Moflox^® 400 (Tablets) Instructions for Use

Marketing Authorization Holder

Hetero Labs, Limited (India)

Manufactured By

Makiz-Pharma, LLC (Russia)

ATC Code

J01MA14 (Moxifloxacin)

Active Substance

Moxifloxacin (Rec.INN registered by WHO)

Dosage Forms

	Moflox® 400	Film-coated tablets, 400 mg: 5, 7, 10, 14 or 20 pcs
		Film-coated tablets, 400 mg: 5, 7, 10, 14 or 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets pink, capsule-shaped, biconvex, engraved with “80” on one side and “I” on the other; on cross-section, the core is from light yellow to yellow.

Excipients: microcrystalline cellulose 101 – 150.2 mg, microcrystalline cellulose 102 – 96 mg, croscarmellose sodium – 40 mg, colloidal silicon dioxide – 6 mg, povidone K30 (kollidon 30) – 12 mg, magnesium stearate – 9 mg.

Shell composition Opadry pink 03B34285 -15 mg (hypromellose HPMC 2910 (E464) – 62.5%, titanium dioxide (E171) – 28.73%, macrogol (PEG 400) – 6.25%, iron oxide red dye (E172) – 2.5%, iron oxide yellow dye (E172) – 0.02%).

5 pcs. – Al/Al blisters (1) – cardboard packs.
5 pcs. – Al/Al blisters (2) – cardboard packs.
7 pcs. – Al/Al blisters (1) – cardboard packs.
7 pcs. – Al/Al blisters (2) – cardboard packs.
10 pcs. – Al/Al blisters (1) – cardboard packs.
10 pcs. – Al/Al blisters (2) – cardboard packs.

Film-coated tablets pink, capsule-shaped, biconvex, engraved with “80” on one side and “I” on the other; on cross-section, the core is from light yellow to yellow.

Excipients: microcrystalline cellulose 101 – 150.2 mg, microcrystalline cellulose 102 – 96 mg, croscarmellose sodium – 40 mg, colloidal silicon dioxide – 6 mg, povidone K30 (kollidon 30) – 12 mg, magnesium stearate – 9 mg.

Shell composition Opadry pink 03B34285 -15 mg (hypromellose HPMC 2910 (E464) – 62.5%, titanium dioxide (E171) – 28.73%, macrogol (PEG 400) – 6.25%, iron oxide red dye (E172) – 2.5%, iron oxide yellow dye (E172) – 0.02%).

5 pcs. – contour cell packs (1) – cardboard packs.
5 pcs. – contour cell packs (2) – cardboard packs.
7 pcs. – contour cell packs (1) – cardboard packs.
7 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Systemic antibacterial agents; quinolone derivatives; fluoroquinolones

Pharmacological Action

An antimicrobial agent from the fluoroquinolone group, it acts bactericidally. It demonstrates activity against a wide spectrum of gram-positive and gram-negative microorganisms, anaerobic, acid-fast and atypical bacteria: Mycoplasma spp., Chlamydia spp., Legionella spp. It is effective against bacterial strains resistant to beta-lactams and macrolides.

It is active against most strains of microorganisms: gram-positive – Staphylococcus aureus (including strains not susceptible to methicillin), Streptococcus pneumoniae (including strains resistant to penicillin and macrolides), Streptococcus pyogenes (group A); gram-negative – Haemophilus influenzae (including both beta-lactamase-producing and non-producing strains), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including both beta-lactamase-producing and non-producing strains), Escherichia coli, Enterobacter cloacae; atypical – Chlamydia pneumoniae, Mycoplasma pneumoniae.

According to in vitro studies, although the microorganisms listed below are sensitive to moxifloxacin, the safety and efficacy of its use in the treatment of infections have not been established. Gram-positive microorganisms: Streptococcus milleri, Streptococcus mitior, Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus cohnii, Staphylococcus epidermidis (including strains susceptible to methicillin), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Corynebacterium diphtheriae. Gram-negative microorganisms: Bordetella pertussis, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter intermedius, Enterobacter sakazaki, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii. Anaerobic microorganisms: Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides uniformis, Fusobacterium spp., Porphyromonas spp., Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus, Prevotella spp., Propionibacterium spp., Clostridium perfringens, Clostridium ramosum. Atypical microorganisms: Legionella pneumophila, Coxiella burnetii.

It blocks topoisomerase II and IV, enzymes that control the topological properties of DNA and are involved in DNA replication, repair, and transcription. The action of moxifloxacin depends on its concentration in the blood and tissues. The minimum bactericidal concentrations are almost identical to the minimum inhibitory concentrations.

Resistance development mechanisms that inactivate penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines do not affect the antibacterial activity of moxifloxacin. There is no cross-resistance between moxifloxacin and these drugs. A plasmid-mediated resistance development mechanism was not observed. The overall frequency of resistance development is low. In vitro studies have shown that resistance to moxifloxacin develops slowly as a result of a series of sequential mutations. When microorganisms are repeatedly exposed to moxifloxacin at sub-minimum inhibitory concentrations, the MIC values increase only slightly. Cross-resistance is observed between drugs of the fluoroquinolone group. However, some gram-positive and anaerobic microorganisms resistant to other fluoroquinolones are susceptible to moxifloxacin.

Pharmacokinetics

After oral administration, Moxifloxacin is absorbed rapidly and almost completely. The absolute bioavailability is about 91%. The pharmacokinetics of moxifloxacin when taken in doses from 50 to 1200 mg as a single dose, as well as 600 mg/day for 10 days, are linear. After a single oral dose of moxifloxacin 400 mg, C_max in blood is reached within 0.5-4 hours and is 3.1 mg/L. After oral administration of moxifloxacin 400 mg once daily, C_ss^max and C_ss^min are 3.2 mg/L and 0.6 mg/L, respectively.

Binding to blood proteins (mainly albumin) is about 45%. Moxifloxacin is rapidly distributed in organs and tissues. V_d is approximately 2 L/kg. High concentrations of moxifloxacin, exceeding those in plasma, are achieved in lung tissue (including epithelial lining fluid, alveolar macrophages), in the sinuses (maxillary and ethmoid sinuses), in nasal polyps, and in inflammatory foci (in blister fluid in skin lesions). In interstitial fluid and saliva, Moxifloxacin is found in a free, unbound form, at concentrations higher than in plasma. Furthermore, high concentrations of moxifloxacin are found in tissues of the abdominal organs, peritoneal fluid, as well as in tissues of the female genital organs.

Moxifloxacin undergoes phase II biotransformation and is excreted from the body by the kidneys, as well as through the intestines, both unchanged and in the form of inactive sulfocompounds (M1) and glucuronides (M2). Moxifloxacin is not metabolized by the microsomal cytochrome P450 system. Metabolites M1 and M2 are present in plasma at concentrations lower than the parent compound. Preclinical studies have proven that these metabolites have no negative impact on the body in terms of safety and tolerability.

T_1/2 is approximately 12 hours. The mean total clearance after a single oral dose of moxifloxacin 400 mg is 179-246 ml/min. Renal clearance is 24-53 ml/min. This indicates partial tubular reabsorption of moxifloxacin. About 22% of a single dose (400 mg) is excreted unchanged by the kidneys, about 26% is excreted through the intestines.

Indications

Infectious and inflammatory diseases caused by susceptible microorganisms: acute sinusitis; exacerbation of chronic bronchitis; community-acquired pneumonia (including caused by strains of microorganisms with multiple antibiotic resistance); uncomplicated skin and soft tissue infections; complicated skin and subcutaneous structure infections (including infected diabetic foot); complicated intra-abdominal infections, including polymicrobial infections, e.g., intraperitoneal abscesses; uncomplicated inflammatory diseases of the pelvic organs (including salpingitis and endometritis).

It is necessary to take into account the current official guidelines on the rules for the use of antibacterial agents.

ICD codes

Dosage Regimen

Administer orally at a dose of 400 mg once daily.

The tablet can be taken with or without food. Swallow the tablet whole with a sufficient amount of liquid.

The standard treatment duration is 5 to 10 days for most indications, such as acute bacterial exacerbation of chronic bronchitis, acute sinusitis, and uncomplicated skin and skin structure infections.

For community-acquired pneumonia, administer for 7 to 14 days.

For complicated skin and skin structure infections, including diabetic foot infections, the treatment course is typically 7 to 21 days.

For complicated intra-abdominal infections, the duration of therapy is usually 5 to 14 days.

For uncomplicated pelvic inflammatory disease, the recommended treatment duration is 14 days.

Do not exceed the maximum daily dose of 400 mg.

The total duration of therapy is determined by the severity of the infection, the causative pathogen, and the patient’s clinical response.

Continue treatment for at least 2 to 3 days after the signs and symptoms of infection have resolved.

In elderly patients, no dosage adjustment is required based on age alone.

No dosage adjustment is required for patients with any degree of renal impairment, including those on hemodialysis or peritoneal dialysis.

Contraindicated in patients with severe hepatic impairment (Child-Pugh C). No dosage adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh A and B).

Adverse Reactions

Infectious diseases common – fungal superinfections.

From the hematopoietic system: uncommon – anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia, prolonged prothrombin time/increased INR; rare – change in thromboplastin concentration; very rare – increased prothrombin concentration/decreased INR.

From the immune system uncommon – allergic reactions, urticaria, pruritus, rash, eosinophilia; rare – anaphylactic/anaphylactoid reactions, angioedema, including laryngeal edema (potentially life-threatening); very rare – anaphylactic/anaphylactoid shock (including potentially life-threatening).

From metabolism uncommon – hyperlipidemia; rare – hyperglycemia, hyperuricemia; very rare – hypoglycemia.

From the psyche uncommon – anxiety, psychomotor hyperactivity, agitation; rare – emotional lability, depression, hallucinations; very rare – depersonalization, psychotic reactions (potentially manifesting in behavior with a tendency to self-harm, such as suicidal thoughts or suicide attempts).

From the nervous system: common – dizziness, headache; uncommon – paresthesia, dysesthesia, taste disturbances (including in very rare cases ageusia), confusion, disorientation, sleep disorders, tremor, vertigo, somnolence; rare – hypoesthesia, smell disturbances (including anosmia), atypical dreams, impaired coordination (including gait disturbances due to dizziness or vertigo, in very rare cases leading to injuries from falls, especially in elderly patients), seizures with various clinical manifestations (including grand mal seizures), attention disturbances, speech disturbances, amnesia, peripheral neuropathy, polyneuropathy; very rare – hyperesthesia.

From the organ of vision uncommon – visual disturbances (especially with CNS reactions); very rare – transient loss of vision (especially with CNS reactions).

From the organ of hearing rare – tinnitus, hearing impairment, including deafness (usually reversible).

From the cardiovascular system: common – QT interval prolongation in patients with concomitant hypokalemia; uncommon – QT interval prolongation, palpitations, tachycardia, vasodilation; rare – increased blood pressure, decreased blood pressure, syncope, ventricular tachyarrhythmias; very rare – nonspecific arrhythmias, polymorphic ventricular tachycardia (torsades de pointes), cardiac arrest (primarily in persons with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia).

From the respiratory system uncommon – dyspnea, asthmatic condition.

From the digestive system: common – nausea, vomiting, abdominal pain, diarrhea; uncommon – decreased appetite and decreased food intake, constipation, dyspepsia, flatulence, gastroenteritis (except erosive gastroenteritis), increased amylase activity; rare – dysphagia, stomatitis, pseudomembranous colitis (in very rare cases associated with life-threatening complications).

From the liver and biliary tract: common – increased activity of liver transaminases; uncommon – impaired liver function (including increased LDH activity), increased bilirubin concentration, increased GGT and ALP activity; rare – jaundice, hepatitis (predominantly cholestatic); very rare – fulminant hepatitis, potentially leading to life-threatening liver failure (including fatal cases).

From the skin and subcutaneous tissues very rare – bullous skin reactions, e.g., Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening).

From the musculoskeletal system: uncommon – arthralgia, myalgia; rare – tendinitis, increased muscle tone and cramps, muscle weakness; very rare – arthritis, tendon ruptures, gait disturbance due to musculoskeletal damage, exacerbation of myasthenia gravis symptoms.

From the urinary system uncommon – dehydration (caused by diarrhea or reduced fluid intake); rare – impaired renal function, renal failure due to dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing renal impairment.

Local reactions common – injection/infusion site reactions.

General reactions uncommon – general malaise, nonspecific pain, sweating.

The frequency of the following adverse reactions was higher in the group receiving step-down therapy: common – increased GGT activity; uncommon – ventricular tachyarrhythmias, arterial hypotension, edema, pseudomembranous colitis (in very rare cases associated with life-threatening complications), seizures with various clinical manifestations (including grand mal seizures), hallucinations, impaired renal function, renal failure (due to dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing renal impairment).

Contraindications

Hypersensitivity to moxifloxacin, other quinolones; history of tendon pathology developed due to treatment with quinolone antibiotics; in preclinical and clinical studies, after administration of moxifloxacin, changes in cardiac electrophysiological parameters were observed, expressed as QT interval prolongation. In this regard, the use of moxifloxacin is contraindicated in patients of the following categories: congenital or documented acquired QT interval prolongation, electrolyte disturbances, especially uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; history of symptomatic arrhythmias; Moxifloxacin should not be used with other drugs that prolong the QT interval; due to limited clinical data, the use of moxifloxacin is contraindicated in patients with impaired liver function (Child-Pugh class C) and in patients with transaminase levels more than 5 times the upper limit of normal; pregnancy, breastfeeding; children and adolescents under 18 years of age.

Use with caution in diseases of the CNS (including diseases suspected of involving the CNS) predisposing to the occurrence of seizures and lowering the seizure threshold; in patients with a history of psychoses and/or psychiatric diseases; in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia and cardiac arrest, especially in women and elderly patients; in myasthenia gravis; in liver cirrhosis; with simultaneous use of drugs that reduce potassium content; in patients with a genetic predisposition or actual deficiency of glucose-6-phosphate dehydrogenase.

Use in Pregnancy and Lactation

The use of moxifloxacin during pregnancy and breastfeeding is contraindicated.

Use in Hepatic Impairment

The use of moxifloxacin is contraindicated in patients with impaired liver function (Child-Pugh class C) and in patients with transaminase elevations more than 5 times the upper limit of normal. Use with caution in liver cirrhosis.

Use in Renal Impairment

No dosage regimen adjustment is required for patients with impaired renal function (including with CrCl <30 ml/min/1.73 m²), as well as for patients on continuous hemodialysis and long-term ambulatory peritoneal dialysis.

Pediatric Use

Use in children and adolescents under 18 years of age is contraindicated.

Geriatric Use

Use with caution in elderly patients to avoid worsening of concomitant diseases.

Special Precautions

In some cases, hypersensitivity and allergic reactions may develop after the first use of moxifloxacin, about which a doctor should be informed immediately. Very rarely, even after the first use, anaphylactic reactions may progress to life-threatening anaphylactic shock. In these cases, treatment with moxifloxacin should be discontinued and necessary therapeutic measures (including anti-shock) should be started immediately.

Use with caution in women and elderly patients. Since women have a longer QT interval compared to men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients are also more susceptible to the effects of drugs that affect the QT interval.

The degree of QT interval prolongation may increase with increasing moxifloxacin concentration, so the recommended dose should not be exceeded. QT interval prolongation is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia.

The patient should be informed that in case of symptoms of liver failure, symptoms of skin or mucous membrane lesions, symptoms of neuropathy (pain, burning, tingling, numbness, or weakness), it is necessary to consult a doctor before continuing treatment with moxifloxacin.

The use of broad-spectrum antibacterial drugs, including Moxifloxacin, is associated with the risk of developing pseudomembranous colitis. Drugs that inhibit intestinal peristalsis are contraindicated in the development of severe diarrhea.

During therapy with quinolones, including moxifloxacin, the development of tendonitis and tendon rupture is possible, especially in the elderly and patients receiving corticosteroids. Cases that occurred within several months after completion of treatment have been described. At the first symptoms of pain or inflammation at the site of injury, the use of moxifloxacin should be discontinued and the affected limb should be rested.

During treatment, exposure to direct sunlight and UV radiation should be avoided.

Moxifloxacin is not recommended for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains. In the case of suspected or confirmed infections caused by MRSA, treatment with appropriate antibacterial drugs should be prescribed.

The ability of moxifloxacin to suppress the growth of mycobacteria may cause in vitro interaction of moxifloxacin with the test for Mycobacterium spp., leading to false-negative results when analyzing samples from patients receiving Moxifloxacin.

Psychiatric reactions may occur even after the first prescription of fluoroquinolones, including Moxifloxacin. In very rare cases, depression or psychotic reactions progress to the emergence of suicidal thoughts and behavior with a tendency to self-harm, including suicide attempts. If such reactions occur in patients, Moxifloxacin should be discontinued and necessary measures taken. Caution should be exercised when using moxifloxacin in patients with a history of psychoses and/or psychiatric diseases.

Due to the widespread and increasing incidence of infections caused by fluoroquinolone-resistant Neisseria gonorrhoeae, monotherapy with moxifloxacin should not be used in the treatment of patients with pelvic inflammatory diseases, except in cases where the presence of fluoroquinolone-resistant N. gonorrhoeae has been ruled out. If it is not possible to rule out the presence of fluoroquinolone-resistant N. gonorrhoeae, the issue of supplementing empirical therapy with moxifloxacin with an appropriate antibiotic that is active against N. gonorrhoeae (for example, a cephalosporin) should be considered.

During therapy with moxifloxacin, dysglycemia occurred mainly in elderly diabetic patients receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylurea drugs) or insulin. When treating patients with diabetes, careful monitoring of blood glucose concentration is recommended.

Effect on ability to drive vehicles and operate machinery

Fluoroquinolones, including Moxifloxacin, may impair patients’ ability to drive a car and engage in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions due to the effect on the CNS and visual impairment.

Drug Interactions

The possible additive effect of QT interval prolongation by moxifloxacin and other drugs that affect QT interval prolongation should be taken into account. Due to the combined use of moxifloxacin and drugs affecting QT interval prolongation, the risk of developing ventricular arrhythmia, including polymorphic ventricular tachycardia of the ‘torsades de pointes’ type, increases. The combined use of moxifloxacin with the following drugs affecting QT interval prolongation is contraindicated: class IA antiarrhythmic drugs (including quinidine, hydroquinidine, disopyramide); class III antiarrhythmic drugs (including amiodarone, sotalol, dofetilide, ibutilide); antipsychotics (including phenothiazine, pimozide, sertindole, haloperidol, sultopride); tricyclic antidepressants; antimicrobial drugs (sparfloxacin, intravenous erythromycin, pentamidine, antimalarial drugs, especially halofantrine); antihistamines (terfenadine, astemizole, mizolastine); others (cisapride, intravenous vincamine, bepridil, difemanil).

With simultaneous oral intake of antacids, multivitamins and minerals, absorption of moxifloxacin may be impaired due to the formation of chelate complexes with polyvalent cations contained in these drugs. As a result, the plasma concentration of moxifloxacin may be significantly lower than therapeutic. In this regard, antacids, antiretroviral drugs (for example, didanosine) and other drugs containing magnesium, aluminum, sucralfate, iron, zinc should be taken at least 4 hours before or 4 hours after oral intake of moxifloxacin.

In patients receiving anticoagulants in combination with antibiotics, including moxifloxacin, cases of increased anticoagulant activity of anticoagulant drugs have been noted. Risk factors are the presence of an infectious disease (and the accompanying inflammatory process), age and the general condition of the patient. Although no interaction between moxifloxacin and warfarin has been identified, in patients receiving combined treatment with these drugs, INR should be monitored and the dose of indirect anticoagulants should be adjusted if necessary.

Moxifloxacin and digoxin do not have a significant effect on each other’s pharmacokinetic parameters. With repeated administration of moxifloxacin, the C_max of digoxin increased by approximately 30%. However, the AUC and C_min values of digoxin do not change.

With simultaneous oral use of activated charcoal and moxifloxacin at a dose of 400 mg, the systemic bioavailability of moxifloxacin decreases by more than 80% due to slowed absorption. In case of overdose, the use of activated charcoal at an early stage of absorption prevents a further increase in systemic exposure.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.