Instructions for use AVELOX® (AVALOX)
In some cases, hypersensitivity and allergic reactions may develop after the first use of the drug. Very rarely, anaphylactic reactions can progress to life-threatening anaphylactic shock even after the first use of the drug. In these cases, moxifloxacin should be discontinued and the necessary therapeutic measures (including anti-shock) should be taken.
QT interval prolongation may occur in some patients when using moxifloxacin.
Given that women tend to prolong the QT interval compared to men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients are also more sensitive to drugs that affect the QT interval. The degree of QT interval prolongation may increase with increasing drug concentrations, so the recommended dose should not be exceeded. Prolongation of the QT interval is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. However, in patients with pneumonia, there was no correlation between moxifloxacin plasma concentrations and QT interval prolongation. None of the 9000 patients treated with moxifloxacin experienced cardiovascular complications or deaths associated with QT prolongation. However, in patients with conditions predisposing to arrhythmias, the risk of developing ventricular arrhythmias may increase when using moxifloxacin.
In this regard, the use of moxifloxacin should be avoided in patients with QT prolongation, uncorrected hypokalemia, as well as in those receiving class IA (quinidine, procainamide) or class III antiarrhythmic drugs (amiodarone, sotalol), since experience with the use of moxifloxacin in these patients organic Moxifloxacin should be used with caution as an additive effect of moxifloxacin cannot be excluded in the following conditions:
- in patients receiving concomitant treatment with drugs that prolong the QT interval (cisapride, erythromycin, antipsychotic drugs, tricyclic antidepressants);
- in patients with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia;
- in patients with liver cirrhosis, since the presence of QT interval prolongation in them cannot be excluded;
- in women or elderly patients who may be more sensitive to drugs that prolong the QT interval.
Cases of fulminant hepatitis, potentially leading to life-threatening liver failure, including death, have been reported. If signs of liver failure appear, patients should immediately consult a doctor before continuing treatment.
Bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening) have been reported. If reactions occur on the skin and/or mucous membranes, you should also immediately consult your doctor before continuing treatment. The use of quinolone drugs is associated with a possible risk of developing a seizure. Moxifloxacin should be used with caution in patients with diseases of the central nervous system and with conditions suspected of involving the central nervous system, predisposing to the occurrence of seizures or lowering the seizure threshold.
The use of broad-spectrum antibacterial drugs, including moxifloxacin, is associated with the risk of developing antibiotic-associated pseudomembranous colitis. This diagnosis should be considered in patients who experience severe diarrhea during treatment with moxifloxacin. In this case, appropriate therapy should be prescribed immediately. Drugs that inhibit intestinal motility are contraindicated in patients who have severe diarrhea.
Avelox should be used with caution in patients with myasthenia gravis, as the drug may exacerbate the symptoms of this disease.
During therapy with fluoroquinolones, including moxifloxacin, tendonitis and tendon rupture may develop, especially in the elderly and patients receiving glucocorticosteroids. At the first symptoms of pain or inflammation at the site of injury, the drug should be stopped and the affected limb should be unloaded.
For patients with complicated inflammatory diseases of the pelvic organs (for example, associated with tubo-ovarian or pelvic abscesses), for whom IV treatment is indicated, taking Avelox 400 mg tablets is not recommended.
When using quinolones, photosensitivity reactions are observed. However, during preclinical and clinical studies, as well as when using moxifloxacin in practice, no photosensitivity reactions were observed. However, patients receiving moxifloxacin should avoid direct sunlight and ultraviolet radiation.
Prolongation of the QTc interval and potentially associated clinical conditions
Moxifloxacin has been found to prolong the QTc interval in electrocardiograms of some patients. In an analysis of ECGs obtained as part of a clinical trial program, the prolongation of the QTc interval when taking moxifloxacin was 6 milliseconds ± 26 milliseconds, which is equal to 1.4% compared to baseline. Because the baseline QTc interval is longer in women than in men, women may be more susceptible to the effects of QTc prolonging drugs. Elderly people are also more susceptible to the drug's effects on the QT interval. Precautions should be taken when prescribing drugs that may decrease potassium levels to patients taking moxifloxacin.
Precautions should be taken when prescribing moxifloxacin to people with current proarrhythmogenic conditions (especially women and the elderly), such as acute myocardial ischemia or QT prolongation, which may increase the risk of developing ventricular arrhythmias (including torsades de pointes) and cardiac arrest. The degree of QT prolongation increases with increasing drug concentrations. Therefore, the recommended dose should not be exceeded.
If symptoms of cardiac arrhythmia occur during treatment with moxifloxacin, you should stop taking the drug and have an ECG.
Impact on the ability to drive vehicles and operate machinery
Fluoroquinolones, including moxifloxacin, may impair the ability to drive or operate machinery due to CNS reactions.
Pharmacological properties of the drug Avelox
Moxifloxacin (1-cyclopropyl-7{(S,S)-2,8-diaza-bicyclo[4.3.0]non-8-ue}-6-fluoro-8-methoxy-1,4-dihydro-4-oxo -3-quinolinecarboxylic acid hydrochloride) is a broad-spectrum fluoroquinolone antibacterial drug. The bactericidal effect of the drug is due to the inhibition of bacterial topoisomerases II and IV, which leads to disruption of DNA biosynthesis of the microbial cell and its death. The activity of moxifloxacin depends on its concentration in the blood plasma: the minimum bactericidal concentrations correspond to the minimum bacteriostatic concentrations. The mechanisms of resistance of microorganisms that inactivate penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not affect the antibacterial effectiveness of moxifloxacin. Cross-resistance between the drug Avelox and the listed antibiotics has not been observed. There were also no cases of plasmid resistance. The overall incidence of resistance is very low (10-7–10-10). Resistance to moxifloxacin develops slowly through numerous mutations. Repeated action of moxifloxacin on microorganisms at concentrations below the minimum inhibitory concentration (MIC) is accompanied by only a slight increase in the MIC. Cross-resistance is usually observed between antibacterial agents of the quinolone group. However, some gram-positive and anaerobic microorganisms that are resistant to other quinolones are sensitive to moxifloxacin. Moxifloxacin in vitro against a wide range of gram-negative and gram-positive microorganisms, anaerobes, acid-fast bacteria and atypical forms such as Micoplasma, Chlamydia, Legionella . Moxifloxacin is effective against bacteria resistant to β-lactam and macrolide antibiotics. The following are sensitive to the drug: gram-positive microorganisms - Staphylococcus aureus (including strains sensitive to methicillin), Streptococcus pneumoniae (including strains resistant to penicillin and macrolides), Streptococcus pyogenes (group A); gram-negative microorganisms - Haemophillus influenzae (including strains producing β-lactamases), Haemophillus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including strains producing β-lactamases), Escherichia coli, Enterobacter cloacae ; atypical forms - Chlamydia pneumoniae, Mycoplasma pneumoniae , Legionella pneumoniae . The following gram-positive microorganisms are relatively sensitive to moxifloxacin: Streptococcus milleri, Str. mitior, Str. agalactiae, Str. dysgalactiae, Staphylococcus cohnii, S. epidermidis (including methicillin-resistant strains), S. haemolyticus, S. hominis, S. saprophyticus, S. 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 ; anaerobes - Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Fusobacterium spp., Porphyromonas spp., Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus, Prevotella sp p., Propionibacterium spp., Clostridium perfringens, Clostridium ramosum ; atypical forms - Legionella pneumophila, Caxiella burnettii. Sensitivity to moxifloxacin was confirmed by clinical data. Moxifloxacin is less active against Pseudomonas aeruginosa, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia. When taken orally, moxifloxacin is absorbed quickly and almost completely. Absolute bioavailability reaches almost 91%. In the dose range from 50 to 1200 mg for a single dose and at a dose of 600 mg/day for 10 days, the pharmacokinetics are linear. Stable blood concentrations are achieved after 3 days of use. After a single dose of 400 mg of the drug, the maximum concentration in the blood plasma is reached within 0.5–4 hours and is 3.1 mg/l. When taking moxifloxacin simultaneously with food, there is a slight increase in the time to reach maximum concentration (by 2 hours) and a slight decrease in maximum concentration (by approximately 16%), while the duration of absorption does not change. However, these data are not clinically significant and the drug can be taken regardless of meals. Moxifloxacin is rapidly distributed in tissues and organs and binds to plasma proteins (mainly albumin) by approximately 45%. The volume of distribution is approximately 2 l/kg. High concentrations of the drug, exceeding the concentration in the blood plasma, are achieved in the lung tissue (alveolar macrophages), bronchial mucosa, paranasal sinuses and especially in areas of inflammation. In interstitial fluid and saliva, moxifloxacin is determined in a free state, not bound to proteins, in a higher concentration than in blood plasma. Moxifloxacin does not undergo biotransformation by the microsomal cytochrome P450 system in the liver and is excreted from the body by the kidneys both unchanged and in the form of inactive sulfo compounds and glucuronides. 45% of the unchanged drug is excreted in urine and feces. The half-life of the drug is approximately 12 hours. The average total clearance after administration of a dose of 400 mg is 179–246 ml/min. About 19% of a single dose is excreted unchanged in the urine and 25% in feces. Age (not studied in children) and sex differences in the pharmacokinetics of moxifloxacin have not been established. There were no significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function (creatinine clearance 30 ml/min•1.73 m2) and in those on continuous hemodialysis and long-term ambulatory peritoneal dialysis. In patients with minor and moderate liver dysfunction (stages A and B according to the Child-Pugh classification), the pharmacokinetics of the drug does not change. There are no data on use in cases of severe liver dysfunction (Child-Pugh stage C).
Avelox drug interactions
Antacids, minerals and multivitamins. The combined use of moxifloxacin with antacids, minerals and multivitamins may cause malabsorption of the drug due to the formation of chelate complexes with polyvalent cations contained in these drugs, and this may in turn lead to a decrease in their concentration in the blood plasma. Therefore, antacids, antiretrovirals and other drugs containing calcium, magnesium, aluminum, iron should be taken at least 4 hours before or 2 hours after oral administration of moxifloxacin. Ranitidine The combined use of ranitidine and moxifloxacin slightly changes the absorption of the latter. Drugs containing calcium When moxifloxacin was combined with high doses of drugs containing calcium, no clinically significant effect on the absorption of moxifloxacin was detected, with the exception of a slight decrease in the rate of absorption. Theophylline Moxifloxacin does not affect the pharmacokinetics of theophylline (and vice versa), therefore, does not interact with isoenzymes of cytochrome P450 subtype 1A2. Warfarin When moxifloxacin is used in combination with warfarin, prothrombin time and other blood coagulation parameters do not change. But sometimes in patients receiving anticoagulants simultaneously with fluoroquinolones, cases of increased anticoagulant activity of antithrombotic drugs were noted. Risk factors are the presence of infectious diseases (and concomitant inflammatory process), age and general condition of the patient. Therefore, in the case of combined use of warfarin and moxifloxacin, it is necessary to adjust the dose of oral antithrombotic drugs. Oral contraceptives No interactions were observed between moxifloxacin and oral contraceptives. Antidiabetic agents No clinically significant interaction has been established between glibenclamide and moxifloxacin. Itraconazole When combined with moxifloxacin, the AUC of itraconazole changes slightly. There was no significant mutual influence of the drugs, so there is no need to change the dosage regimen of any of the drugs. Digoxin The pharmacokinetics of digoxin did not change under the influence of moxifloxacin and vice versa. Morphine With parenteral administration of morphine and simultaneous oral administration of moxifloxacin, a decrease in the bioavailability of the latter was not noted; The maximum concentration of moxifloxacin in blood plasma decreases slightly (17%). Atenolol The pharmacokinetics of atenolol are slightly altered by moxifloxacin. After taking a single dose, the AUC of atenolol increases by 4%, and the maximum plasma concentration decreases by 10%. Probenecid Probenecid does not affect the total and renal clearance of moxifloxacin, so there is no need for dose adjustment when used in combination. Infusion solution of moxifoloxacin is incompatible with solutions of sodium chloride 10% and 20%, sodium bicarbonate 4.2% and 8.4%. The drug should not be administered simultaneously with other antibiotics.
Side effects of the drug Avelox
Moxifloxacin is well tolerated in most patients. During clinical trials of moxifloxacin, the majority of adverse events (90%) were mild or moderate in severity. The rate of discontinuation of treatment using the Avelox infusion solution due to the development of side effects did not exceed 3.8%. With a development frequency of ≥1%≤10% From the cardiovascular system - prolongation of the QT in patients with concomitant hypokalemia. From the gastrointestinal tract - abdominal pain, nausea, diarrhea, vomiting, symptoms of dyspepsia, changes in liver tests. From the central nervous system, sensory organs - dizziness, headache. With a development frequency of ≥0.1%≤1% General reactions - asthenia, hyperhidrosis, general weakness, pain in the chest area. From the cardiovascular system - tachycardia, increased blood pressure, palpitations, prolongation of the QT interval. From the gastrointestinal tract - dry mouth, nausea, vomiting, flatulence, constipation, stomatitis, lack of appetite, oral candidiasis, glossitis, increased gamma-glutamyl transpeptidase and amylase. From the blood and lymphatic system - leukopenia, decreased prothrombin levels, eosinophilia, thrombocytopenia. From the musculoskeletal system - arthralgia, myalgia. From the nervous system - insomnia, dizziness, nervousness, drowsiness, anxiety, tremor, paresthesia. From the respiratory system - shortness of breath. On the skin - rashes, itching, sweating. From the genitourinary system - vaginal candidiasis, vaginitis. With an incidence of ≥0.01%≤0.1% General reactions - pelvic pain, facial swelling, back pain, changes in laboratory tests, allergic reactions, leg pain. From the cardiovascular system - decreased blood pressure, loss of consciousness, peripheral edema, vasodilation (flush of blood to the face). From the gastrointestinal tract - gastritis, discoloration of the tongue, dysphagia, jaundice (predominantly cholestatic), diarrhea (caused by Clostridium difficile ). From the blood and lymphatic system - decreased thromboplastin levels, increased prothrombin levels, thrombocytopenia, anemia. From the metabolic side - hyperglycemia, hyperlipidemia, hyperuricemia, increased LDH in combination with abnormal liver tests. From the musculoskeletal system - arthritis, tendon damage. From the nervous system - hallucinations, depersonalization, increased muscle tone, loss of coordination, agitation, amnesia, aphasia, emotional lability, disturbances in sleep, speech, thinking, decreased tactile sensitivity, pathological dreams, convulsions, confusion, depression. From the respiratory system - bronchospasm. On the skin - rashes (maculopapular, pustular, purpura), urticaria. From the senses - tinnitus, blurred vision, loss of taste, parosmia (including changes in the sense of smell, decrease and loss of smell), amblyopia. From the genitourinary system - impaired renal function (increased creatinine or urea levels). With a development frequency of ≤0.01% Allergic reactions - anaphylactic reactions, anaphylactic shock (including life-threatening), angioedema (including laryngeal edema, life-threatening). From the gastrointestinal tract - pseudomembranous colitis (in isolated cases life-threatening), hepatitis (mainly cholestatic). From the musculoskeletal system - tendon rupture. On the skin side - Stevens-Johnson syndrome. From the nervous system - psychotic reactions. From the cardiovascular system - ventricular tachyarrhythmia (very rare), ventricular fibrillation and flutter and cardiac arrest, mainly in people prone to arrhythmia. From the laboratory parameters - an increase or decrease in the hematocrit value and a decrease or increase in the content of red blood cells, leukocytosis, hypoglycemia, decrease in hemoglobin, increase in the level of alkaline phosphatase, ALT, AST, bilirubin, uric acid, creatinine, urea. The relationship between changes in these laboratory parameters and the use of moxifloxacin has not been established.
Overdose of the drug Avelox, symptoms and treatment
No side effects were observed when using Avelox in healthy volunteers in single doses of up to 1.2 g or at a dose of 600 mg/day for 10 days. In case of overdose, symptomatic therapy is carried out, combined with ECG monitoring, in accordance with the clinical situation. The use of activated carbon is advisable only in case of an overdose of moxifloxacin in tablet form; this will prevent systemic exposure to moxifloxacin at an early stage. After its intravenous administration, activated carbon slightly (20%) reduces the systemic exposure of the drug.
Indications for use of the drug Avelox
Treatment of bacterial infections caused by microorganisms sensitive to the drug. Infectious diseases of the respiratory tract:
- chronic bronchitis during exacerbation;
- community-acquired pneumonia, the causative agents of which are strains of microorganisms with multiple resistance to antibiotics;
- acute sinusitis;
Uncomplicated skin and soft tissue infections. Uncomplicated inflammatory diseases of the pelvic organs (including infectious diseases of the upper genital area in women, including salpingitis and endometritis). Complicated infectious diseases of the skin and subcutaneous structures (including infected diabetic foot). Complicated intra-abdominal infections, including polymicrobial infections (such as abscess formation). Streptococcus pneumonie with multiple resistance to antibiotics, including strains resistant to penicillin and strains resistant to two or more antibiotics of such groups as penicillins (with minimal inhibitory activity ≥2 μg/ml), second generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole.
