Avelox

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AVELOX® (AVELOX®)

Composition:

Active substance: moxifloxacin;

1 vial (250 ml of solution) contains 436 mg of moxifloxacin hydrochloride, corresponding to
400 mg of moxifloxacin;

Excipients: sodium chloride, hydrochloric acid diluted, sodium hydroxide, water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear yellow-colored solution.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Antibacterial agents of the quinolone group. ATC code J01MA14.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Moxifloxacin inhibits bacterial type II topoisomerases (DNA gyrase and topoisomerase IV), which are essential for replication, transcription, and repair of bacterial DNA.

Pharmacokinetics/pharmacodynamics

The ability of fluoroquinolones to kill bacteria is directly concentration-dependent. Pharmacodynamic studies of fluoroquinolones in animal models of infectious-inflammatory diseases and in humans indicate that the primary 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 may arise due to mutations in DNA gyrase and topoisomerase IV. Other mechanisms include overexpression of efflux pumps, impermeability, and protein-mediated protection of DNA gyrase. Cross-resistance may be expected between moxifloxacin and other fluoroquinolones.

Resistance mechanisms characteristic of antibacterial agents belonging to other classes do not affect the antibacterial efficacy of moxifloxacin.

Breakpoints

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

Table 1

*Non-species-related breakpoints were primarily established based on the relationship between pharmacokinetic and pharmacodynamic data and do not depend on the MICs of individual species. These data are used for species lacking individually defined breakpoints and do not apply to species for which interpretive criteria are to be determined.

Microbiological susceptibility

The prevalence of acquired resistance in isolated species may vary geographically and over time; therefore, local information on resistance patterns is necessary, especially when treating severe infections. If necessary, consultation with specialists should be sought when local resistance prevalence has reached a level at which the benefit of using the medicinal product is questionable, at least for certain types of infections.

Pharmacokinetics.

Absorption and Bioavailability

After a single 1-hour intravenous infusion of 400 mg, the maximum concentration of the drug is reached at the end of the infusion and is approximately 4.1 mg/L, which is about 26% higher than that observed after oral administration (3.1 mg/L). The AUC is approximately 39 mg*h/L following intravenous administration, slightly exceeding the value after oral administration (35 mg*h/L); the absolute bioavailability is approximately 91%. With intravenous administration of moxifloxacin, no dose adjustment is required based on patient age or gender. The pharmacokinetics are linear within the range of 50–200 mg for single oral doses, up to 600 mg for single intravenous doses, and up to 600 mg administered once daily for 10 days.

Distribution

Moxifloxacin rapidly distributes into the extravascular space. The volume of distribution at steady state (Vss) is approximately 2 L/kg. In vitro and ex vivo studies indicate that protein binding is approximately 40–42%, independent of drug concentration. Moxifloxacin binds primarily to serum albumin.

Maximum concentrations of 5.4 mg/kg and 20.7 mg/L (geometric mean values) were observed in bronchial mucosa and epithelial lining fluid, respectively, 2.2 hours after oral administration. The corresponding maximum concentration in alveolar macrophages was 56.7 mg/kg. A concentration of 1.75 mg/L was observed in skin blister fluid 10 hours after intravenous administration. The "free concentration–time" profile in interstitial fluid is similar to that in plasma, with a maximum free concentration of 1.0 mg/L (geometric mean) reached approximately 1.8 hours after intravenous administration.

Metabolism

Moxifloxacin undergoes phase II biotransformation and is eliminated via the kidneys (approximately 40%) and feces/bile (approximately 60%) both unchanged and as sulfate conjugate (M1) and glucuronide (M2). M1 and M2 are metabolites relevant only in humans; both are microbiologically inactive.

In vitro studies and Phase I clinical trials have shown no evidence of metabolic pharmacokinetic interactions with other drugs involved in phase I biotransformation, including cytochrome P450 enzyme systems. There is no indication of oxidative metabolism.

Elimination

The elimination half-life of moxifloxacin in plasma is approximately 12 hours. The mean steady-state total clearance after administration of 400 mg ranges from 179 to 246 mL/min. After a 400 mg intravenous dose, approximately 22% of the drug is excreted unchanged in urine and 26% in feces. Overall excretion (unchanged drug and metabolites) totals approximately 98% after intravenous administration. Renal clearance is approximately 24–53 mL/min, indicating partial tubular reabsorption of the drug in the kidneys. Concomitant administration of ranitidine and probenecid does not alter the renal clearance of the parent drug.

Renal Impairment

No significant changes in moxifloxacin pharmacokinetics have been observed in patients with renal impairment (including patients with creatinine clearance > 20 mL/min/1.73 m²). As renal function declines, the concentration of metabolite M2 (glucuronide) increases by almost 2.5-fold (with creatinine clearance < 30 mL/min/1.73 m²).

Hepatic Impairment

Pharmacokinetic data from studies involving patients with hepatic impairment (Child–Pugh classes A and B) do not allow definitive conclusions regarding differences in pharmacokinetic parameters between patients with hepatic impairment and healthy volunteers. Hepatic impairment was associated with increased plasma exposure to metabolite M1, while exposure to the parent drug was similar to that in healthy volunteers. There is insufficient clinical experience with moxifloxacin to recommend its use in patients with hepatic impairment.

Preclinical Safety Data

In traditional repeat-dose toxicity studies in animals, moxifloxacin demonstrated hematological toxicity and hepatotoxicity. Toxic effects on the central nervous system (CNS) were also observed. These effects occurred after administration of high doses of moxifloxacin or with prolonged treatment.

High oral doses in animals (≥ 60 mg/kg), resulting in plasma concentrations ≥ 20 mg/L, caused changes in electroretinogram parameters and, in some cases, retinal atrophy.

Systemic toxicity after intravenous administration was most pronounced when moxifloxacin was given as bolus injections (45 mg/kg) and was not observed when administered as slow infusions (40 mg/kg) over 50 minutes.

After intra-arterial administration, inflammatory changes extending into periarterial soft tissues were observed, indicating that intra-arterial administration of moxifloxacin should be avoided.

Moxifloxacin was genotoxic in vitro in tests using bacteria or mammalian cells. However, no genotoxicity was observed in vivo, even with very high doses of moxifloxacin. Moxifloxacin showed no carcinogenic potential in animal carcinogenicity studies.

In vitro, high concentrations of moxifloxacin affected cardiac electrophysiological parameters, potentially leading to QT interval prolongation.

After intravenous administration of moxifloxacin to animals at a dose of 30 mg/kg via infusions lasting 15, 30, or 60 minutes, a relationship between the degree of QT prolongation and infusion rate was observed: the shorter the infusion duration, the more pronounced the QT prolongation. QT prolongation was not observed when the 30 mg/kg dose was administered over 60 minutes.

Studies on the effects of moxifloxacin on animal reproductive function have demonstrated that moxifloxacin crosses the placenta. Animal studies did not reveal teratogenic effects or impaired fertility after moxifloxacin administration. Slight increases in the incidence of spinal and rib malformations were observed in animals, but only after administration of a dose (20 mg/kg intravenously) associated with severe maternal toxicity. Increased rates of pregnancy loss were observed in animals at plasma concentrations corresponding to therapeutic levels expected in humans.

It is known that quinolones, including moxifloxacin, can cause cartilage damage in the large diarthrodial joints of immature animals.

Clinical characteristics.

Indications.

Community-acquired pneumonia.

Complicated skin and soft tissue infections.

Moxifloxacin should only be used when the use of other antibacterial agents normally recommended for initial treatment of these infections is inappropriate.

Attention should be paid to official guidelines on the appropriate use of antibacterial agents.

Contraindications.

• Hypersensitivity to moxifloxacin, other quinolone antibiotics, or any of the excipients;
• Pregnancy or breastfeeding (see section "Use in pregnancy or breastfeeding");
• Paediatric age (under 18 years);
• History of tendon disorders related to the use of quinolones.

During preclinical and clinical studies, changes in cardiac electrophysiological parameters, manifested as QT interval prolongation, were observed after administration of moxifloxacin. For this reason, moxifloxacin is contraindicated in patients with:

• Congenital or acquired QT interval prolongation;
• Electrolyte imbalance, particularly uncorrected hypokalaemia;
• Clinically significant bradycardia;
• Clinically significant heart failure with reduced left ventricular ejection fraction;
• History of symptomatic arrhythmias.

Moxifloxacin must not be administered concomitantly with drugs known to prolong the QT interval (see also section "Interaction with other medicinal products and other forms of interaction").

Due to insufficient clinical experience, moxifloxacin is contraindicated in patients with hepatic impairment (Child–Pugh class C) and in those with transaminase elevations five times or more above the upper limit of normal.

Interaction with other medicinal products and other forms of interaction.

Interaction with medicinal products

An additive effect of moxifloxacin and other medicinal products capable of inducing QTc interval prolongation cannot be excluded. This effect may lead to the development of ventricular arrhythmias, including torsades de pointes. Therefore, the use of moxifloxacin in combination with any of the following medicinal products is contraindicated (see also section "Contraindications"):

• Class IA antiarrhythmic agents (e.g. quinidine, hydroquinidine, disopyramide);
• Class III antiarrhythmic agents (e.g. amiodarone, sotalol, dofetilide, ibutilide);
• Antipsychotic agents (e.g. phenothiazines, pimozide, sertindole, haloperidol, sulpiride);
• Tricyclic antidepressants;
• Certain antimicrobial agents (saquinavir, sparfloxacin, intravenous erythromycin, pentamidine, antimalarials including halofantrine);
• Certain antihistamines (terfenadine, astemizole, mizolastine);
• Other medicinal products (cisapride, intravenous vincamine, bepridil, difemelane).

Moxifloxacin should be used with caution in patients receiving medicinal products that may reduce potassium levels (e.g. loop and thiazide diuretics, laxatives and enemas (at high doses), corticosteroids, amphotericin B), or agents associated with clinically significant bradycardia.

Following multiple doses of moxifloxacin in healthy volunteers, an increase in digoxin Cmax of approximately 30% was observed, without affecting AUC or trough levels.

In studies involving volunteers and diabetic patients, concomitant oral administration of moxifloxacin and glyburide (glibenclamide) resulted in a reduction of glyburide plasma maximum concentration by approximately 21%. The combination of glyburide with moxifloxacin may theoretically provoke mild, short-term hyperglycaemia. However, the observed changes in glyburide pharmacokinetics did not result in changes in pharmacodynamic parameters (blood glucose levels, insulin levels). Therefore, there is no clinically significant interaction between moxifloxacin and glyburide.

Change in International Normalised Ratio (INR).

Numerous cases of increased activity of oral anticoagulants have been reported in patients receiving antimicrobial agents, particularly fluoroquinolones, macrolides, tetracyclines, co-trimoxazole and certain cephalosporins. Contributing factors include infection and inflammatory processes, age and general condition of the patient. Therefore, it is difficult to determine whether changes in INR are due to the infection or the treatment. As a precautionary measure, INR should be monitored more frequently. Dose adjustment of the oral anticoagulant should be performed as necessary.

In clinical studies, the following substances have been shown not to have a clinically significant interaction with moxifloxacin: ranitidine, probenecid, oral contraceptives, calcium supplements, parenterally administered morphine, theophylline, cyclosporine or itraconazole.

In vitro studies using human cytochrome P450 enzymes have confirmed these results. Therefore, metabolic interaction via cytochrome P450 enzymes is unlikely.

Interaction with food

Moxifloxacin does not exhibit clinically significant interaction with food, including dairy products.

Special precautions for safety.

Each vial is intended for single use only. Any unused solution must be discarded.

The following diluents have been shown to be compatible with the 400 mg moxifloxacin infusion solution: water for injection; 0.9% sodium chloride solution; 1-molar sodium chloride solution; 5%, 10%, 40% glucose solutions; 20% xylose solution; Ringer's solution; compound sodium lactate solutions (Hartmann's solution, lactated Ringer's solution).

Moxifloxacin infusion solution must not be administered simultaneously with other medicinal products.

Do not use the medicinal product if visible particulate matter is present or if the solution is cloudy.

Precipitation may occur upon storage in a cool place, but the precipitate dissolves at room temperature. Therefore, storage of the infusion solution below 15°C is not recommended.

Special precautions for use.

The use of moxifloxacin should be avoided in patients with a history of serious adverse reactions after treatment with medicinal products containing quinolones or fluoroquinolones (see section "Adverse reactions"). Treatment with moxifloxacin in such patients should be initiated only if no alternative therapy is available and after careful evaluation of the benefit-risk ratio (see also section "Contraindications").

The benefits of moxifloxacin therapy, particularly in cases of mild infections, should be carefully weighed against the information provided in this section.

QTc interval prolongation and clinical conditions associated with potential QTc interval prolongation

Therapy with moxifloxacin should be discontinued if symptoms occur that may be associated with cardiac arrhythmia, regardless of whether this is confirmed by ECG findings.

Moxifloxacin should be used with caution in patients with conditions predisposing to arrhythmia (e.g., acute myocardial ischemia), as such patients have an increased risk of developing ventricular arrhythmia (including polymorphic ventricular tachycardia such as torsade de pointes) and cardiac arrest (see also sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction"). Moxifloxacin should be used with caution in patients receiving medicinal products that may reduce potassium levels (see also sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction").

Moxifloxacin should be used with caution in patients receiving medicinal products associated with clinically significant bradycardia (see also section "Contraindications").

Women and elderly patients may exhibit increased sensitivity to the effects of drugs that prolong the QTc interval, such as moxifloxacin; therefore, such patients require special attention.

Increased sensitivity/allergic reactions

Cases of hypersensitivity and allergic reactions have been reported after the first dose of fluoroquinolones, including moxifloxacin. Anaphylactic reactions may manifest as life-threatening shock even after the first dose of the drug. In case of clinical manifestations of severe hypersensitivity reactions, moxifloxacin should be discontinued and appropriate treatment initiated (e.g., shock therapy).

Severe hepatic impairment

Cases of fulminant hepatitis have been reported during moxifloxacin therapy, which may lead to hepatic failure (including fatal cases) (see section "Adverse reactions"). If symptoms of fulminant hepatitis occur, such as rapidly developing asthenia accompanied by jaundice, dark urine, bleeding tendency, or hepatic encephalopathy, patients are advised to consult a physician before continuing treatment.

Liver function tests should be performed if signs of hepatic impairment occur.

Severe skin reactions

Cases of severe skin reactions, including toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during moxifloxacin therapy (see section "Adverse reactions"), which may be life-threatening or fatal. Patients should be warned about signs and symptoms of severe skin reactions and carefully monitored. Moxifloxacin should be immediately discontinued and alternative treatment considered if signs and symptoms suggestive of such reactions occur. Moxifloxacin therapy should never be resumed in patients who have developed severe skin reactions such as SJS, TEN, AGEP, or DRESS during treatment with moxifloxacin.

Patients predisposed to seizures

Quinolones are known to induce seizures. They should be used with caution in patients with CNS disorders or other risk factors that may provoke seizures or lower the seizure threshold. If seizures occur, moxifloxacin should be discontinued and appropriate measures taken.

Prolonged, disabling, and potentially irreversible serious adverse reactions

Rare cases of prolonged (lasting months or years), disabling, and potentially irreversible serious adverse reactions affecting various, sometimes multiple organ systems (musculoskeletal, nervous, psychiatric, and sensory organs) have been reported in patients receiving quinolones and fluoroquinolones, regardless of patient age or existing risk factors. Moxifloxacin should be immediately discontinued at the onset of any serious adverse reaction, and patients should be advised to consult a physician.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hyposthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Patients receiving moxifloxacin should be advised to inform their physician of any neuropathic symptoms such as pain, burning, tingling, numbness, or weakness before continuing treatment to prevent potentially irreversible conditions (see section "Adverse reactions").

Psychiatric reactions

Psychiatric reactions may occur even after the first dose of fluoroquinolones, including moxifloxacin. In rare cases, depression or psychiatric reactions have progressed to suicidal thoughts and self-harming behaviors such as suicide attempts (see section "Adverse reactions"). If such reactions occur, moxifloxacin therapy should be discontinued and appropriate measures taken. Caution should be exercised when prescribing moxifloxacin to patients with a history of psychiatric disorders or current psychiatric illness.

Diarrhea associated with antibiotic use, including colitis

Cases of antibiotic-associated diarrhea (AAD) and antibiotic-associated colitis (AAC), including pseudomembranous colitis and Clostridium difficile-associated diarrhea, have been observed with the use of broad-spectrum antibiotics, including moxifloxacin. The severity of these events may range from mild diarrhea to fatal colitis. Therefore, it is important to consider this diagnosis in patients who develop severe diarrhea during or after moxifloxacin therapy. If suspected or confirmed AAD or AAC occurs, antimicrobial therapy, including moxifloxacin, should be discontinued immediately and appropriate therapeutic measures initiated. Additionally, appropriate infection control measures should be implemented to reduce the risk of transmission. Antiperistaltic agents are contraindicated in patients who develop severe diarrhea.

Patients with severe myasthenia

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

Tendon inflammation and tendon rupture

Tendon inflammation and ruptures (particularly, but not limited to, Achilles tendon), sometimes bilateral, may occur during therapy with quinolones and fluoroquinolones, developing even within 48 hours of starting treatment and possibly persisting for several months after discontinuation of therapy (see sections "Contraindications" and "Adverse reactions"). The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal impairment, solid organ transplant recipients, and patients receiving concomitant corticosteroid therapy. Therefore, concomitant use with corticosteroids should be avoided.

Moxifloxacin should be discontinued at the first signs of tendinitis (e.g., painful swelling or inflammation), 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.

Aortic aneurysm and aortic dissection, valvular regurgitation/insufficiency

Epidemiological studies suggest an increased risk of aortic aneurysm and aortic dissection, particularly in elderly patients, and development of aortic and mitral valve regurgitation following fluoroquinolone use. Rare cases of aortic aneurysm and aortic dissection, sometimes complicated by rupture (including fatal), as well as regurgitation/insufficiency of any heart valve, have been reported in patients receiving fluoroquinolones (see section "Adverse reactions"). Therefore, fluoroquinolones should be used only after careful benefit-risk assessment and consideration of alternative therapeutic options in patients with a history of aneurysm or congenital heart valve defect, or in patients with diagnosed aortic aneurysm and/or aortic dissection or heart valve disease, as well as in the presence of other risk factors or conditions predisposing to aortic aneurysm and aortic dissection, and valvular regurgitation/insufficiency (e.g., connective tissue disorders such as Marfan syndrome or vascular Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, arterial hypertension, rheumatoid arthritis), or also aortic aneurysm and dissection (e.g., vascular disorders such as Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren's syndrome), or also valvular regurgitation/insufficiency (e.g., infective endocarditis).

The risk of developing aortic aneurysm and aortic dissection, as well as their rupture, may be increased in patients receiving concomitant systemic corticosteroid therapy.

In case of sudden abdominal pain, chest pain, or back pain, patients should seek immediate medical attention.

Patients should be advised to seek immediate medical help if acute shortness of breath, rapid heartbeat, or development of abdominal or lower limb edema occurs.

Patients with renal impairment

Moxifloxacin should be used with caution in elderly patients with renal disorders who are unable to maintain adequate fluid volume, as dehydration increases the risk of renal failure.

Visual disturbances

In case of visual deterioration or any effect on the eyes, immediate consultation with an ophthalmologist is required (see sections "Ability to affect reaction rate when driving or operating machinery", "Adverse reactions").

Dysglycemia

As with all fluoroquinolones, cases of blood glucose deviations, both hypoglycemia and hyperglycemia, have been reported during moxifloxacin therapy (see section "Adverse reactions"). Dysglycemia occurred predominantly in elderly patients and diabetic patients receiving concomitant oral hypoglycemic agents (e.g., sulfonylureas) or insulin with moxifloxacin therapy. Cases of hypoglycemic coma have been reported. Diabetic patients are advised to closely monitor blood glucose levels.

Prevention of photosensitization reactions

Photosensitization reactions have been reported in patients receiving quinolones. However, study data indicate that the risk of photosensitization reactions with moxifloxacin is low. Nevertheless, patients should avoid prolonged and/or intense exposure to sunlight or ultraviolet radiation during moxifloxacin therapy (see section "Adverse reactions").

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with glucose-6-phosphate dehydrogenase deficiency, as well as those with a family history of this condition, are prone to hemolytic reactions during quinolone therapy. Therefore, moxifloxacin should be used with caution in this patient group.

Periarterial tissue inflammation

Moxifloxacin infusion solution is intended 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 soft tissue infections

The clinical efficacy of moxifloxacin in the treatment of severe infections related to burns, fasciitis, and infected diabetic foot associated with osteomyelitis has not been established.

Effect on biological tests

Moxifloxacin may affect the results of tests for Mycobacterium spp. by suppressing mycobacterial growth, which in turn may lead to false-negative results in patients receiving 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, appropriate antibacterial therapy should be initiated (see section "Pharmacodynamics").

Information on excipients

This medicinal product contains 787 mg (approximately 34 µmol) of sodium in one vial containing 250 mL of infusion solution, equivalent to 39.35% of the maximum daily sodium intake (2 g) recommended by WHO for adults.

Use during pregnancy or breastfeeding.

Pregnancy

The safety of moxifloxacin use during pregnancy in humans has not been established. Animal studies indicate reproductive toxicity (see section "Pharmacological properties"). The potential risk to humans has not been established. Due to the experimentally demonstrated risk of harmful effects of fluoroquinolones on weight-bearing cartilage in immature animals and considering the development of reversible joint lesions in children treated with certain fluoroquinolones, moxifloxacin should not be administered to pregnant women (see section "Contraindications").

Breastfeeding

There are no data on the use of moxifloxacin during breastfeeding in women. Preclinical studies indicate that a small amount of moxifloxacin passes into breast milk. Due to the lack of data on effects in breastfed infants and considering the experimental risk of harmful effects of fluoroquinolones on weight-bearing cartilage in immature animals, breastfeeding is contraindicated during moxifloxacin therapy (see section "Contraindications").

Fertility

Animal studies did not reveal any effect on fertility (see section "Pharmacological properties").

Ability to affect reaction rate when driving or operating machinery.

Studies on the effect of moxifloxacin on the ability to drive or operate machinery have not been conducted. However, fluoroquinolones, including moxifloxacin, may affect reaction rate when driving or operating machinery by causing central nervous system reactions (e.g., dizziness, acute transient visual loss) or acute and short-term loss of consciousness (syncope) (see section "Adverse reactions"). Patients are advised to assess their response to moxifloxacin before driving or operating machinery.

Dosage and Administration

Dosage

The recommended dosage regimen is 400 mg of moxifloxacin administered once daily as an infusion.

Initial intravenous therapy may be switched to oral administration of 400 mg moxifloxacin tablets when clinically indicated.

In clinical trials, most patients switched to oral moxifloxacin within 4 days (community-acquired pneumonia) or 6 days (complicated skin and soft 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 soft tissue infections.

Administration

The drug should be administered intravenously as a continuous infusion lasting at least 60 minutes (see also section "Special Instructions").

If clinically indicated, the infusion solution may be administered via a Y-site catheter together with compatible infusion solutions (see section "Special Precautions").

Renal/hepatic impairment

Patients with mild to severe renal impairment, as well as patients on chronic dialysis, such as those undergoing hemodialysis or continuous ambulatory peritoneal dialysis, do not require dose adjustment (see section "Pharmacological Properties" for further details).

There is insufficient information regarding the use of moxifloxacin 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 effects on cartilage in young animals (see section "Pharmacological Properties"), moxifloxacin is contraindicated in children and adolescents under 18 years of age (see section "Contraindications").

The efficacy and safety of moxifloxacin in pediatric patients and adolescents have not been established (see section "Contraindications").

Overdose.

No specific interventions are recommended following accidental overdose. In case of overdose, symptomatic treatment should be administered. Since QT interval prolongation may occur, ECG monitoring is required. Concomitant administration of activated charcoal with an oral or intravenous 400 mg dose of moxifloxacin reduces systemic bioavailability by more than 80% or 20%, respectively. Administration of activated charcoal at the early stage of absorption may effectively prevent excessive systemic exposure to moxifloxacin in cases of oral overdose.

Adverse reactions

The adverse reactions listed below were observed during clinical trials and the post-marketing period of moxifloxacin use at a dose of 400 mg once daily (intravenous therapy only, sequential [intravenous/oral], and oral). Adverse reactions are classified according to their frequency.

All adverse reactions, except nausea and diarrhea, occurred with a frequency of less than 3%.

Within each group, adverse events are listed in decreasing order of severity. Frequency is defined as follows: common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), infrequent (≥1/10,000, <1/1000), rare (<1/10,000), and not known (cannot be estimated based on available data).

* Rare cases of prolonged (lasting for months or years), disabling and potentially irreversible serious adverse reactions affecting various, sometimes multiple, organ systems and senses (including such reactions as tendon inflammation, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathy associated with paraesthesia and neuralgia, fatigue, psychiatric symptoms (including sleep disorders, anxiety, panic attacks, depression and suicidal thoughts), memory and concentration impairment, and disturbances of hearing, vision, taste and smell) have been reported in patients treated with quinolones and fluoroquinolones regardless of age and existing risk factors (see section "Special precautions for use").

** Rare cases of aortic aneurysm and aortic dissection, sometimes complicated by rupture (including fatal cases), as well as regurgitation/insufficiency of any heart valve have been reported in patients treated with fluoroquinolones (see section "Special precautions for use").

The frequency of the following effects is higher with intravenous administration of the drug followed by oral therapy or without such follow-up.

Common: increased gamma-glutamyl transferase levels.

Uncommon: ventricular tachyarrhythmia, hypotension, oedema, antibiotic-associated colitis (including pseudomembranous colitis, in rare cases associated with life-threatening complications, see section "Special precautions for use"), seizures (including grand mal seizures) (see section "Special precautions for use"), hallucinations, renal dysfunction (including increased blood urea nitrogen and creatinine levels), renal failure (see section "Special precautions for use").

Rarely, after treatment with other fluoroquinolones, adverse effects have been reported which are likely to possibly occur also during moxifloxacin treatment: increased intracranial pressure (including idiopathic intracranial hypertension), hypernatraemia, hypercalcaemia, haemolytic anaemia.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization of the medicinal product is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions.

Incompatibility.

The moxifloxacin infusion solution must not be administered simultaneously with other incompatible solutions, including: 10% sodium chloride solution; 20% sodium chloride solution; 4.2% sodium bicarbonate solution; 8.4% sodium bicarbonate solution.

This medicinal product should not be mixed with other medicinal products except those specified in the section "Special precautions for safety".

Shelf life.

5 years.

Storage conditions.

Keep out of the reach and sight of children.

Store in a dry, light-protected place at a temperature not below 15 °C.

Do not freeze.

The medicinal product should be stored in its original packaging.

Packaging.

250 ml of solution in a vial. 1 vial with package leaflet in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Bayer AG, Germany / Bayer AG, Germany

Manufacturer's address and place of business.

Kaiser-Wilhelm-Allee, 51368, Leverkusen, Germany / Kaiser-Wilhelm-Allee, 51368, Leverkusen, Germany.