Ultramox (Capsules) Instructions for Use

Marketing Authorization Holder

Atoll LLC (Russia)

Manufactured By

Ozon, LLC (Russia)

ATC Code

J01MA14 (Moxifloxacin)

Active Substance

Moxifloxacin (Rec.INN registered by WHO)

Dosage Form

Ultramox

Capsules 400 mg: 5, 7, 10, 14, 15, 20, 21, 28, 25, 30, 35, 40, 50, 60, 70, 80, 100, 120, or 200 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard gelatin, size No. 00, with a white opaque body and cap; the capsule contents are a mixture of powder and granules from white to light yellow or yellow; the granules are irregularly shaped, of different sizes, compaction of the capsule contents and shaping to the capsule form is allowed.

Excipients: microcrystalline cellulose – 56.2 mg, povidone K25 – 27.5 mg, croscarmellose sodium – 24 mg, magnesium stearate – 6 mg.

Capsule shell composition: body: titanium dioxide – 2%, gelatin – up to 100%; cap: titanium dioxide – 2%, gelatin – up to 100%.

5 pcs. – contour cell blisters (1) – cardboard packs.
5 pcs. – contour cell blisters (2) – cardboard packs.
5 pcs. – contour cell blisters (3) – cardboard packs.
5 pcs. – contour cell blisters (4) – cardboard packs.
5 pcs. – contour cell blisters (5) – cardboard packs.
5 pcs. – contour cell blisters (10) – cardboard packs.
7 pcs. – contour cell blisters (1) – cardboard packs.
7 pcs. – contour cell blisters (2) – cardboard packs.
7 pcs. – contour cell blisters (3) – cardboard packs.
7 pcs. – contour cell blisters (4) – cardboard packs.
7 pcs. – contour cell blisters (5) – cardboard packs.
7 pcs. – contour cell blisters (10) – cardboard packs.
10 pcs. – contour cell blisters (1) – cardboard packs.
10 pcs. – contour cell blisters (2) – cardboard packs.
10 pcs. – contour cell blisters (3) – cardboard packs.
10 pcs. – contour cell blisters (4) – cardboard packs.
10 pcs. – contour cell blisters (5) – cardboard packs.
10 pcs. – contour cell blisters (10) – cardboard packs.
20 pcs. – contour cell blisters (1) – cardboard packs.
20 pcs. – contour cell blisters (2) – cardboard packs.
20 pcs. – contour cell blisters (3) – cardboard packs.
20 pcs. – contour cell blisters (4) – cardboard packs.
20 pcs. – contour cell blisters (5) – cardboard packs.
20 pcs. – contour cell blisters (10) – cardboard packs.
10 pcs. – jars (1) – cardboard packs.
20 pcs. – jars (1) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
50 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
120 pcs. – jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

An antimicrobial agent from the fluoroquinolone group, it acts bactericidally. It exhibits activity against a wide range 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.

Based on in vitro studies, although the microorganisms listed below are susceptible to moxifloxacin, the safety and efficacy of its use in treating 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 topoisomerases 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 from the fluoroquinolone group. However, some gram-positive and anaerobic microorganisms resistant to other fluoroquinolones are susceptible to moxifloxacin.

Pharmacokinetics

After oral administration, Moxifloxacin is rapidly and almost completely absorbed. 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 the blood is reached within 0.5-4 hours and is 3.1 mg/L. After oral administration of moxifloxacin at a dose of 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 the tissues of the abdominal organs, peritoneal fluid, as well as in the tissues of the female genital organs.

Moxifloxacin undergoes phase II biotransformation and is excreted from the body by the kidneys and through the intestines, both unchanged and as inactive sulfocompounds (M1) and glucuronides (M2). Moxifloxacin is not biotransformed by the microsomal cytochrome P450 system. Metabolites M1 and M2 are present in the blood 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% through the intestines.

Indications

Infectious and inflammatory diseases caused by susceptible microorganisms: acute sinusitis; exacerbation of chronic bronchitis; community-acquired pneumonia (including that 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.

Take the capsule with a sufficient amount of water. Ingest the capsule at the same time each day to maintain consistent plasma concentrations.

You may take moxifloxacin with or without food. However, avoid concomitant intake with dairy products or mineral-fortified meals.

The standard treatment duration is 5 to 14 days. For specific infections, adhere to the following durations: acute bacterial sinusitis – 7 days; acute exacerbation of chronic bronchitis – 5 days; community-acquired pneumonia – 7 to 14 days; uncomplicated skin and skin structure infections – 7 days; complicated skin and skin structure infections, including diabetic foot infections – 7 to 21 days; complicated intra-abdominal infections – 5 to 14 days; uncomplicated pelvic inflammatory disease – 14 days.

Continue treatment for at least 48 to 72 hours after signs and symptoms have resolved or until evidence of bacterial eradication has been obtained. Do not exceed the total treatment duration of 21 days.

No dosage adjustment is required for patients with renal impairment, including those on hemodialysis or peritoneal dialysis. The use of moxifloxacin is contraindicated in patients with severe hepatic impairment (Child-Pugh C).

If a dose is missed, take it as soon as you remember. If it is almost time for the next dose, skip the missed dose. Do not take a double dose to make up for a forgotten one.

Do not chew or crush the capsules. Swallow the capsule whole.

Discontinue treatment immediately and contact your physician at the first sign of a skin rash, tendon pain or inflammation, or symptoms of peripheral neuropathy.

Adverse Reactions

Infections and infestations common – fungal superinfections.

Blood and lymphatic system disorders: uncommon – anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia, prolonged prothrombin time/increased INR; rare – change in thromboplastin concentration; very rare – increased prothrombin concentration/decreased INR.

Immune system disorders 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).

Metabolism and nutrition disorders uncommon – hyperlipidemia; rare – hyperglycemia, hyperuricemia; very rare – hypoglycemia.

Psychiatric disorders 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).

Nervous system disorders: 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, coordination disturbances (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.

Eye disorders uncommon – visual disturbances (especially with CNS reactions); very rare – transient loss of vision (especially with CNS reactions).

Ear and labyrinth disorders rare – tinnitus, hearing impairment, including deafness (usually reversible).

Cardiac disorders: 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).

Respiratory, thoracic and mediastinal disorders uncommon – dyspnea, asthmatic conditions.

Gastrointestinal disorders: common – nausea, vomiting, abdominal pain, diarrhea; uncommon – decreased appetite and reduced 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).

Hepatobiliary disorders: common – increased hepatic transaminase activity; uncommon – liver function disorders (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).

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

Musculoskeletal and connective tissue disorders: 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.

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

General disorders and administration site conditions common – injection/infusion site reactions.

General disorders and administration site conditions 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, renal function impairment, 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 the electrophysiological parameters of the heart 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 elevations 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 levels; 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 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 for the treatment of patients with pelvic inflammatory diseases, except in cases where the presence of fluoroquinolone-resistant N. gonorrhoeae is excluded. If it is not possible to exclude 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 (e.g., a cephalosporin) should be considered.

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

Effect on ability to drive and operate machinery

Fluoroquinolones, including Moxifloxacin, may impair the ability of patients 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 concomitant 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, diphemanil).

With simultaneous oral intake of antacids, multivitamins and minerals, impaired absorption of moxifloxacin is possible 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 (e.g., 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 anticoagulants 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.