Moxicum tablets 400 mg No. 7

Instructions for use Moxicum tablets 400 mg No. 7

Composition

active ingredient: moxifloxacin;

1 film-coated tablet contains moxifloxacin (as moxifloxacin hydrochloride) 400 mg;

excipients: microcrystalline cellulose (PH 102); sodium starch glycolate (type A); mannitol (E 421); magnesium stearate;

film coating Opadry® Pink 85F240036 (polyvinyl alcohol; titanium dioxide (E 171); macrogol; talc; iron oxide red (E 172); iron oxide yellow (E 172)).

Dosage form

Film-coated tablets.

Main physicochemical properties: biconvex oblong tablets, coated with a pink film coating.

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 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.

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 well as the anaerobes Bacteroides vulgatus, Bifidobacterium spp., Eubacterium and Peptostreptococcus. An increase in the number of Bacteroides fragilis was observed. The number of the above microorganisms returned to normal within 2 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 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 susceptible 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

* 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 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

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)

Aerobic Gram-negative microorganisms

Acinetobacter baumanii

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 with possible acquired 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.

Preclinical safety data.

Effects on the hematopoietic system (slight reduction in the number of erythrocytes and platelets) were observed in rats and monkeys. As with other quinolones, hepatotoxicity (elevated liver enzymes and vacuolar degradation) was observed in rats, monkeys and dogs. Cases of neurotoxicity (CNS damage - convulsions) were recorded in monkeys. These effects were observed only after taking high doses of moxifloxacin or after its long-term use.

Moxifloxacin, like other quinolones, has shown genotoxicity in in vitro tests with bacteria or mammalian cells. Since this effect is explained by interaction with bacterial gyrase and, at higher concentrations, with topoisomerase II in mammalian cells, it can be assumed that there is a threshold concentration for genotoxicity. In vivo tests did not reveal any signs of genotoxicity, despite the use of high doses of moxifloxacin. Thus, moxifloxacin has shown sufficient safety potential when used in therapeutic doses for humans. Moxifloxacin did not show a carcinogenic effect in a study conducted in rats.

Many quinolones are photoreactive and can provoke phototoxic reactions, exhibit photomutagenic and photocarcinogenic effects. At the same time, there is evidence of the absence of phototoxic and photogenotoxic properties in moxifloxacin when tested within the framework of a comprehensive program of in vitro and in vivo studies. Under the same conditions, quinolones demonstrated the indicated effects.

At high concentrations, moxifloxacin acts as an inhibitor of the fast component of the cardiac slow component of the cardiac rectifier potassium current and may therefore lead to QT prolongation. Toxicological studies in dogs, in which moxifloxacin was administered orally at doses ≥ 90 mg/kg, resulting in concentrations ≥ 16 mg/l, showed QT prolongation without arrhythmias. Reversible non-fatal ventricular arrhythmias were observed only after intravenous administration of a high cumulative dose, which was more than 50 times the human dose (> 300 mg/kg), resulting in plasma concentrations ≥ 200 mg/l (more than 40 times the therapeutic level).

Quinolones are known to cause cartilage damage in large diarthrodial joints in young animals. The lowest oral dose of moxifloxacin that resulted in arthrotoxic effects in young dogs was four times the maximum recommended therapeutic dose of 400 mg (based on 50 kg body weight) calculated on a dose/body weight (mg/kg) basis, with plasma concentrations two to three times higher than those expected at the maximum therapeutic dose.

Toxicity tests conducted in rats and monkeys (repeated administration for up to 6 months) did not reveal any signs of risk to the eyes. In studies in dogs, only high oral doses (≥ 60 mg/kg) resulted in plasma concentrations ≥ 20 mg/l, which caused changes in the electroretinogram and in some cases led to retinal atrophy.

In the study of the effect of moxifloxacin on the reproductive function of animals, it was proven that moxifloxacin penetrates the placenta. Experiments conducted on rats (when using moxifloxacin orally and intravenously) and monkeys (when using moxifloxacin orally) did not reveal the teratogenic effect of moxifloxacin and its effect on fertility. When using moxifloxacin intravenously at a dose of 20 mg/kg in rabbits, skeletal malformation was observed. An increase in the number of miscarriages was found in monkeys and rabbits when using moxifloxacin in a therapeutic dose. In rats, a decrease in fetal weight, an increase in the incidence of miscarriages, a slight increase in the duration of the gestation period and an increase in spontaneous activity of the offspring were observed when using moxifloxacin, the dosage of which was 63 times higher than the recommended.

Pharmacokinetics.

Absorption and bioavailability

In the dose range of 50-800 mg in a single dose and at 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 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

* 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 state and in the form of inactive sulfo compounds (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 agents involved in phase I biotransformation involving cytochrome P450 enzymes were observed. There is no evidence of oxidative metabolism.

Breeding

The half-life of moxifloxacin is approximately 12 hours. The mean total clearance after administration of a 400 mg dose is 179 to 246 ml/min. Renal clearance is approximately 24–53 ml/min, indicating partial tubular reabsorption from the kidneys. After administration of a 400 mg dose, urinary (about 19% unchanged, about 2.5% M1 and about 14% M2) and faecal (about 25% unchanged, about 36% M1 and no excretion as M2) excretion was approximately 96%. Concomitant administration of ranitidine and probenecid does not alter the renal clearance of moxifloxacin.

Elderly patients and patients with low body weight

Higher plasma concentrations of moxifloxacin were observed in healthy volunteers with low body weight (particularly women) and in healthy elderly volunteers.

Patients with renal impairment

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).

Patients with hepatic impairment

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 microorganisms susceptible 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 used when other antibacterial agents usually recommended for the initial treatment of the following infections are inappropriate or when such treatment has been ineffective:

community-acquired pneumonia (except severe community-acquired pneumonia);

The tablet form of moxifloxacin is not recommended for use as monotherapy for mild to moderate pelvic inflammatory disease, but can be used in combination with other appropriate antibacterial agents (e.g. cephalosporins) due to the increasing resistance of Neisseria gonorrhoeae to moxifloxacin (with the exception of moxifloxacin-resistant strains of Neisseria gonorrhoeae) (see sections "Special instructions", "Pharmacological properties").

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

community-acquired pneumonia;

complicated infections of the skin and subcutaneous structures.

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

Attention should be paid to official instructions on the proper use of antibacterial agents.

Contraindication

Hypersensitivity to moxifloxacin, other quinolones or to any of the other ingredients of the drug.

History of tendon diseases/disorders associated with quinolone treatment.

Concomitant use with drugs that prolong the QT interval (see section "Interaction with other medicinal products and other types of interactions").

Liver dysfunction (Child-Pugh class C), increased transaminase levels (5 times the upper limit of normal).

Children under 18 years of age.

Pregnancy (see section "Use during pregnancy or breastfeeding").

Breastfeeding (see section "Use during pregnancy or breastfeeding").

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 prolongation of the QT interval;

with electrolyte imbalance, in particular with uncorrected hypokalemia;

with clinically significant bradycardia;

with clinically significant heart failure with reduced left ventricular ejection fraction;

with a history of symptomatic arrhythmias.

Interaction with other medicinal products and other types of interactions

Agents that may cause QT prolongation

An additive effect of moxifloxacin and other medicinal products that can prolong the QT interval cannot be excluded. This interaction may lead to an increased 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 section 4.3):

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;

certain antimicrobials (saquinavir, sparfloxacin, intravenous erythromycin, pentamidine, antimalarials, including halofantrine);

some antihistamines (terfenadine, astemizole, mizolastine);

others (cisapride, vincamine for intravenous administration, bepridil, diphemanil).

Drugs that may lower potassium levels (e.g. loop and thiazide diuretics, high-dose enemas and laxatives, corticosteroids, amphotericin B), drugs that are associated with clinically significant bradycardia.

Caution should be exercised when using moxifloxacin with such agents.

Agents containing divalent or trivalent cations (such as antacids containing magnesium or aluminum, didanosine in tablet form, sucralfate, and agents containing iron or zinc)

An interval of approximately 6 hours is required between taking agents containing divalent or trivalent cations (such as antacids containing magnesium or aluminum, didanosine tablets, sucralfate, and agents containing iron or zinc) and moxifloxacin.

Activated carbon

When activated charcoal is administered orally with moxifloxacin at a dose of 400 mg, its systemic bioavailability is reduced by more than 80% due to inhibition of absorption. Therefore, the simultaneous use of these agents is not recommended (except in cases of overdose, see section "Overdose").

Oral anticoagulants

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 INR deviation. 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.

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 these drugs simultaneously.

Glibenclamide

In studies in diabetic volunteers, concomitant oral administration of moxifloxacin and glibenclamide resulted in a decrease in the maximum concentration of the latter by approximately 21%. Concomitant administration 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.

Agents 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. Given these results, metabolic interaction via cytochrome P450 enzymes is unlikely.

The absorption of moxifloxacin is independent of food intake (including dairy products).

Impact on research

Treatment with moxifloxacin may interfere with culture assays for Mycobacterium spp. due to inhibition of microbial growth, which in turn may lead to false-negative results in samples from patients currently taking moxifloxacin.

Application features

The benefits of treatment with moxifloxacin should be weighed against those of mild infections, especially in accordance with the information provided in the section "Special warnings and precautions for use".

The drug should be avoided in patients with a history of serious adverse reactions to quinolone or fluoroquinolone-containing drugs (see section "Adverse reactions"). Treatment of such patients should only be initiated in the absence of alternative treatment and after a careful benefit/risk assessment (see also section "Contraindications").

Prolonged, disabling and potentially irreversible serious adverse reactions

When using quinolones and fluoroquinolones, cases of prolonged (months or years), disabling and potentially irreversible serious adverse reactions from different, sometimes multiple, body systems (musculoskeletal, nervous system, mental and sensory organs) have been reported very rarely, regardless of age and the presence of risk factors. In case of the development of the first symptoms and signs of any serious adverse reaction, the drug should be discontinued immediately and a doctor should be consulted.

Aortic aneurysm/dissection and heart valve regurgitation/insufficiency.

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. Rare cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and of regurgitation/insufficiency of any of the heart valves have been reported in patients receiving fluoroquinolones (see section "Adverse reactions").

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/heart 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 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/valve 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.

QTc prolongation and clinical conditions potentially associated with QTc prolongation

Because 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 QT effects.

The drug should be used with caution in patients taking medications that may lead to a decrease in potassium levels (see sections "Contraindications", "Interaction with other medicinal products and other types of interactions").

The drug should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients), such as acute myocardial ischemia or QT prolongation, as this may lead to an increased risk of ventricular arrhythmias, including torsade de pointes, and cardiac arrest (see section "Contraindications").

The degree of QT prolongation may increase with increasing drug concentration. Therefore, the recommended dose should not be exceeded.

If symptoms of arrhythmia occur during use of the drug, treatment should be discontinued and an ECG should be performed.

Hypersensitivity reactions

Hypersensitivity and allergic reactions have been reported with fluoroquinolones, including moxifloxacin, after initial administration. Anaphylactic reactions may progress to life-threatening anaphylactic shock even after the first dose. In such cases, the drug should be discontinued and appropriate therapy (e.g. anti-shock) 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 signs and symptoms of fulminant hepatitis develop, such as rapidly progressive asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, patients should consult a doctor before continuing treatment. Liver function tests/examination should be performed if symptoms of liver dysfunction occur.

Severe skin lesions

Severe skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN, also called Lyell's syndrome), and acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported with moxifloxacin (see section 4.8). Patients should be informed of the signs and symptoms of serious skin reactions and monitored closely before starting treatment. If symptoms and signs consistent with these reactions develop, the drug should be discontinued immediately and alternative treatment should be considered. If serious reactions such as SJS, TEN, or AGEP occur with moxifloxacin, moxifloxacin should not be restarted at any time in the future.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia, hypoesthesia, dysesthesia or weakness have been reported with quinolones, including moxifloxacin. To prevent potentially irreversible damage, patients should consult a doctor if they develop symptoms of neuropathy such as pain, burning, tingling, numbness or weakness (see section 4.8).

Mental reactions

When using quinolones, including moxifloxacin, psychiatric reactions are possible even after the first use. In rare cases, depression or psychotic reactions have led to the emergence of suicidal thoughts and the development of self-harm, including suicide attempts (see section "Adverse reactions"). If such reactions develop, the drug should be discontinued and appropriate measures should be taken. The drug should be used with caution in patients suffering from psychosis or in patients with a history of mental illness.

Antibiotic-associated diarrhea (AAD), 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 this diagnosis in patients who develop severe diarrhea during or after drug administration. If AAD or AAC is suspected or confirmed, treatment with antibacterial agents, including moxifloxacin, should be discontinued and appropriate therapeutic measures should be taken immediately. In addition, appropriate sanitary and epidemiological measures should be taken to reduce the risk of disease transmission. Antimicrobial agents are contraindicated in patients with severe diarrhea.

Tendonitis and tendon rupture (especially of the Achilles tendon), sometimes bilateral, have been reported with quinolones, including moxifloxacin, even within the first 48 hours of administration. Cases have also been reported several months after discontinuation of treatment (see sections 4.3 and 4.8). There is an increased risk of tendon inflammation and rupture during treatment with quinolones, including moxifloxacin, particularly in the elderly, patients with renal impairment, patients with solid organ transplants and patients receiving concomitant corticosteroid therapy. The drug should be avoided in such patients.

At the first signs of tendinitis (painful swelling, inflammation), the medicinal product should be discontinued and alternative treatments considered. Appropriate treatment of the affected limb(s) should be initiated (e.g. immobilization) (see sections 4.3 and 4.8). Corticosteroids should not be used if symptoms of tendinopathy develop.

Vision impairment

In case of visual disturbances or other effects on the organs of vision, you should immediately consult an ophthalmologist (see sections “Ability to influence the speed of reactions when driving vehicles or operating other mechanisms”, “Adverse reactions”).

Dysglycemia

As with other fluoroquinolones, abnormalities in plasma glucose levels, including hypoglycemia and hyperglycemia, have been observed with moxifloxacin (see section 4.8). Dysglycemia has occurred predominantly in elderly patients with diabetes mellitus receiving concomitant oral hypoglycemic agents (e.g. sulfonylureas) or insulin. Cases of hypoglycemic coma have been reported. Close monitoring of plasma glucose levels is recommended in diabetic patients when using the drug.

Photosensitivity reactions

Photosensitivity reactions are possible with quinolones. However, studies have shown that moxifloxacin has a lower risk of such reactions. Despite this, both ultraviolet radiation and prolonged and/or intense exposure to sunlight should be avoided during use of the drug.

Use in patients prone to seizures

Quinolones are known to induce seizures. The drug 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, the drug should be discontinued and appropriate measures taken.

Use in patients with severe myasthenia gravis

Moxifloxacin should be used with caution in patients with myasthenia gravis, as its symptoms may be exacerbated.

Use in patients with renal impairment

The drug should be used with caution in elderly patients with kidney function disorders if they cannot ensure adequate fluid intake, as dehydration may increase the risk of kidney failure.

Use in patients with insufficient glucose-6-phosphate dehydrogenase activity

Patients with a family or personal history of glucose-6-phosphate dehydrogenase deficiency are more likely to develop hemolytic reactions when treated with quinolones. The drug should be used with caution in such patients.

Use in patients with pelvic inflammatory disease

Patients with complicated pelvic inflammatory disease (e.g.