MOXICUM

 

TRADE NAME

Moxicum

 

INTERNATIONAL NONPROPRIETARY NAME

Moxifloxacin

 

CHEMICAL NAME

1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-yl]-4-oxo-3-quinoline carboxylic acid (in the hydrochloride form)

 

PHARMACEUTICAL FORM

Solution for infusion

Description: A greenish-yellow clear solution practically free from particles.

 

COMPOSITION

250 ml of solution for infusion contain

Active ingredient: moxifloxacin (as moxifloxacin hydrochloride) 400 mg.

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

 

ATC CODE      J01MA14

 

PHARMACOTHERAPEUTIC GROUP

Fluoroquinolone antibacterials.

 

PHARMACOLOGICAL PROPERTIES

PHARMACODYNAMICS

Moxicum represents a broad-spectrum bactericidal antibacterial fluoroquinolone agent. It inhibits topoisomerase II (DNA-gyrase) and topoisomerase IV-enzymes, required for bacterial DNA replication, transcription, reparation and recombination. The inhibited isomerase function leads to irreversible changes in the bacterial cells and to their death. Minimum bactericidal concentrations almost do not differ from the minimum inhibitory concentrations. It exhibits no cross-resistance to penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines. Overall frequency of resistance development is low. Resistance to moxifloxacin develops slowly and results from a series of consecutive mutations. A cross-resistance is observed between the fluoroquinolones, however some gram-positive and anaerobic microorganisms resistant to other fluoroquinolones are susceptible to moxifloxacin.

Moxifloxacin exhibits activity against a wide range of gram-negative and gram-positive microorganisms, anaerobic, acid-resistant and atypical bacteria: Mycoplasma spp., Chlamydia spp., Legionella spp., and is effective against bacterial strains resistant to beta-lactam antibiotics and macrolides.

Moxifloxacin spectrum of antibacterial activity includes the following microorganisms: gram-positive microorganisms - Streptococcus pneumoniae (including penicillin-resistant strains and strains with multiple antibiotic resistance)*, Streptococcus pyogenes (group А)*, Streptococcus milleri, Streptococcus mitis, Streptococcus agalactiae*, Streptococcus dysgalactiae, Streptococcus anginosus*, Streptococcus constellatus*, Staphylococcus aureus (including methicillin-resistant strains)*, Staphylococcus cohnii, Staphylococcus epidermidis (including methicillin-resistant strains), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Corynebacterium diphtheria, Enterococcus faecalis (only strains susceptible to vancomycin and gentamicin)*; gram-negative microorganisms - Haemophillus influenzae (including beta-lactamase-producing and -nonproducing strains)*, Haemophillus parainfluenzae*, Klebsiella pneumoniae*, Moraxella catarrhalis (including beta-lactamase-producing and -nonproducing strains)*, Escherichia coli*, Enterobacter cloacae*, 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 thetaiotaomicron*, Bacteroides uniformis, Fusobacterium spp., Peptostreptococcus spp.*, Porphyromonas spp., Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus, Prevotella spp., Propionibacterium spp., Clostridium perfringens*, Clostridium ramosum; abnormal microorganisms - Chlamydia pneumoniae*, Mycoplasma pneumoniae*, Legionella pneumophila*, Coxiella burnetti.

Moxifloxacin is less active against Staphylococcus aureus (methicillin-/ ofloxacin-resistant strains)*, Staphylococcus epidermidis (methicillin-/ ofloxacin-resistant strains)*, Pseudomonas aeruginosa, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia.

* The susceptibility to moxifloxacin is confirmed by clinical data.

PHARMACOKINETICS

Absorption

After a single one-hour infusion at a dose of 400 mg, the peak concentration is achieved at the end of the infusion and amounts to about 4.1 mg/L, that corresponds to its increase by approximately 26% as compared with the value of this parameter following oral administration. After multiple intravenous one-hour infusions of Moxicum at a dose of 400 mg, the peak and minimum steady-state plasma concentrations range from 4.1 to 5.9 mg/L and from 0.43 to 0.84 mg/L, respectively.

Distribution

Moxifloxacin is very rapidly distributed in the extravascular bed. The volume of distribution amounts to 1.7 – 2.7 L/kg. The serum protein binding (mostly with albumins) amounts to about 30 - 50% and doesn’t depend on the substance concentration.

High concentrations of the medication, exceeding the same in the plasma, originate in the pulmonary tissue (including alveolar macrophages), bronchial and paranasal sinus mucous membranes, in the exudate from the skin inflammation site. A high concentration of the medication in a free state is observed in saliva and interstitial fluid. Moreover, high concentrations of the medication are found in the abdominal cavity organs and peritoneal fluid as well as in the female genital organs.

Metabolism

Following the 2^-nd biotransformation phase, moxifloxacin is excreted renally and via the gastrointestinal tract, both unchanged and as inactive sulfocompounds (M1) and glucuronides (M2). Moxifloxacin doesn’t undergo biotransformation by cytochrome P450 microsomal system.

Elimination

The elimination half-life is about 12 hours. Approximately 45% of moxifloxacin is eliminated in unchanged form (about 20% of them is excreted in urine and about 25% - in faeces). Apparent total body clearance is 12 ± 2.0 L/h and renal clearance is 2.6 ± 0.5 L/h.

 

THERAPEUTIC INDICATIONS

- acute sinusitis;

- acute exacerbation of chronic bronchitis;

- community-acquired pneumonia;

- complicated and uncomplicated skin and soft tissues infections (including diabetic foot infection);

- complicated intra-abdominal infections, including polymicrobial infections (such as abscess formation);

- uncomplicated inflammatory pelvic diseases (including salpingitis and endometritis).

 

DOSAGE AND ADMINISTRATION

The medicine is administered intravenously by infusion. The recommended dose is 400 mg once a day.

The treatment duration is determined according to the severity of infection or clinical effect.

Treatment duration:

- in case of acute sinusitis - 7 days;

- in case of acute exacerbations of chronic bronchitis - 5 days;

- in case of community-acquired pneumonia the total duration of   step-down therapy (intravenous injection with subsequent oral administration) makes 7-14 days;

- in case of uncomplicated skin and soft tissues infections – 7 days;

- in case of complicated skin and soft tissues infections the treatment duration (intravenous injection with subsequent oral administration) makes 7-21 days;

- in case of complicated intra-abdominal infections, including polymicrobial infections the treatment duration (intravenous injection with subsequent oral administration) makes 5-14 days;

- in case of uncomplicated inflammatory pelvic diseases (including salpingitis and endometritis) the treatment duration makes 14 days.

 

The dosing adjustment is not required for elderly patients, patients with insignificant compromised liver and kidney function (including creatinine clearance ≤ 30 ml/min/1.73 m²), as well as for patients receiving continuous hemodialysis and continuous ambulatory peritoneal dialysis.

Rules for administration of solution for infusion

The drug is injected as an intravenous infusion over at least 60 minutes. The solution for infusion can be given directly or through the T-shaped catheter.

Moxicum solution for infusion prepared with the use of the below listed solutions for infusion remains stable over 24 hours at room temperature. The following solutions can be considered as compatible with Moxicum: water for injections, 0.9% sodium chloride solution, 1М solution of sodium chloride, 5% dextrose (glucose) solution, 10% dextrose (glucose) solution, 40% dextrose (glucose) solution, 20% xylite solution, Ringer's solution, lactated Ringer's solution. 

If Moxicum solution for infusion is applied together with another drug, each drug should be injected separately.

The drug must not be frozen or refrigerated, as upon cooling a precipitate can form that dissolves at room temperature. Only clear solution should be injected.

 

CONTRAINDICATIONS

- hypersensitivity to the drug components;

- pregnancy;

- lactation (breast feeding);

- children and adolescents under 18 years old.

 

ADVERSE EFFECTS

Moxicum is usually well tolerated; most adverse effects are rare or moderate.

Digestive system: common: abdominal pain, dyspepsia (including flatulence, nausea, vomiting, constipation, diarrhoea), increase in liver transaminases activity; rare: mouth dryness, oral moniliasis, anorexia, stomatitis, glossitis, increase in gamma-glutamyl transferase level.

Nervous system: common: dizziness, headache; rare: asthenia, insomnia or somnolence, nervousness, feeling of anxiety, tremor, paresthesias.

Sense organs: common: taste alterations.

Cardiovascular system: rare: tachycardia, increase of blood pressure, palpitation, chest pain, prolonged QT interval.

Respiratory system: rare: dyspnea; very rarely – bronchial asthma.

Musculoskeletal apparatus: rarely - arthralgia, myalgia.

Urogenital system: rarely – vaginal candidiasis, vaginitis.

Allergic reactions: rarely - rash, itching.

Laboratory tests: rarely - leucopenia, prothrombin time increase, eosinophilia, thrombocitosis, amylase activity increase.

Other: rarely - moniliasis, general discomfort, hyperhydrosis.

 

SPECIAL INDICATIONS

Moxicum should be prescribed with caution in patients with epileptic syndrome (including in past medical history), epilepsy, severe liver dysfunction, prolonged QT interval syndrome, and in patients with conditions predisposing to arrhythmias, such as bradycardia and acute myocardial ischemia.

In case severe diarrhea develops during the treatment, the drug administration should be discontinued.

No reactions of photosensitivity were observed upon practical administration of moxifloxacin. Nevertheless, patients receiving moxifloxacin should avoid direct sunlight and UV-irradiation.

 

INFLUENCE ON ABILITY FOR DRIVING AND OPERATING MECHANISMS 

The drug may cause adverse reactions of the central nervous system, thus the ability for driving and operating other mechanisms is determined on the basis of the patient`s reaction evaluation to the drug.

 

PREGNANCY AND LACTATION

The safety of the drug administration in pregnancy has not been established; therefore its administration is contraindicated.

Small amount of moxifloxacin secretes into breast milk, thus breastfeeding should be discontinued if it is necessary to prescribe the drug in the period of lactation.

 

PEDIATRIC USE

The effectiveness and safety in children and teenagers under 18 has not been established.

 

DRUG INTERACTION

No dose correction is needed in concomitant use with atenolol, warfarin, ranitidine, calcium-containing additives, theophylline, oral contraceptives, glibenclamide, itraconazole, digostin, morphine, probenecid (absence of clinically relevant interaction with moxifloxacin is confirmed).

Administration of moxifloxacin with antiarrhythmic drugs of class I A (chinidin, procainamide) or class III (amiodarone, sotalol), as well as with the drugs prolonging QT interval (cisapride, erythromycin, antipsychotic drugs, tricyclic antidepressants), can lead to additive affect in relation to QT interval prolongation.

Concomitant use with corticosteroids increases a risk of tendovaginitis or tendon rupture.

Moxicum solution for infusion is incompatible with 10% and 20% sodium chloride solutions and 4.2% and 8.4% sodium hydrocarbonate solutions.

 

OVERDOSE

Administration of moxifloxacin in single doses of up to 1200 mg and in repeated doses of 600 mg over 10 days was not associated with any adverse effects.

Treatment: in case of overdose the treatment depends on the clinical picture and symptomatic supportive treatment with ECG monitoring should be performed. Administration of activated charcoal in case of overdose has a very limited significance.

 

PACKAGING

Solution for intravenous infusion in a 250 ml colorless glass vial with a bromobutyl rubber stopper and a combined aluminium flip off cap.

One vial in a carton box with an enclosed leaflet.

 

STORAGE CONDITIONS

Store at temperature not exceeding 25°С.

Keep out of reach of children!

 

SHELF LIFE

3 years from the date of manufacture.

Do not apply after the expiry date.

 

SALES TERMS

Sold under prescription.

 

MANUFACTURER

The holder of Marketing Authorization is

“DR SERTUS İLAÇ SANAYİ VE TİCARET LİMİTED ŞİRKETİ”, TURKEY.

 

Manufactured by

“Mefar İlaç Sanayii A.Ş.”, Turkey

(Ramazanoğlu Mah. Ensar Cad. No: 20, 34906 Kurtköy-Pendik/İstanbul).