Moflaxia, 400 mg 7 pcs
€14.41 €12.01
Pharmacology
Pharmacodynamics
Mechanism of action
Inhibits topoisomerase II (DNA-gyrase) and topoisomerase IV – enzymes necessary for replication, transcription, repair and recombination of bacterial DNA. It disrupts DNA synthesis of the microbial cell and has a bactericidal effect.
The mechanism of action of fluoroquinolones including moxifloxacin is different from that of macrolides, beta-lactams, aminoglycosides or tetracyclines, so microorganisms resistant to these classes of drugs may be sensitive to moxifloxacin. Resistance to fluoroquinolones is primarily due to mutation of topoisomerase II (DNA-gyrase) or topoisomerase IV genes, reduced outer membrane permeability or efflux. Resistance to moxifloxacin in vitro develops slowly and is associated with multistep mutations. Resistance to moxifloxacin in vitro in Gram-positive bacteria occurs with a frequency of 1.8-10-9 to 1-10-11 or less.
Cross-resistance
Cross-resistance between moxifloxacin and other fluoroquinolones has been observed in Gram-negative bacteria. Gram-positive bacteria resistant to other fluoroquinolones may be sensitive to moxifloxacin. Cross-resistance between moxifloxacin and other classes of antimicrobial agents is unknown.
Moxifloxacin is active (both in vitro and by the results of clinical studies on the treatment of several infections) against most strains of the following microorganisms: Aerobic Gram-positive microorganisms – Enterococcus faecalis, Staphylococcus aureus, Streptococcus anginosus, Streptococcus constellatus, Streptococcus pneumoniae (including multi-resistant strains [MDRSP]*), Streptococcus pyogenes; aerobic gram-negative microorganisms – Enterobacter cloacae, Esherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis, Yersinia pestis; anaerobic microorganisms – Bacteroides fragilis, Bacteroides thetaiotaomicron, Clostridium perfringens, Peptostreptococcus spp., as well as other microorganisms – Chlamydia pneumoniae, Mycoplasma pneumoniae.
* Strains with multiple resistance to antibiotics (Multi-drug resistant Streptococcus pneumoniae, MDRSP), including strains formerly known as PRSP (Penicillin-resistant S. pneumoniae) and strains resistant to two or more of the following antibiotics: penicillin (at MPC ≥2 µg/mL), second-generation cephalosporins (e.g. cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole.
According to in vitro studies, moxifloxacin is active (MPC ≤2 µg/mL) against most (over 90%) strains of the following microorganisms: aerobic gram-positive microorganisms – Staphylococcus epidermidis, Streptococcus agalactiae, Streptococcus viridans; aerobic gram-negative microorganisms – Citrobacter freundii, Klebsiella oxytoca, Legionella pneumophyla; anaerobic microorganisms – Fusobacterium spp., Prevotella spp. Clinical significance of the obtained in vitro data is not defined, safety and efficacy of moxifloxacin in the treatment of infections caused by these pathogens in adequate and well-controlled trials has not been established.
Photosensitivity. Study of skin reaction to ultraviolet light (UVA and UVB) and visible radiation, conducted with 32 healthy volunteers (8 per group) showed that moxifloxacin shows no phototoxicity compared to placebo. Minimum erythematous dose (MED) was determined before and after administration of moxifloxacin (200 or 400 mg once daily) or placebo. The MED measured for both doses of moxifloxacin was not significantly different from placebo.
Pharmacokinetics
Absorption. When administered orally, it is well absorbed from the gastrointestinal tract. Absolute bioavailability is almost 90%. Consumption of food with high content of fat (500 calories) has no effect on absorption of moxifloxacin. Simultaneous consumption of 1 cup of yogurt has no significant effect on the degree and rate of systemic absorption (AUC). In studies with healthy volunteers it was shown that Cmax after a single oral intake of 400 mg of moxifloxacin is (3.1±1) mg/l (n=372). Plasma concentration increases in proportion to dose in the dose range up to 1200 mg (maximum single test dose when taken orally). The plasma T1/2 is (12±1.3) h and equilibrium is reached after at least three days of administration (400 mg daily).
Distribution. Binding to serum proteins is approximately 30-50% and is independent of the substance concentration. Vd is 1.7-2.7 l/kg. Well distributed in the tissues and body fluids, with concentrations in the tissues often exceeding the plasma concentration of the substance. After oral administration or IV administration of 400 mg of moxifloxacin is detected in saliva, the mucous membrane of the nose, bronchi and sinuses, subcutaneous tissues, skeletal muscle and abdominal tissues. High concentrations exceeding the level of moxifloxacin in blood are created in the bronchial mucosa (tissue/plasma concentration ratio (1.7±0.3), alveolar macrophages (21.2±10.0), fluid covering the respiratory epithelium (8.7±6.1) mucosa of the maxillary sinus (2.0±0.3), ethmoidal sinus (2.2±0.6), nasal polyps (2.6±0.6), abdominal tissues (2.7±08), abdominal exudate (1.6±0.7), in the contents of blisters in skin inflammation (0.9±0.2), subcutaneous tissue (0.4±0.6), skeletal muscles (0.4±0.1).
The concentrations were measured 3 h after a single dose of 400 mg (except for measurements in abdominal tissue and exudate, which were taken 2 h after moxifloxacin administration, and in the sinuses, which were taken 2 h after moxifloxacin administration after 5 days of use). The elimination rate of moxifloxacin from tissues usually parallels the elimination rate from plasma.
Metabolism. Approximately 52% of the moxifloxacin dose (oral or IV) is metabolized by conjugation to form two inactive metabolites, sulfate (M1) and glucuronide (M2). M1 is approximately 38% of the dose and is excreted primarily with feces, M2 is 14% of the dose and is excreted only with the urine. Peak plasma concentrations of M2 are approximately 40% of the parent substance concentration, while plasma concentrations of M1 are typically less than 10% of the concentration of moxifloxacin.
Moxifloxacin is metabolized without involvement of the cytochrome P450 system (cytochrome P450 system activity is not affected). In vitro studies with cytochrome P450 isoenzymes show that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2.
Excretion. Approximately 45% of moxifloxacin (oral or IV) is excreted unchanged (of which approximately 20% in the urine, about 25% in the feces). (96±4)% of the oral dose is excreted either unchanged or as known metabolites. Total apparent clearance is (12±2) l/h, renal clearance is (2.6±0.5) l/h.
Dependence of pharmacokinetic parameters on some factors
There were no clinically significant differences in pharmacokinetics of moxifloxacin according to age, gender and race of patients.
Elderly age. No age-related changes in pharmacokinetics were observed in 16 elderly (8 men, 8 women) and 17 young (8 men, 9 women) healthy volunteers after oral administration of moxifloxacin at a dose of 400 mg for 10 days. In 16 healthy male volunteers (8 young; 8 elderly) after a single oral dose of moxifloxacin 200 mg the degree of systemic effect (AUC and Cmax) was not different in young and elderly men, T1/2 was not changed. No dose adjustment based on age is required. In large phase III studies moxifloxacin blood concentrations at the end of infusion in elderly patients after an IV infusion of 400 mg were similar to those observed in younger patients.
Paul. After oral administration of 400 mg of moxifloxacin daily for 10 days, 23 healthy men (19-75 years) and 24 healthy women (19-70 years) had mean AUC and Cmax values 8 and 16% higher in women compared with men. The differences were due to differences in body weight rather than sex.
A study of a single dose of 400 mg was conducted with 18 young men and women. A comparison of the pharmacokinetics of moxifloxacin in this study (9 women and 9 men) showed no difference in AUC or Cmax by sex. No adjustment of the dose of moxifloxacin according to sex is required.
Children. Pharmacokinetics of moxifloxacin in children has not been studied.
Race. Pharmacokinetics of moxifloxacin in equilibrium condition after daily oral intake in 400 mg dose in Japanese men was similar to that in European men and was characterized with values of Cmax 4.1 mcg /ml, AUC24 47 mcg-h /ml and T1/2 14 hours.
Renal insufficiency. No significant changes in pharmacokinetic parameters have been found in mild, moderate and severe renal dysfunction (including terminal stage). No dose adjustment is required in patients with renal impairment, including those on continuous hemodialysis and long-term ambulatory peritoneal dialysis.
Hepatic impairment. Dose adjustment is not recommended in mild, moderate and severe hepatic impairment (Child Pugh grades A, B and C). However, due to metabolic disorders associated with hepatic failure, which may lead to prolongation of the QT interval, moxifloxacin should be used with caution in these patients.
Preclinical toxicology
Carcinogenicity. No long-term animal studies have been conducted to evaluate the carcinogenic effects of moxifloxacin.
Mutagenicity. Mutagenicity or genotoxicity was not observed in a number of in vitro tests, including Ames test (using 4 bacterial strains of TA 98, TA 100, TA 1535, TA 1537), test with hypoxanthine-guanine phosphoribosyltransferase of Chinese hamster ovary cells, as well as in vivo (including micronucleus test in mice). Mutagenic activity was revealed (as for other quinolones) in Ames test using bacterial strain TA 102, probably caused by blockade of DNA-gyrase. It showed clastogenic activity in V-79 test for chromosomal aberrations, but did not cause atypical DNA synthesis in rat hepatocyte culture.
The effect on fertility. No effect of moxifloxacin on fertility was detected in male and female rats when administered orally at doses greater than 500 mg/kg/day (approximately 12-fold greater than MRDH, in terms of body surface area) or intravenously at doses of 45 mg/kg/day (approximately identical to MRDH, in terms of body surface area, mg/m2). Small effects on sperm morphology (head and tail separation) in male rats and on the sexual cycle of female rats were observed when doses of 500 mg/kg/day were administered orally.
Toxicology and/or pharmacology in animals
The quinolones cause arthropathy in young growing animals. In studies in dogs, pups have been shown to develop arthropathy on oral administration of moxifloxacin at doses ≥30 mg/kg/day (approximately 1.5 times the MRDH) for 28 days. Oral administration to mature monkeys and rats at doses of 135 and 500 mg/kg/day, respectively, was not accompanied by manifestations of arthropathy.
Some quinolones have proconvulsant activity that is enhanced when combined with NSAIDs. In studies on mice no increase of acute toxicity or potential toxic effect on CNS (including seizures) were found when applying moxifloxacin orally at a dose of 300 mg/kg together with NSAIDs (diclofenac, ibuprofen, fenbufen).
In studies on dogs it was shown that at plasma concentrations of moxifloxacin, 5 times higher than therapeutic levels in humans, prolongation of QT interval was observed. The main mechanism of QT interval prolongation (data from electrophysiological studies) is the inhibition of rapid activating component of delayed (delayed) rectifying potassium current. Simultaneous infusion of sotalol against the background of moxifloxacin administration in dogs led to a more pronounced prolongation of the QT interval c than when taking moxifloxacin alone at the same dose (30 mg/kg).
There were no signs of local intolerance in dogs when administered moxifloxacin by IV injection. Inflammatory changes affecting the periarterial soft tissues have been observed following an IV/a injection of moxifloxacin, suggesting that IV administration should be avoided.
Clinical Studies
The efficacy of moxifloxacin for systemic use has been evaluated in a number of clinical studies.
Acute bacterial sinusitis
The efficacy of moxifloxacin (400 mg once daily orally for 10 days) in treating patients with acute bacterial sinusitis was evaluated in a double-blind, controlled clinical trial conducted in the United States. The clinical efficacy of moxifloxacin (cure plus improvement) was 90%; the primary efficacy analysis was performed on days 7-21 after therapy.
In addition, studies were conducted to obtain bacteriological data to assess microbiological eradication in adult patients when treated with moxifloxacin (400 mg orally, once daily for 7 days). All patients (n=336) underwent an abdominal puncture. The clinical efficacy rate (eradication) at day 21-37 after treatment was 97% (29/30) for Streptococcus pneumoniae, 83% (15/18) for Moraxella catarrhalis, and 80% (24/30) for Haemophilus influenzae.
The exacerbation of chronic bronchitis
. According to the results of a large-scale randomized double-blind controlled clinical trial conducted in the United States, the clinical efficacy of moxifloxacin in the treatment of exacerbations of chronic bronchitis (oral dose of 400 mg once daily for 5 days) was 89% (222/250 patients), with the initial assessment of results on days 7-17 after therapy. The degree of microbiological eradication was: for Streptococcus pneumoniae and Haemophilus parainfluenzae 100% (16/16), Haemophilus influenzae 89% (33/37), Moraxella catarrhalis 85% (29/34), Staphylococcus aureus 94% (15/16), Klebsiella pneumoniae 90% (18/20).
Efficacy of moxifloxacin (oral dosage of 400 mg once daily) in the treatment of patients with clinically and radiographically documented community-acquired pneumonia was evaluated in a randomized, double-blind, controlled clinical trial conducted in the United States. The clinical efficacy of moxifloxacin was 95% (184/194), with an initial efficacy assessment in most patients on days 14-35 at follow-up visits.
A randomized, double-blind, controlled clinical trial conducted in the United States and Canada evaluated the efficacy of moxifloxacin when administered sequentially, v/v, then orally, in a dose of 400 mg once daily for 7-17 days in patients with a confirmed diagnosis of community-acquired pneumonia. The clinical efficacy of moxifloxacin was 86% (157/182), with primary efficacy analysis in most patients on day 7-30 after the end of therapy.
In an open-label study outside the United States, the clinical efficacy of moxifloxacin was 93% (241/258) on day 5-7 and 84% (216/258) 21-28 days after completion of treatment.
. Combined data of 4 researches suggest that degree of clinical effectiveness of moxifloxacin was 85% against Staphylococcus aureus, 92% against Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, 93% against Chlamydia pneumoniae, 94% against Streptococcus pneumoniae, 96% against Mycoplasma pneumoniae.
Out-of-hospital pneumonia caused by strains of Streptococcus pneumoniae with multiple resistance to antibiotics (see “Indications”). The clinical and bacteriological efficacy of moxifloxacin was 95% (35/37).
Uncomplicated infections of the skin and its appendages.
According to the results of a randomized double-blind controlled clinical trial conducted in the USA, in the treatment of skin infections (uncomplicated abscesses – 30%, furuncles – 8%, cellulitis – 16%, impetigo – 20%, other skin infections – 26%) the effectiveness of moxifloxacin (oral administration in a dose of 400 mg once daily for 7 days) was 89% (108/122).
Complicated infections of the skin and its appendages
The efficacy of moxifloxacin was evaluated in two randomized controlled clinical trials with the active drug. In a double-blind trial conducted primarily in North America, the clinical efficacy of moxifloxacin (sequential IV followed by oral administration at a dose of 400 mg once daily for 7-14 days) was 77.2% (125/162). In a second open international study, the clinical efficacy of moxifloxacin in a dose of 400 mg once daily for 7-21 days was 80.6% (254/315). Treatment success rates varied according to the type of diagnosis, ranging from 61% in patients with infected ulcers to 90% in patients with complicated rust inflammation.
The clinical efficacy of moxifloxacin was 82.2% (106/129) against Staphylococcus aureus (methicillin-sensitive strains), 81.6% (31/38) against Esherichia coli, 91.7% (11/12) against Klebsiella pneumoniae, 81.8% (9/11) against Enterobacter cloacae.
Complicated intra-abdominal infections
The efficacy of moxifloxacin has been evaluated in two randomized controlled clinical trials with the active drug. A double-blind study conducted in North America in the treatment of patients with intraabdominal infections such as peritonitis, abscess, appendicitis with perforation, and intestinal perforation reported 79.8% (146/183) effectiveness of moxifloxacin (sequential IV followed by oral administration at a dose of 400 mg once daily for 5-14 days). In a second open-label international study, the efficacy of moxifloxacin (400 mg once daily for 5-14 days c) was 80.9% (199/246).
Plague
The efficacy studies of moxifloxacin could not be conducted in people with pneumonic plague for ethical and feasibility reasons. Therefore, approval of this indication was based on an animal efficacy study and supportive pharmacokinetic data in adult humans and animals.
A randomized, blind, placebo-controlled study was conducted in an animal model of African green monkey pneumonic plague. Twenty monkeys (10 males and 10 females) were exposed to a mean inhalation dose (±standard deviation) of (100±50) LD50 (range 92 to 127 LD50) of Yersinia pestis aerosol (strain CO92). The MPC of moxifloxacin for the Y. pestis strain used in this study was 0.06 µg/mL.
The development of a persistent fever of at least 4 h was used as a trigger for initiating a 10-day administration of either moxifloxacin or placebo. All of the animals studied had fever and bacteremia with Y. pestis before the start of follow-up. Ten of 10 (100%) animals receiving placebo died of the disease between 83 and 139 h (115±19) after infection. Ten of 10 (100%) animals receiving moxifloxacin survived for 30 days after study completion. Compared with the placebo group, mortality was significantly lower in the moxifloxacin group (survival difference: 100% with two-sided 95% CI (66.3%, 100%), p< 0.0001 value).
The mean plasma concentrations of moxifloxacin associated with a statistically significant improvement in survival compared with placebo, in an African green monkey model of pneumonic plague, achieved or exceeded those in adult humans when administered at the recommended oral and intravenous regimens. The mean (±standard deviation) plasma Cmax and total plasma exposure (AUC) in adults treated with 400 mg v/v were (3.9±0.9) µg/ml and (39.3±8.6) µg-h/ml, respectively. The mean (±standard deviation) plasma Cmax and AUC0-24 in monkeys after a one-day simulated dosing regimen simulating the achievement of AUC0-24 in humans at the 400 mg dose were (4.4±1.5) mcg/mL and (22±8) mcg-h/mL, respectively.
Indications
Sinusitis, Respiratory tract infections, Urinary tract infections, Skin infections, Bronchitis, Lung inflammation (pneumonia), Infectious diseases
Infectious and inflammatory diseases caused by microorganisms sensitive to moxifloxacin:
acute sinusitis;
exacerbation of chronic bronchitis;
uncomplicated infections of skin and subcutaneous structures;
Community-acquired pneumonia, including community-acquired pneumonia caused by strains of microorganisms with multiple antibiotic resistance*;
complicated infections of the skin and subcutaneous structures (including infected diabetic foot);
complicated intra-abdominal infections, including polymicrobial infections, includingincluding intraperitoneal abscesses;
uncomplicated pelvic inflammatory diseases (including salpingitis and endometritis).
*Streptococcus pneumoniae with multiple antibiotic resistance includes penicillin-resistant strains and strains resistant to two or more antibiotics from groups such as penicillins (at MIC ≥2 µg/ml), second generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole. Current official guidelines on the use of antibacterials must be taken into account.
Active ingredient
Moxifloxacin
Composition
1 film-coated tablet contains:
Core:
the active ingredient:
moxifloxacin hydrochloride 454.75 mg, equivalent to moxifloxacin 400.00 mg;
auxiliary substances:
Microcrystalline cellulose 186.05 mg,
croscarmellose sodium 32.00 mg,
Magnesium stearate 6.00 mg;
Capsule film:
Hypromellose 12.60 mg, macrogol-4000 4.20 mg, titanium dioxide (E171) 3.78 mg, iron oxide red dye (E172) 0.42 mg.
How to take, the dosage
Overly, 1 tablet (400 mg) once daily for the infections listed above. The recommended dose should not be exceeded. The tablets should be swallowed whole, without chewing, with plenty of water, regardless of the time of meals.
The duration of treatment. Determined by the localization and severity of the infection, as well as the clinical effect:
– exacerbation of chronic bronchitis 5-10 days;
– acute sinusitis 7 days;
– uncomplicated infections of the skin and subcutaneous structures 7 days;
– community-acquired pneumonia total duration of step therapy (IUI followed by oral administration) is 7-14 days;
– complicated infections of the skin and subcutaneous structures – the total duration of step therapy with moxifloxacin (IV infusion followed by oral administration) is 7-21 days;
– Complicated intra-abdominal infections – total duration of step therapy (intravenous infusion followed by oral administration) is 5-14 days;
– uncomplicated inflammatory diseases of the pelvic organs – 14 days.
Do not exceed the recommended duration of treatment. According to clinical studies, the duration of treatment with the drug Moflaxia in tablets can be up to 21 days.
Patient special groups
The elderly. No change in dosing regimen is required in elderly patients.
Children Efficacy and safety of moxifloxacin use in children and adolescents has not been established.
Hepatic impairment. Patients with impaired liver function (classes A and B according to Child-Pugh classification) do not require change of dosage regimen (for use in patients with cirrhosis see “Cautionary Note”).
Renal dysfunction. In patients with impaired renal function (including patients with severe renal failure with creatinine Cl ≤30 ml/min/1.73 m2) as well as in patients on continuous hemodialysis and long-term ambulatory peritoneal dialysis a change of dosing regimen is not required.
Ethnicity. No change in dosing regimen is required in patients of different ethnic groups.
Interaction
In concomitant use with atenolol, ranitidine, calcium-containing supplements, theophylline, cyclosporine, oral contraceptives, glibenclamide, itraconazole, digoxine, morphine, probenecid (no clinically significant interaction with moxifloxacin has been confirmed) no dose adjustment is required.
Drugs prolonging the QT interval. Possible additive effect of QT interval prolongation of moxifloxacin and other drugs which affect the prolongation of the QT interval should be considered. Due to the simultaneous use of moxifloxacin and the medicines affecting the prolongation of the QT interval, the risk of ventricular arrhythmias, including polymorphic ventricular tachycardia, increases.
Continuous use of moxifloxacin with the following medicines which affect QT interval prolongation is contraindicated:
– antiarrhythmic medicines of class IA (incl.
– Class III antiarrhythmic drugs (including amiodarone, sotalol, dofetilide, ibutilide);
– neuroleptics (including phenothiazine, pimotazoleptics). phenothiazine, pimozide, sertindole, haloperidol, sultopride);
Tricyclic antidepressants;
Antimicrobials (sparfloxacin, erythromycin (IV), pentamidine, antimalarials, especially halofantrine);
– antihistamines (terfenadine, astemizole, misolastin);
– others (cisapride, vincamine (w/v), bepridil, difeminate).
Antacids, multivitamins and minerals. Taking moxifloxacin concomitantly with antacids, multivitamins and minerals can lead to impaired absorption of moxifloxacin due to the formation of chelate complexes with multivalent cations contained in these drugs. As a result, plasma concentration of moxifloxacin may be significantly lower than desired. In this regard, antacids, antiretroviral medicines (e.g. didanosine) and other drugs containing magnesium or aluminum, sucralfate and other medicines containing iron or zinc should be used at least 4 hours before or 4 hours after oral administration of moxifloxacin.
Warfarin. When concomitant use with warfarin, PV and other parameters of blood coagulation are not changed.
Change in INR value. In patients who received anticoagulants concomitantly with antibiotics, including moxifloxacin, there are cases of increase in anticoagulant activity of anticoagulants. Risk factors are the presence of infectious disease (and associated inflammatory process), age and general condition of the patient. Although no interaction between moxifloxacin and warfarin was found, in patients receiving these drugs simultaneously, it is necessary to monitor INR and adjust the dose of indirect anticoagulants, if necessary.
Digoxin. Moxifloxacin and digoxin have no significant effect on the pharmacokinetic parameters of each other. When using repeated doses of moxifloxacin, the Cmax of digoxin in plasma was increased by approximately 30%, while the AUC and Cmin of digoxin did not change.
Activated charcoal. When concomitant use of activated charcoal and moxifloxacin at a dose of 400 mg orally the systemic bioavailability of moxifloxacin decreases by more than 80% due to its reduced absorption. In case of overdose, the use of activated charcoal in the early stage of absorption prevents further increase in systemic exposure.
Special Instructions
In some cases hypersensitivity and allergic reactions may develop already after the first use of the drug and the physician should be informed immediately. Very rarely even after the first use of the drug anaphylactic reactions may progress to life-threatening anaphylactic shock. In these cases the treatment with the drug Moflaxia should be stopped and all necessary therapeutic measures (including anti-shock measures) should be started immediately.
When using the drug Moflaxia, prolongation of the QT interval may be observed in some patients. The drug Moflaxia should be used with caution in women and elderly patients. Since women compared to men have a longer QT interval, they may be more sensitive to the drugs prolonging this interval. Older patients are also more susceptible to medications that affect the QT interval.
Long QT interval prolongation is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia.
The degree of QT interval prolongation may increase with increasing plasma concentration of moxifloxacin, so the recommended dose should not be exceeded. However, in patients with pneumonia the correlation between the concentration of moxifloxacin in plasma and prolongation of the QT interval was not observed. None of the 9000 patients who received moxifloxacin had cardiovascular complications and fatalities associated with prolongation of the QT interval. The risk of ventricular arrhythmias may increase in patients with predisposing to arrhythmias when using Mofloxacin.
In this regard, the drug Moflaxia is contraindicated in patients with alterations of electrophysiologic parameters of heart, manifested by prolongation of QT interval (congenital or acquired documented prolongation of QT interval); electrolyte disturbances, especially in unregulated hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; history of rhythm disturbances accompanied by clinical symptoms; in combination with other QT interval prolonging agents (see “Interaction “Interactions”).
The drug Moflaxia should be used with caution:
– in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia and cardiac arrest;
– in patients with cirrhosis (because the risk of QT interval prolongation cannot be excluded in this category of patients).
In case of fulminant hepatitis potentially leading to liver failure (including fatal cases) has been reported when taking moxifloxacin (see “Adverse effects”). The patient should be informed that if symptoms of liver failure occur, a physician should be consulted before continuing treatment with Moflaxia.
When taking moxifloxacin it was reported about the development of bullous skin lesions such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see “Adverse effects”). The patient should be informed that in case of symptoms of skin lesions or mucous membranes it is necessary to consult a physician before continuing treatment with the drug Moflaxia.
The use of quinolone drugs involves a possible risk of seizures. The drug Moflaxia should be used with caution in patients with diseases of the CNS and with CNS disorders predisposing to the occurrence of seizures or reducing the threshold for seizure activity.
The use of broad-spectrum antibacterial agents, including Moflaxia, is associated with the risk of pseudomembranous colitis. This diagnosis should be kept in mind in patients who developed severe diarrhea during treatment with the drug Moflaxia. In this case, appropriate therapy should be prescribed immediately. Drugs which inhibit intestinal peristalsis are contraindicated in severe diarrhea.
The drug Moflaxia should be used with caution in patients with myasthenia gravis due to possible exacerbation of the disease.
With quinolones including moxifloxacin therapy, tendinitis and tendon rupture may develop, especially in elderly patients and patients receiving GCS. Cases have been described that occurred within a few months after completion of treatment. At the first symptoms (pain or inflammation at the site of injury) the drug Moflaxia should be discontinued and the affected limb should be unloaded.
Photosensitivity reactions have been reported with quinolones. However, in preclinical and clinical studies, as well as with the use of moxifloxacin in clinical practice photosensitivity reactions were not observed. Nevertheless, patients receiving the drug Moflaxia should avoid direct sunlight and UV exposure.
The use of Moflaxia in tablet form for oral administration is not recommended in patients with complicated pelvic inflammatory diseases (e.g., those associated with tubo-ovarian or pelvic abscesses).
The use of moxifloxacin for the treatment of infections caused by strains of Staphylococcus aureus that are resistant to methicillin is not recommended. In the case of suspected or confirmed infections caused by MRSA the appropriate antibacterial agents should be used for therapy (see “Pharmacodynamics”). The ability of moxifloxacin to inhibit the growth of mycobacteria may cause interaction under in vitro conditions of moxifloxacin with the test for Mycobacterium spp., which leads to false-negative results in the analysis of samples from patients who are treated with Moflaxia during this period.
In patients treated with quinolones, including moxifloxacin, cases of sensory or sensorimotor polyneuropathy resulting in paresthesia, hypoesthesia, dysesthesia or weakness have been described. Patients treated with Moflaxia should be warned to consult a physician immediately before continuing treatment if symptoms of neuropathy, including pain, burning, tingling, numbness, or weakness occur (see “Side effects”). Mental reactions may occur even after the first use of fluoroquinolones, including moxifloxacin. In very rare cases, depression or psychotic reactions progress to suicidal thoughts and behavior with a tendency to self-harm, including suicide attempts (see “Side effects”). If patients develop such reactions, Moflaxia should be discontinued and appropriate measures taken. Caution should be exercised when using the drug Moflaxia in patients with psychosis and mental illness in the anamnesis.
Because of the high prevalence and increasing incidence of infections caused by Neisseria gonorrhoeae resistant to fluoroquinolones, during the treatment of patients with pelvic inflammatory diseases should not be conducted monotherapy with moxifloxacin, except in cases when the presence of fluoroquinolone-resistant N. gonorrhoeae is excluded. If there is no way to exclude the presence of fluoroquinolone-resistant N. gonorrhoeae, it is necessary to consider supplementing empirical therapy with moxifloxacin with an appropriate antibiotic that is active against N. gonorrhoeae (e.g., cephalosporin).
Dysglycemia
As with other fluoroquinolones, during the use of the drug Moflaxia changes in blood glucose concentration were observed, including hypo-and hyperglycemia. During the therapy with moxifloxacin dysglycemia occurred mainly in elderly patients with diabetes receiving concomitant therapy with hypoglycemic drugs for oral administration (such as sulfonylureas) or insulin. Close monitoring of blood glucose concentrations is recommended during treatment in patients with diabetes mellitus (see “Side effects”).
Impact on the ability to perform potentially hazardous activities requiring particular attention and responsiveness (e.g., driving, operating moving machinery). Fluoroquinolones including moxifloxacin may impair the ability of patients to drive and engage in other potentially dangerous activities requiring particular attention and rapid psychomotor reactions due to the effect on the CNS and visual impairment.
Contraindications
– hypersensitivity to moxifloxacin, other quinolones or any other component of the drug;
– history of tendon pathology developed due to treatment with quinolone antibiotics;
– patients in the following categories: congenital or acquired documented QT interval prolongation, electrolyte abnormalities, especially uncorrected hypokalemia, clinically significant bradycardia, clinically significant chronic heart failure with reduced left ventricular ejection fraction, history of arrhythmias, accompanied by clinical symptomatology (in preclinical and clinical trials after moxifloxacin administration there were changes in electrophysiological parameters of heart, expressed in prolongation of QT interval);
– use with other drugs that prolong the QT interval;
– patients with impaired liver function (class C according to the Child-Pugh classification) and patients with increased transaminase activity more than 5 times the WHR (due to the limited clinical data);
– pregnancy;
– period of breastfeeding;
– age less than 18 years.
With caution: CNS diseases (including.
With caution: CNS diseases (including suspected CNS involvement) which predispose to seizures and decrease the seizure threshold, patients with psychosis and/or other mental illnesses in the history, patients with potentially proarrhythmic conditions (especially in women and elderly patients), such as acute myocardial ischemia and cardiac arrest, patients with cirrhosis of the liver; myasthenia gravis; concomitant administration with potassium-lowering drugs; patients with a genetic predisposition or actual presence of glucose-6-phosphate dehydrogenase deficiency.
Side effects
The data on adverse reactions reported when using moxifloxacin 400 mg (orally, during step therapy (IV administration of moxifloxacin followed by oral administration) and only IV) were obtained from clinical trials and post-marketing reports (italicized). Adverse reactions listed in the “frequently” group occurred with an incidence of less than 3%, with the exception of nausea and diarrhea.
The frequency was classified as follows: frequently (?1/100 to < 1/10); infrequently (?1/1000 to < 1/100); rarely (?1/10000 to < 1/1000); very rarely (< 1/10000).
In each group, the undesired effects are listed in descending order of importance.
Table 3
System-organ classes and conditions (MedDRA) | Frequency of adverse reactions | ||||||||
Frequently | Infrequently | Rarely | |||||||
Infectious and parasitic diseases | Fungal superinfections | ||||||||
Blood and lymphatic system side | Anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia, prolongation of PV/increase of INR | Change in plasma thromboplastin concentration | /td> | Increased prothrombin concentration/ decreased INR | |||||
Immune system side | Allergic reactions, skin itching, skin rash, urticaria, eosinophilia | Anaphylactic/anaphylactoid reactions, angioedema (including potentially life-threatening laryngeal edema) | Anaphylactic/anaphylactoid shock (incl.ч. potentially life-threatening) | ||||||
Metabolic and nutritional disorders | Hyperlipidemia | Hyperglycemia, hyperuricemia | Hypoglycemia | ||||||
Mental disorders | Anxiety, psychomotor hyperactivity/anxiety | Emotional lability, depression (in very rare cases, potentially self-harming behavior such as suicidal thoughts or suicide attempts), hallucinations | Depersonalization, psychotic reactions (potentially manifesting in self-harming behavior such as suicidal thoughts or suicide attempts) | ||||||
Nervous system disorders | Headache, dizziness | Paresthesia/dysesthesia, impaired taste sensitivity (including in very rare cases agueusia), confusion and disorientation, sleep disturbances, tremor, vertigo, somnolence | Hypoesthesia, olfactory disturbances (including anosmia), atypical dreams, poor coordination (including gait disturbances due to vertigo or vertigo, in very rare cases leading to injuries from falls, especially in elderly patients), seizures with various clinical manifestations (includingч. grand mal seizures), attention deficits, speech disorders, amnesia, peripheral neuropathy and polyneuropathy | Hyperesthesia | |||||
Visually impaired | Visual disturbances (especially with CNS reactions) | Transient visual loss (especially with CNS reactions) | |||||||
Hearing organ and labyrinth disorders | Tinnitus, hearing impairment, including deafness (usually reversible) | ||||||||
Heart and vascular disorders | QT interval prolongation in patients with concomitant hypokalemia | QT interval prolongation, palpitations, tachycardia, vasodilation | Ventricular tachyarrhythmias, syncope, increased/decreased BP | Nonspecific arrhythmias, polymorphic ventricular tachycardia, cardiac arrest (primarily in individuals with arrhythmia-predisposing conditions such as clinically significant bradycardia, acute myocardial ischemia) | |||||
Respiratory system, thoracic and mediastinal organs | Shortness of breath (including asthmatic conditions) | ||||||||
Gastrointestinal side | Nausea, vomiting, abdominal pain, diarrhea | Reduced appetite and reduced food intake, constipation, dyspepsia, flatulence, gastroenteritis (except erosive gastroenteritis), increased plasma amylase activity | Dysphagia, stomatitis, pseudomembranous colitis (in very rare cases associated with life-threatening complications) | ||||||
Liver and biliary tract side | Increased liver transaminase activity | Liver function abnormalities (including increased LDH activity), increased bilirubin concentration, increased GGT activity, increased ALP activity in plasma | Jaundice, hepatitis (predominantly cholestatic) | Biliary tract disorders | Fulminant hepatitis, potentially leading to life-threatening liver failure (including fatal cases) | ||||
Skin and subcutaneous tissue side | Bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening) | ||||||||
Musculoskeletal and connective tissue side | Arthralgia, myalgia | Tendinitis, increased muscle tone and cramps, muscle weakness | Tendon ruptures, arthritis, gait disturbances due to musculoskeletal damage, worsening symptoms of myasthenia gravis | ||||||
Renal and urinary tract side | Dehydration (caused by diarrhea or decreased fluid intake) < | Renal dysfunction, renal failure (as a result of dehydration, which may lead to renal damage, especially in elderly patients with pre-existing renal dysfunction) | /td> | ||||||
General disorders and disorders at the injection site | Reactions at the injection/infusion site | General malaise, nonspecific pain, increased sweating, phlebitis/thrombophlebitis at the infusion site | Oedema |
The incidence of the following adverse reactions was higher in the group that received step therapy: frequently, increased GGT activity; infrequently, ventricular tachyarrhythmias, decreased BP, edema, pseudomembranous colitis (in very rare cases associated with life-threatening complications), seizures with various clinical manifestations (includingincluding grand mal seizures), hallucinations, renal dysfunction, and renal failure (as a result of dehydration, which may lead to renal damage, especially in elderly patients with pre-existing renal dysfunction).
Overdose
There are limited data on overdose of moxifloxacin. No adverse effects were observed when using moxifloxacin in dose up to 1200 mg once and 600 mg for 10 days or more.
Treatment: in case of overdose the clinical picture should be guided and symptomatic supportive therapy with ECG-monitoring should be conducted. The use of activated charcoal immediately after ingestion may help prevent excessive systemic exposure to moxifloxacin in case of overdose.
Pregnancy use
The safety of moxifloxacin use during pregnancy has not been established, so its use is contraindicated. Cases of reversible joint damage in children receiving some quinolones have been described, but no manifestation of this effect in the fetus has been reported (when used by the mother during pregnancy).
Reproductive toxicity has been identified in animal studies. The potential risk to humans is unknown.
Like other quinolones, moxifloxacin causes cartilage damage of large joints in premature animals.
In preclinical studies it was found that a small amount of moxifloxacin is excreted into breast milk. There are no data on its use in women during lactation. Therefore, the use of moxifloxacin during breastfeeding is contraindicated.
Similarities
Avelox, Vigamox, Moxifloxacin, Kimox
Weight | 0.022 kg |
---|---|
Shelf life | 2 years. Do not use the drug after the expiration date. |
Conditions of storage | At a temperature not exceeding 25 ° C, in the original package. Store out of the reach of children. |
Manufacturer | KRKA dd Novo mesto, Slovenia |
Medication form | pills |
Brand | KRKA dd Novo mesto |
Related products
Buy Moflaxia, 400 mg 7 pcs with delivery to USA, UK, Europe and over 120 other countries.