemic use. Antibacterial agents of the quinolone group. ATX code J01M A14.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Moxifloxacin inhibits bacterial type II topoisomerases (DNA gyrase and topoisomerase IV), which are essential for the replication, transcription and repair of bacterial DNA.
Pharmacokinetics/pharmacodynamics
The ability of fluoroquinolones to kill bacteria is directly dependent on their concentration. Pharmacodynamic studies of fluoroquinolones in animal models of infectious and inflammatory diseases and in humans indicate that the main determinant of efficacy is the ratio between the area under the pharmacokinetic curve (AUC24) and the minimum inhibitory concentration (MIC).
Mechanism of resistance
Resistance to fluoroquinolones can arise from mutations in DNA gyrase and topoisomerase IV. Other mechanisms include overexpression of efflux pumps, impermeability, and protein-mediated protection of DNA gyrase. Cross-resistance can be expected between moxifloxacin and other fluoroquinolones.
Resistance mechanisms common to antibacterial agents belonging to other classes do not affect the antibacterial efficacy of moxifloxacin.
Limit values
Clinical MICs and disk diffusion test breakpoints of moxifloxacin according to EUCAST (European Committee on Antimicrobial Susceptibility Testing) (01.01.2012):
| Microorganism | Sensitive | Resistant |
| Staphylococcus spp. | ≤ 0.5 mg/l ≥ 24 mm | > 1 mg/l < 21 mm |
| S. pneumoniae | ≤ 0.5 mg/l ≥ 24 mm | > 0.5 mg/l < 22 mm |
| Streptococcus groups A, B, C, G | ≤ 0.5 mg/l ≥ 18 mm | > 1 mg/l < 15 mm |
| H. influenzae | ≤ 0.5 mg/l ≥ 25 mm | > 0.5 mg/l < 25 mm |
| M. catarrhalis | ≤ 0.5 mg/l ≥ 23 mm | > 0.5 mg/l < 23 mm |
| Enterobacteriaceae | ≤ 0.5 mg/l ≥ 20 mm | > 1 mg/l < 17 mm |
| Limit values not related to the bacterial species* | ≤ 0.5 mg/l | > 1 mg/l |
* Non-species-specific breakpoints were determined primarily based on the relationship between pharmacokinetic and pharmacodynamic data and are independent of species-specific MICs. These data are used for species that do not have individually defined breakpoints and are not applicable to species where interpretative criteria are to be defined.
Microbiological susceptibility
The prevalence of acquired resistance of isolated species may vary with location and time, and local information on resistance is therefore necessary, particularly in the treatment of severe infections. Specialist advice should be sought when the local prevalence of resistance is such that the benefit of the agent, at least in some types of infections, is questionable.
Typically sensitive species of microorganisms
Aerobic Gram-positive microorganisms
Staphylococcus aureus*+
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 baumanii
Haemophilus influenzae*
Legionella pneumophila
Moraxella (Branhamella) catarrhalis*
Anaerobic microorganisms
Prevotella spp.
Other microorganisms
Chlamydophila (Chlamydia) pneumoniae*
Coxiella burnetii
Mycoplasma pneumoniae*
Species for which resistance may develop
Aerobic Gram-positive microorganisms
Enterococcus faecalis*
Enterococcus faecium*
Aerobic Gram-negative microorganisms
Enterobacter cloacae*
Escherichia coli*#
Klebsiella pneumoniae*#
Klebsiella oxytoca
Proteus mirabilis*
Anaerobic microorganisms
Bacteroides fragilis*
Resistant microorganisms
Aerobic Gram-negative microorganisms
Pseudomonas aeruginosa
* Efficacy has been sufficiently demonstrated in clinical studies.
+ Methicillin-resistant S. aureus is very often also resistant to fluoroquinolones. In methicillin-resistant S. aureus, the resistance rate to moxifloxacin is more than 50%.
# Strains that produce extended-spectrum beta-lactamase (ESBL) are also resistant to fluoroquinolones.
Pharmacokinetics
After a single infusion of 400 mg of the drug over 1 hour, the maximum concentration of the drug is reached at the end of the infusion and is approximately 4.1 mg/l, which is approximately 26% higher than when the drug is administered orally (3.1 mg/l). The AUC is approximately 39 mg*h/l after intravenous administration, which is only slightly higher than when the drug is administered orally (35 mg*h/l); the absolute bioavailability is approximately 91%. When moxifloxacin is administered intravenously, there is no need to adjust the dose according to the age or gender of the patients. The pharmacokinetics are linear in the range of 50–200 mg for a single oral dose, up to 600 mg for a single intravenous dose and up to 600 mg for once-daily administration for 10 days.
Distribution
Moxifloxacin is rapidly distributed in the extravascular space. The volume of distribution at steady state (Vss) is approximately 2 l/kg. In vitro and ex vivo studies have shown that protein binding is approximately 40–42%, independent of drug concentration. Moxifloxacin is mainly bound to serum albumin.
Peak concentrations of 5.4 mg/kg and 20.7 mg/l (geometric mean) were observed in bronchial mucosa and epithelial lining fluid, respectively, 2.2 hours after oral dosing. The corresponding peak concentration in alveolar macrophages was 56.7 mg/kg. In cutaneous vesicle fluid, a concentration of 1.75 mg/l was observed 10 hours after intravenous administration. The free concentration-time profile for interstitial fluid is similar to that for plasma, with a peak free concentration of 1.0 mg/l (geometric mean) occurring approximately 1.8 hours after intravenous administration.
Metabolism
Moxifloxacin undergoes phase II biotransformation and is excreted from the body by the kidneys (about 40%) and with feces/bile (about 60%) both in an unchanged form and in the form of sulfoconjugates (M1) and glucuronides (M2). M1 and M2 are metabolites relevant only for humans, both of which are microbiologically inactive.
In in vitro and phase I clinical studies, no metabolic pharmacokinetic interactions with other drugs involved in phase I biotransformation, including cytochrome P450 enzymes, were observed. There is no evidence of oxidative metabolism.
Breeding
The plasma half-life of moxifloxacin is approximately 12 hours. The mean estimated total clearance after administration of 400 mg is 179 to 246 ml/min. After intravenous administration of 400 mg, urinary excretion of unchanged drug was approximately 22% and faecal excretion was 26%. Total excretion of the dose (unchanged drug and metabolites) was approximately 98% after intravenous administration of the drug. Renal clearance is approximately 24–53 ml/min, indicating partial tubular reabsorption of the drug by the kidneys. Concomitant administration of ranitidine and probenecid with moxifloxacin does not alter the renal clearance of the parent drug.
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). With a decrease in renal function, the concentration of metabolite M2 (glucuronide) increases by almost 2.5 times (with creatinine clearance < 30 ml/min/1.73 m2).
Liver dysfunction
Pharmacokinetic data in patients with hepatic impairment (Child-Pugh class A, B) do not allow definitive determination of whether there are any differences in the parameters of patients with impaired hepatic function and healthy volunteers. Impaired hepatic function was associated with higher plasma exposure to M1, while exposure to the parent drug was similar to that in healthy volunteers. There is insufficient clinical experience with moxifloxacin in patients with hepatic impairment.
Preclinical safety data
In conventional studies of repeated doses of moxifloxacin, hematological toxicity and hepatotoxicity were observed in animals. Central nervous system (CNS) toxicity was observed. These effects were observed after administration of high doses of moxifloxacin or after prolonged use.
High oral doses in animals (≥ 60 mg/kg), with plasma concentrations ≥ 20 mg/l, caused changes in electroretinogram parameters and, in some cases, retinal atrophy.
Following intravenous administration, systemic toxicity was most pronounced when moxifloxacin was administered by bolus injection (45 mg/kg) and was not observed when moxifloxacin (40 mg/kg) was administered by slow infusion over 50 minutes.
After intraarterial administration, inflammatory changes were observed with spread to periarterial soft tissues, indicating that intraarterial administration of moxifloxacin should be avoided.
In vitro, moxifloxacin at high concentrations affected electrophysiological parameters of cardiac activity, which could cause prolongation of the QT interval.
After intravenous administration of moxifloxacin to animals at a dose of 30 mg/kg by infusions lasting 15, 30 or 60 minutes, the degree of prolongation of the QT interval was observed to depend on the infusion rate: the shorter the infusion time, the more pronounced the prolongation of the QT interval. No prolongation of the QT interval was observed when a dose of 30 mg/kg was administered by infusion lasting 60 minutes.
In animal reproductive studies, moxifloxacin has been shown to cross the placenta. Animal studies have not revealed any teratogenic effects of moxifloxacin or impairment of fertility after its use. In animals, a slight increase in the incidence of malformations of the spine and ribs was observed, but only at a dose (20 mg/kg intravenously) associated with severe maternal toxicity. An increase in the incidence of abortions in animals was observed at therapeutic plasma concentrations expected in humans.
Quinolones, including moxifloxacin, are known to cause damage to the cartilage of large diarthrodial joints in immature animals.
Indication
Community-acquired pneumonia.
Complicated infectious diseases of the skin and subcutaneous tissues.
Moxifloxacin should only be used when other antibacterial agents that are usually recommended for the initial treatment of these infections are inappropriate.
Attention should be paid to official instructions on the proper use of antibacterial agents.
Contraindication
Hypersensitivity to moxifloxacin, other quinolone antibiotics or any of the excipients; pregnancy or breastfeeding (see section "Use during pregnancy or breastfeeding"); childhood (up to 18 years); history of tendon disease/pathology associated with the use of quinolones.
During preclinical and clinical studies, changes in electrophysiological parameters of cardiac activity, manifested by prolongation of the QT interval, were observed after administration of moxifloxacin. For this reason, moxifloxacin is contraindicated in patients with:
Congenital or acquired QT prolongation; Electrolyte imbalance, especially in the case of uncorrected hypokalemia; Clinically significant bradycardia; Clinically significant heart failure with reduced left ventricular ejection fraction; History of symptomatic arrhythmias.
Moxifloxacin should not be used concomitantly with drugs that prolong the QT interval (see also section “Interaction with other medicinal products and other types of interactions”).
Due to insufficient clinical experience, moxifloxacin is contraindicated in patients with impaired liver function (Child-Pugh class C) and increased transaminase levels by five times or more.
Special safety measures.
One vial of the drug is intended for single use only. Unused solution should be disposed of.
The following solutions have been found to be compatible with moxifloxacin 400 mg solution for infusion: water for injections; 0.9% sodium chloride solution; 1 molar sodium chloride solution; 5%, 10%, 40% glucose solution; 20% xylitol solution; Ringer's solution; complex sodium lactate solutions (Hartmann's solution, lactated Ringer's solution).
Moxifloxacin infusion solution should not be administered concomitantly with other drugs.
Do not use the drug if there are visible solid impurities or if the solution is cloudy.
When stored in a cool place, a precipitate may form, which dissolves at room temperature. Therefore, it is not recommended to store the infusion solution at a temperature below 15 °C.
Interaction with other medicinal products and other types of interactions
Drug interactions
An additive effect of moxifloxacin and other medicinal products that can cause QTc prolongation cannot be excluded. This effect may lead to the development of ventricular arrhythmias, including polymorphic ventricular tachycardia of the pirouette type. 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, erythromycin IV, pentamidine, antimalarials, including halofantrine); Some antihistamines (terfenadine, astemizole, mizolastine); Other drugs (cisapride, vincamine IV, bepridil, diphemanil).
After multiple administration of moxifloxacin in healthy volunteers, an increase in Cmax of digoxin by approximately 30% was observed without any effect on AUC or the level of the curve.
In studies involving volunteers with diabetes, simultaneous use of oral moxifloxacin and glibenclamide resulted in a decrease in the maximum concentration of glibenclamide in the blood plasma by approximately 21%. The combination of glibenclamide with moxifloxacin can theoretically provoke the development of a slight short-term hyperglycemia. However, the observed changes in the pharmacokinetics of glibenclamide did not cause changes in the pharmacodynamic parameters (blood glucose level, insulin level). Therefore, there is no clinically significant interaction between moxifloxacin and glibenclamide.
Change in the value of the international normalized ratio (INR).
There have been numerous reports of increased activity of oral anticoagulants in patients receiving antimicrobials, particularly fluoroquinolones, macrolides, tetracyclines, cotrimoxazole and some cephalosporins. Risk factors include infectious and inflammatory diseases, age and general condition of the patient. Therefore, it is difficult to determine whether the INR changes are caused by the infection or the treatment. As a precautionary measure, the INR can be checked more frequently. If necessary, the dose of the oral anticoagulant should be adjusted appropriately.
In clinical studies, the following substances have been shown to have no clinically significant interactions with moxifloxacin: ranitidine, probenecid, oral contraceptives, calcium supplements, parenteral morphine, theophylline, cyclosporine or itraconazole.
In vitro studies using human cytochrome P450 enzymes confirmed these results. Thus, metabolic interactions via cytochrome P450 enzymes are unlikely.
Interaction with food
Moxifloxacin does not show clinically significant interactions with food, including dairy products.
Application features
Moxifloxacin should be avoided in patients with a history of serious adverse reactions to quinolone or fluoroquinolone-containing medicinal products (see section 4.8). Treatment of such patients with moxifloxacin should only be initiated in the absence of alternative therapy and after a careful benefit/risk assessment (see also 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.
QTc prolongation and clinical conditions in which QTc prolongation is possible
Moxifloxacin has been shown to prolong the QTc interval on the electrocardiogram in some patients. The extent of QT prolongation may increase with increasing plasma concentrations of the drug during rapid intravenous infusion. Therefore, the recommended infusion duration should be at least 60 minutes and the intravenous dose should not exceed 400 mg once daily. For more information, see sections “Contraindications” and “Interaction with other medicinal products and other forms of interaction”.
Moxifloxacin therapy should be discontinued if symptoms that may be associated with cardiac arrhythmia appear, regardless of whether this is confirmed by ECG results.
Moxifloxacin should be used with caution in patients with conditions predisposing to arrhythmias (e.g. acute myocardial ischemia) as these patients are at increased risk of ventricular arrhythmias (including torsades de pointes) and cardiac arrest (see also sections 4.3 and 4.5). Moxifloxacin should be used with caution in patients taking medicinal products that may lower potassium levels (see also sections 4.3 and 4.5).
Moxifloxacin should be administered with caution to patients receiving medicinal products associated with clinically significant bradycardia (see also section "Contraindications").
Women and elderly patients may be more sensitive to the effects of drugs that cause QTc prolongation, such as moxifloxacin, and therefore such patients require special attention.
Hypersensitivity/allergic reactions
Cases of hypersensitivity and allergic reactions have been reported after the first use of fluoroquinolones, including moxifloxacin. Anaphylactic reactions can develop into life-threatening shock even after the first use of the drug. In the event of clinical manifestations of severe hypersensitivity reactions, moxifloxacin should be discontinued and appropriate treatment (e.g. shock therapy) should be initiated.
Severe liver dysfunction
If signs of liver dysfunction appear, liver function tests should be performed.
Severe skin reactions
Cases of severe skin reactions, including toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, Stevens-Johnson syndrome (SJS) and acute generalised exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported with moxifloxacin (see section 4.8). Patients should be warned about the signs and symptoms of severe skin reactions and monitored closely when prescribing the medicinal product. If signs and symptoms suggestive of such reactions appear, moxifloxacin should be discontinued immediately and alternative treatment should be considered. If a patient develops severe skin reactions such as TENS, TEN or AGEP during moxifloxacin therapy, moxifloxacin should not be restarted in this patient under any circumstances.
Patients prone to seizures
Quinolones are known to cause convulsions. They should be used with caution in patients with CNS disorders or other risk factors that may predispose to convulsions or lower the convulsive threshold. If convulsions occur, moxifloxacin should be discontinued and appropriate measures taken.
Prolonged, disabling and potentially irreversible serious adverse reactions
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) have been reported in patients treated with quinolones and fluoroquinolones, regardless of the patient's age and existing risk factors. Moxifloxacin should be discontinued immediately at the first symptoms of any serious adverse reaction and patients should be advised to seek medical advice.
Peripheral neuropathy
Cases of sensory or sensorimotor polyneuropathy resulting in paresthesia, hypoesthesia, dysesthesia or weakness have been reported in patients treated with quinolones and fluoroquinolones. Patients taking moxifloxacin are advised to inform their doctor if they develop symptoms of neuropathy such as pain, burning, tingling, numbness or weakness before continuing treatment, in order to prevent the development of potentially irreversible conditions (see section "Adverse reactions").
Mental reactions
Psychiatric reactions may occur even after the first use of fluoroquinolones, including moxifloxacin. In rare cases, depression or psychiatric reactions have progressed to the development of suicidal thoughts and self-harm such as suicide attempts (see section "Adverse reactions"). If a patient develops such reactions, treatment with moxifloxacin should be discontinued and appropriate measures should be taken. Caution should be exercised when prescribing moxifloxacin to patients with a history of or current psychiatric disorders.
Antibiotic-associated diarrhea, including colitis
Cases of antibiotic-associated diarrhea (AAD) and antibiotic-associated colitis (AAC), including pseudomembranous colitis and Clostridium difficile-associated diarrhea, have been reported in association with the use of broad-spectrum antibiotics, including moxifloxacin. The severity of these events can range 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 infection control measures should be taken to reduce the risk of transmission. In patients who develop severe diarrhea, agents that inhibit peristalsis are contraindicated.
Patients with myasthenia gravis
Moxifloxacin should be used with caution in patients with myasthenia gravis, as its symptoms may be exacerbated.
Tendonitis and tendon rupture
Tendonitis and tendon rupture (especially, but not limited to, the Achilles tendon), sometimes bilateral, may occur during treatment with quinolones and fluoroquinolones, developing as early as 48 hours after initiation of treatment and may persist for several months after discontinuation of treatment (see sections 4.3 and 4.8). The risk of tendinitis and tendon rupture is increased in the elderly, in patients with renal insufficiency, in patients with solid organ transplants and in patients receiving concomitant corticosteroid therapy. Therefore, concomitant use with corticosteroids should be avoided.
At the first signs of tendinitis (e.g. painful swelling or inflammation), moxifloxacin should be discontinued and alternative therapy considered. Appropriate treatment (e.g. immobilization) should be initiated for the affected limb(s). Corticosteroids should not be used if symptoms of tendinopathy develop.
Epidemiological studies suggest an increased risk of aortic aneurysm and aortic wall dissection, particularly in the elderly, and of aortic and mitral valve regurgitation following the use of fluoroquinolones. Rare cases of aortic aneurysm and aortic wall dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.8). Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and consideration of other therapeutic options in patients with a history of aneurysm or congenital heart valve disease or in patients with a known aortic aneurysm and/or aortic wall dissection or valvular disease, and in the presence of other risk factors or conditions predisposing to the development of both aortic aneurysm and aortic wall dissection and valvular regurgitation/insufficiency (e.g. connective tissue disorders such as Marfan syndrome or vascular Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis) or aortic aneurysm and dissection (e.g. vascular disorders such as Takayasu arteritis or giant cell arteritis, or known atherosclerosis or Sjögren's syndrome) or valvular regurgitation/insufficiency (e.g. infectious endocarditis).
The risk of aortic aneurysm and dissection and rupture may be increased in patients receiving concomitant systemic corticosteroid therapy.
In case of sudden abdominal pain, chest pain or back pain, patients should immediately seek emergency medical attention.
Patients should be advised to seek immediate medical attention if they experience acute shortness of breath, rapid heartbeat, or develop swelling of the abdomen or lower extremities.
Patients with renal impairment
Elderly patients with renal impairment should be given moxifloxacin with caution if they are unable to maintain adequate fluid intake, as dehydration increases the risk of renal failure.
Visual impairment
In case of impaired vision or any effect on the organs of vision, you should immediately seek advice from an ophthalmologist (see sections “Ability to influence the speed of reactions when driving vehicles or working with other mechanisms”, “Adverse reactions”).
Dysglycemia
As with all fluoroquinolones, cases of blood glucose abnormalities, both hypoglycemia and hyperglycemia, have been reported during treatment with moxifloxacin (see section 4.8). Dysglycemia has occurred predominantly in elderly diabetic patients receiving oral hypoglycemic agents (e.g. sulfonylureas) or insulin concomitantly with moxifloxacin. Cases of hypoglycemic coma have been reported. Diabetic patients are advised to closely monitor their blood glucose levels.
Prevention of photosensitivity reactions
Photosensitivity reactions have been reported in patients with quinolones. However, studies have shown that the risk of photosensitivity reactions induced by sunlight or ultraviolet radiation during treatment with moxifloxacin is reduced.
Patients with glucose-6-phosphate dehydrogenase deficiency
Patients with glucose-6-phosphate dehydrogenase deficiency, as well as patients with a family history of this pathology, are prone to developing hemolytic reactions during treatment with quinolones. Therefore, moxifloxacin should be used with caution in this category of patients.
Inflammation of tissues in the periarterial zone
Moxifloxacin solution for infusion is for intravenous use only. Intraarterial administration should be avoided as periarterial tissue inflammation has been observed in preclinical studies with this route of administration.
Patients with specific complicated skin and subcutaneous tissue infections
The clinical efficacy of moxifloxacin in the treatment of severe burn-related infections, fasciitis, and infected diabetic foot with osteomyelitis has not been established.
Impact on biological tests
Moxifloxacin may interfere with the results of tests for Mycobacterium spp. by inhibiting mycobacterial growth, which in turn may lead to false-negative results in patients taking moxifloxacin.
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). If MRSA infection is suspected or confirmed, treatment with an appropriate antibacterial agent should be initiated (see section 5.1).
Information on excipients
This medicinal product contains 787 mg (approximately 34 µmol) of sodium per vial containing 250 ml of solution for infusion, equivalent to 39.35% of the maximum daily intake of sodium (2 g) according to WHO recommendations for an adult.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effects of moxifloxacin on the ability to drive and use machines have not been conducted. However, fluoroquinolones, including moxifloxacin, may affect the speed of reactions when driving or operating other machines, causing central nervous system reactions (e.g. dizziness, acute temporary loss of vision) or acute and short-term loss of consciousness (syncope) (see section "Adverse reactions"). Patients are advised to check their reaction to moxifloxacin before driving or operating other machines.
Use during pregnancy or breastfeeding
Pregnancy
The safety of moxifloxacin during human pregnancy has not been studied. Animal studies have shown reproductive toxicity (see section 5.3). The potential risk to humans has not been established. Given the experimentally established risk of harmful effects of fluoroquinolones on weight-bearing cartilage in immature animals and the development of reversible joint lesions in children treated with some fluoroquinolones, moxifloxacin should not be administered to pregnant women (see section 4.3).
Breast-feeding
There are no data on the use of the drug during breastfeeding in women. The results of preclinical studies indicate that small amounts of moxifloxacin penetrate into breast milk. Due to the lack of data on the effects on breast-fed infants and taking into account the experimental risk of harmful effects of fluoroquinolones on the cartilage of immature animals that bear the main load, breastfeeding is contraindicated during treatment with moxifloxacin (see section "Contraindications").
Fertility
Animal studies have not shown any effect on fertility (see section 5.1).
Method of administration and doses
Dosage
The recommended dosage regimen is 400 mg of moxifloxacin as an infusion once daily.
Initial intravenous therapy may be continued with oral moxifloxacin tablets 400 mg if clinically indicated.
In clinical trials, most patients were switched to oral moxifloxacin within 4 days (communicable disease pneumonia) or 6 days (complicated skin and subcutaneous tissue infections). The recommended total duration of intravenous and oral treatment is 7–14 days for community-acquired pneumonia and 7–21 days for complicated skin and subcutaneous tissue infections.
Method of application
The drug should be administered intravenously as a continuous infusion lasting at least 60 minutes (see also the section "Special instructions for use").
If indicated, the infusion solution can be administered via a T-type catheter together with compatible infusion solutions (see section "Special precautions").
Renal/hepatic impairment
Patients with mild to severe renal impairment and patients on chronic dialysis, such as those undergoing haemodialysis and long-term ambulatory peritoneal dialysis, do not require dose adjustment (for more details see section 5.1).
There is insufficient information in patients with hepatic impairment (see section "Contraindications").
Other special patient groups
Elderly patients and patients with low body weight do not require dose adjustment.
Children
Due to the negative effect on the cartilage of young animals (see section "Pharmacological properties"), the use of moxifloxacin in children (under 18 years of age) is contraindicated (see section "Contraindications").
Effectiveness and safety of use
