Moxifloxacin film-coated tablets 400 mg blister No. 10

Instructions Moxifloxacin film-coated tablets 400 mg blister No. 10

Composition

active ingredient: moxifloxacin;

1 tablet contains 400 mg of moxifloxacin, as moxifloxacin hydrochloride;

excipients: microcrystalline cellulose; lactose, monohydrate; croscarmellose sodium; magnesium stearate; coating: hypromellose, polyethylene glycol 6000, titanium dioxide (E 171), iron oxide red (E 172)

Dosage form

Film-coated tablets.

Main physicochemical properties: oval-shaped tablets with a biconvex surface, covered with a pink shell.

Pharmacotherapeutic group

Antimicrobial agents for systemic use. Antibacterial agents of the quinolone group.

ATX code J01M A14.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

In vitro, moxifloxacin is effective against many Gram-positive and Gram-negative microorganisms. The bactericidal effect of moxifloxacin is due to the 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 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.

Pharmacodynamic studies indicate that 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 increased. The number of the above microorganisms returned to normal within two weeks.

Mechanism of 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 as a gradual process consisting of 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

Table 1

Clinical MICs and disk diffusion breakpoints for moxifloxacin (01.01.2012) according to EUCAST (European Committee on Antimicrobial Susceptibility Testing)

*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 were provided and are not used for species for which interpretive criteria are to be defined.

Microbiological susceptibility

The frequency of acquired resistance to certain species of microorganisms may vary depending on the geographical location of the region and over time. It is advisable to have access to local information on resistance of microorganisms, especially when treating serious infections. If necessary, advice from an expert in antibiotic resistance should be sought when the local prevalence of resistance is so high that the effectiveness of a particular drug against at least some types of infectious agents is questionable.

Sensitive species

Aerobic Gram-positive microorganisms

Gardnerella vaginalis

Staphylococcus aureus* (methicillin-susceptible)

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

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 taking single doses in the range of 50-800 mg and when using a dose of 600 mg per day for 10 days, the pharmacokinetics are linear. After taking an oral dose of 400 mg, the peak blood concentration is reached within 0.5-4 hours and is 3.1 mg/l. The maximum and minimum plasma concentrations at steady state (400 mg 1 time per day) 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.

Table 2

Peak concentration (geometric mean) after oral administration of a single dose of moxifloxacin 400 mg

*Intravenous administration of a single dose of 400 mg.

110 hours after administration.

2Free concentration.

3From 3 hours to 36 hours after dosing.

4At 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 sulfoconjugates (M1) and glucuronides (M2). M1 and M2 are the only metabolites relevant for humans, both of which are microbiologically inactive. In in vitro studies and phase I clinical studies, no metabolic pharmacokinetic interactions with other drugs involved in phase I biotransformation involving cytochrome P450 enzymes were observed. There is no evidence 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 faecal excretion (about 25% unchanged drug, about 36% M1 and no excretion as M2) was approximately 96%. Concomitant use of ranitidine and probenecid does not alter the renal clearance of the drug.

Elderly patients and patients with low body weight

Higher plasma concentrations of the drug were observed in healthy volunteers with low body weight (particularly 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 < 30 ml/min/1.73 m2).

Liver dysfunction

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

Use for the treatment of the following bacterial infections caused by microorganisms sensitive to moxifloxacin (see sections "Special instructions", "Adverse reactions", "Pharmacological properties"), in patients aged 18 years and older.

For the following indications, moxifloxacin should only be used when it is considered inappropriate to use other antibacterial agents that are usually recommended for the treatment of such infections:

• Acute bacterial sinusitis.
• Exacerbation of chronic obstructive pulmonary disease, including bronchitis.

For the following indications, moxifloxacin should only be prescribed when other antibacterial agents usually recommended for the initial treatment of such infections are inappropriate or have failed:

• 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 abscess. Moxifloxacin film-coated tablets 400 mg are not recommended for use as monotherapy in mild to moderate pelvic inflammatory disease, but may be used (except in cases of infection with moxifloxacin-resistant strains of Neisseria gonorrhoeae) in combination with other appropriate antibacterial agents (e.g. cephalosporins) due to the increasing resistance of Neisseria gonorrhoeae to moxifloxacin (see sections 4.4 and 5.1).

Moxifloxacin in tablet form can be used to complete a course of treatment in which initial therapy with the parenteral form of moxifloxacin was effective, for the following indications:

• community-acquired pneumonia;
• complicated infections of the skin and subcutaneous structures.

Moxifloxacin in tablet form is not recommended for initial treatment of any skin and subcutaneous infections or in severe community-acquired pneumonia.

Official guidelines on the appropriate use of antibacterial agents should be taken into account.

Contraindication

• Hypersensitivity to moxifloxacin or to other quinolones or to any of the excipients of the medicinal product.
• Age up to 18 years.
• Pregnancy or breast-feeding (see section “Use during pregnancy or breast-feeding”).
• History of tendon diseases associated with quinolone treatment.

In preclinical and clinical studies, changes in cardiac electrophysiology in the form of prolongation of the QT interval were observed after the use of moxifloxacin. Therefore, for safety reasons, the drug is contraindicated in patients with:

• congenital or diagnosed acquired QT prolongation;
• electrolyte imbalance, particularly uncorrected hypokalemia;
• clinically significant bradycardia;
• clinically significant heart failure with reduced left ventricular ejection fraction;
• history of symptomatic arrhythmias.

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 can 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 antiarrhythmic drugs (e.g. quinidine, hydroquinidine, disopyramide);
• class III antiarrhythmic drugs (e.g. amiodarone, sotalol, dofetilide, ibutilide);
• antipsychotic drugs (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride);
• tricyclic antidepressants;
• certain antimicrobials (saquinavir, sparfloxacin, intravenous erythromycin, pentamidine, antimalarials, including halofantrine);
• some antihistamines (terfenadine, astemizole, mizolastine);
• others (cisapride, vincamine IV, bepridil, diphemanil).

Moxifloxacin should be administered with caution to patients taking drugs that may lower potassium levels (e.g. loop and thiazide diuretics, enemas and laxatives (in high doses), corticosteroids, amphotericin B), or drugs whose effects are associated with clinically significant bradycardia.

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% was observed without any effect on AUC (area under the concentration-time curve) or trough concentrations. 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 cases 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 inflammatory process), advanced age and poor general condition of the patient. In these circumstances, it is difficult to assess whether the infection or the treatment is causing the INR deviation. More frequent monitoring of the INR may be appropriate. If necessary, appropriate adjustment of the oral anticoagulant dose should be made.

Substances for which the absence of clinically significant interactions with moxifloxacin has been proven: ranitidine, calcium supplements, theophylline, oral contraceptives, cyclosporine, itraconazole, parenteral morphine, probenecid.

In vitro studies of human cytochrome P450 enzymes confirmed the above. Thus, metabolic interactions via cytochrome P450 enzymes are unlikely.

The absorption of moxifloxacin is independent of food intake (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 may increase the QT interval on the electrocardiogram in some patients. Analysis of ECG data obtained in the clinical trial program 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-associated effects on the QT interval.

Patients taking moxifloxacin should be cautious when using drugs that may cause a decrease in potassium levels (see sections “Contraindications”, “Interaction with other medicinal products and other types of interactions”).

Moxifloxacin should be administered with caution to patients with ongoing proarrhythmic conditions (especially women and the elderly), such as acute myocardial ischemia or QT prolongation, as this increases the risk of ventricular arrhythmias, including torsade de pointes, and cardiac arrest (see section 4.3). The extent of QT prolongation may increase with increasing drug concentrations. Therefore, the recommended dose should not be exceeded.

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 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 therapy (e.g. anti-shock) should be initiated.

Cases of fulminant hepatitis, which may lead to hepatic failure (including fatal cases), 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 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 may 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 symptoms suggestive of such reactions occur, 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 treatment with moxifloxacin, 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 central nervous system (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 (several 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 age or risk factors. Moxifloxacin should be discontinued immediately at the first sign of any serious adverse reaction and patients should be advised to seek medical advice.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy resulting in paresthesias, hypoesthesias, dysesthesias 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 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 psychiatric disorders or a history of such 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.

During therapy with quinolones and fluoroquinolones, inflammation and tendon ruptures (especially of the Achilles tendon), sometimes bilateral, may occur, developing within 48 hours of starting treatment and may occur even up to several months after stopping treatment (see sections "Contraindications" and "Adverse Reactions"). The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal insufficiency, patients with solid organ transplants and in patients receiving concomitant treatment with corticosteroids. Therefore, concomitant use with corticosteroids should be avoided.

At the first signs of tendinitis (e.g. painful swelling, inflammation), moxifloxacin should be discontinued and alternative therapy considered. Appropriate treatment (e.g. immobilization) should be provided for the affected limb. Corticosteroids should not be used if symptoms of tendinopathy develop.

Aortic aneurysm and aortic dissection, regurgitation/valvular insufficiency

Epidemiological studies have shown an increased risk of aortic aneurysm and aortic wall dissection, especially 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 cases of 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 with valvular heart disease, and in the presence of other risk factors:

— conditions that contribute to the development of both aortic aneurysm and aortic wall dissection, and regurgitation/valvular insufficiency: connective tissue disorders such as Marfan syndrome or vascular Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, arterial hypertension, rheumatoid arthritis;

— conditions that contribute to the development of aortic aneurysm and its dissection: vascular disorders such as Takayasu arteritis or giant cell arteritis, atherosclerosis, Sjögren's syndrome;

— conditions that contribute to the development of regurgitation/valvular insufficiency: infective endocarditis.

The risk of developing aortic aneurysm and dissection, as well as aortic rupture, is 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 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 concomitant oral hypoglycemic agents (e.g. sulfonylureas) or insulin during moxifloxacin treatment. 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 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 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.

Patients with pelvic inflammatory disease

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 reconsidered.

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 infected diabetic foot with osteomyelitis has not been established.

Impact on biological tests

Treatment with moxifloxacin may interfere with microbiological testing for Mycobacterium spp. due to inhibition of mycobacterial growth, which in turn may lead to false-negative results in samples from patients currently 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). In case of suspected or confirmed MRSA infection, treatment with an appropriate antibacterial agent should be initiated (see section 5.1).

Children

Moxifloxacin causes cartilage damage in young animals (see section "Pharmacological properties"), therefore the use of the drug in children (under 18 years of age) is contraindicated (see section "Contraindications").

Information on excipients

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, i.e. essentially 'sodium-free'.

Use during pregnancy or breastfeeding

Pregnancy

The safety of moxifloxacin during pregnancy has not been established.

Animal studies have shown reproductive toxicity (see section 5.1). The potential risk to humans has not been established.

Due to the identified 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").

Breastfeeding

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 be excreted in 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 (see section 5.1).

The ability to influence the 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 cause central nervous system reactions such as dizziness, acute transient loss of vision, or acute transient loss of consciousness (see section 4.8), thereby impairing the ability to drive and use machines. Patients should be advised to observe their reaction to moxifloxacin before driving or operating machines.

Sp