Rotomox, 400 mg, film-coated tablets, 5 pcs.
In some cases, after the first use of the drug, hypersensitivity and allergic reactions may develop, which should be reported to your doctor immediately. Very rarely, even after the first use of the drug, anaphylactic reactions can progress to life-threatening anaphylactic shock. In these cases, treatment with moxifloxacin should be stopped and the necessary therapeutic measures (including anti-shock) should be started immediately.
QT interval prolongation may occur in some patients when using moxifloxacin. Moxifloxacin should be used with caution in women and elderly patients. Because women have a longer QT interval than men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients are also more susceptible to drugs that affect the QT interval.
Prolongation of the QT interval is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia.
The degree of QT interval prolongation may increase with increasing drug concentrations, so the recommended dose should not be exceeded. However, in patients with pneumonia, no correlation was observed between moxifloxacin plasma concentrations and QT interval prolongation.
There were no cardiovascular complications or deaths associated with QT interval prolongation in patients. When using moxifloxacin, the risk of developing ventricular arrhythmias may increase in patients with conditions predisposing to arrhythmias.
In this regard, moxifloxacin is contraindicated in:
- changes in electrophysiological parameters of the heart, expressed in prolongation of the QT interval: congenital or acquired documented prolongation of the QT interval, electrolyte disturbances, especially uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; a history of rhythm disturbances accompanied by clinical symptoms;
- use with other drugs that prolong the QT interval (see section “Interaction with other drugs”),
Moxifloxacin should be used with caution:
- in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia and cardiac arrest;
- in patients with liver cirrhosis (since in this category of patients the risk of developing a prolongation of the QT interval cannot be excluded).
Cases of fulminant hepatitis, potentially leading to liver failure (including fatal cases), have been reported with the use of moxifloxacin (see section "Side effects"). The patient should be informed that if symptoms of liver failure occur, it is necessary to consult a doctor before continuing treatment with moxifloxacin.
Cases of the development of bullous skin lesions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported (see section "Side effects"). The patient should be informed that if symptoms of skin or mucous membrane lesions occur, they should consult a doctor before continuing treatment with moxifloxacin.
The use of quinolone drugs is associated with a possible risk of developing seizures. Moxifloxacin should be used with caution in patients with diseases of the central nervous system and with disorders of the central nervous system that predispose to seizures or lower the threshold for seizure activity.
The use of broad-spectrum antibacterial drugs, including moxifloxacin, is associated with a risk of developing pseudomembranous colitis. This diagnosis should be considered in patients who develop severe diarrhea during treatment with moxifloxacin. In this case, appropriate therapy should be prescribed immediately. Drugs that inhibit intestinal motility are contraindicated in the development of severe diarrhea.
Moxifloxacin should be used with caution in patients with myasthenia gravis due to possible exacerbation of the disease.
During therapy with quinolones, including moxifloxacin, tendonitis and tendon rupture may develop, especially in the elderly and patients receiving glucocorticosteroids. Cases have been described that occurred within several months after completion of treatment. 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. When using quinolones, photosensitivity reactions are observed. However, during preclinical and clinical studies, as well as with the use of moxifloxacin in practice, no photosensitivity reactions were observed. However, patients receiving moxifloxacin should avoid exposure to direct sunlight and ultraviolet light.
The use of the drug in the form of tablets for oral administration is not recommended in patients with complicated inflammatory diseases of the pelvic organs (for example, associated with tubo-ovarian or pelvic abscesses).
The use of moxifloxacin is not recommended to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In cases of suspected or confirmed infections caused by MRSA, treatment with appropriate antibacterial drugs should be prescribed (see section "Pharmacodynamics").
The ability of moxifloxacin to inhibit the growth of mycobacteria may cause in vitro interaction between moxifloxacin and the test for Mycobacterium spp., leading to false-negative results when analyzing samples from patients who are being treated with moxifloxacin during this period.
In patients treated with quinolones, including moxifloxacin, cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia or weakness have been described. Patients treated with moxifloxacin should be warned to seek immediate medical attention before continuing treatment if symptoms of neuropathy, including pain, burning, tingling, numbness or weakness, occur (see section "Side Effects").
Psychiatric reactions may occur even after the first use 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 (see section "Side effects"). If patients develop such reactions, moxifloxacin should be discontinued and the necessary measures taken. Caution should be exercised when using moxifloxacin in patients with psychosis and/or a history of psychiatric illness.
Due to the widespread and increasing incidence of infections caused by fluoroquinolone-resistant Neisseria gonorrhoeae, patients with pelvic inflammatory disease should not be treated with moxifloxacin monotherapy unless the presence of fluoroquinolone-resistant N. gonorrhoeae has been excluded. If the presence of fluoroquinolone-resistant N. gonorrhoeae cannot be excluded, consideration should be given to supplementing empiric moxifloxacin therapy with an appropriate antibiotic that is active against N. gonorrhoeae (eg, a cephalosporin).
Dysglycemia
As with other fluoroquinolones, changes in blood glucose concentrations, including hypo- and hyperglycemia, were observed with the use of moxifloxacin. During therapy with moxifloxacin, dysglycemia occurred predominantly in elderly patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When conducting treatment in patients with diabetes mellitus, careful monitoring of blood glucose concentrations is recommended (see section “Side Effects”).
Impact on the ability to drive vehicles and machinery
Fluoroquinolones, including moxifloxacin, may impair the ability of patients to drive a car and engage in other potentially hazardous activities that require increased attention and speed of psychomotor reactions due to their effects on the central nervous system and visual impairment.
Compound
1 tablet contains: Active substance: moxifloxacin hydrochloride 436.80 is equivalent to moxifloxacin 400.00 mg. Excipients: corn starch 188.46 mg, sodium methyl parahydroxybenzoate 0.015 mg, microcrystalline cellulose 55.00 mg, talc 7.00 mg, colloidal silicon dioxide 4.00 mg, magnesium stearate 14.00 mg, sodium carboxymethyl starch 24.00 mg. Shell composition: Opaglass (shellac 60.0%, carnauba wax 25.0%, ethanol 10.0%, white beeswax 5.0%) - 0.035 mg; Opadry pink (polyvinyl alcohol 58.0%, talc 3.0%, titanium dioxide 30.0%, macrogol 6.3%, lecithin 1.7%, red iron oxide dye 1.0%) - 0.70 mg.
Side effects
Allergic reactions: urticaria, rash, itching, anaphylactic/anaphylactoid reactions, angioedema, including swelling of the face, larynx (potentially life-threatening), Stevens-Johnson syndrome, toxic epidermal, necrolysis, anaphylactic shock. From the digestive system: abdominal pain, nausea, vomiting, diarrhea, increased activity of “liver” transaminases, flatulence, constipation, lack of appetite, stomatitis, glossitis, transient dysfunction of the liver, discoloration of the tongue, jaundice, gastroenteritis, pseudomembranous colitis, hepatitis (mainly cholestatic), fulminant hepatitis. From the nervous system: headache, pain, dizziness, insomnia or drowsiness, pathological dreams; hallucinations, anxiety, increased muscle tone, impaired coordination of movements, agitation; amnesia, paresthesia, hypoesthesia, hyperesthesia, dysesthesia, tremor, disorientation, psychomotor hyperactivity, emotional lability, speech disorders, attention disorders, convulsions, confusion, depression, depersonalization, psychotic reactions with behavioral disorders with self-harm. From the senses: visual impairment (blurredness, decreased visual acuity), impaired taste sensitivity, loss of taste sensitivity, tinnitus, impaired sense of smell, anosmia. From the cardiovascular system: prolongation of the QT interval (often in patients with concomitant hypokalemia), palpitations, nonspecific arrhythmias, tachycardia, increase and decrease in blood pressure, pain in the chest, fainting, vasodilation/flushing face), ventricular tachyarrhythmias, polymorphic ventricular tachycardia, cardiac arrest (mainly in persons with conditions predisposing to arrhythmia, such as clinically significant bradycardia, acute myocardial ischemia). From the respiratory system: shortness of breath, asthmatic condition. From the musculoskeletal system: arthralgia, myalgia, tendonitis, back pain, leg pain, arthritis, tendon ruptures, increased symptoms of myasthenia gravis. From the genitourinary system: vaginal candidiasis, vaginitis, lower abdominal pain, facial swelling, peripheral edema, renal dysfunction, renal failure Laboratory indicators: anemia, leukopenia, neutropenia, thrombocytopenia, leukocytosis, increase in prothrombin time, increase/decrease in international normalized ratio, eosinophilia, thrombocytosis, changes in the concentration of thromboplastin and prothrombin, increased activity of gamma-glutamine transferase, lactate dehydrogenase, alkaline phosphatase, amylase, increased concentration bilirubin, decreased prothrombin time, hyperglycemia, hyperlipidemia, hyperuricemia. Other: candidiasis, general discomfort, asthenia, sweating.
How to use Rotomox
Recommended dosage regimen for moxifloxacin: 400 mg (1 tablet) once a day. Do not exceed the recommended dose. The tablet should be swallowed whole, without chewing, with plenty of water, regardless of meals. Duration of therapy. The duration of treatment is determined by the location and severity of the infection, as well as the clinical effect. Exacerbation of chronic bronchitis: 5 days. Acute sinusitis: 7 days. Uncomplicated skin and soft tissue infections: 7 days. Community-acquired pneumonia: 7-14 days. Complicated infections of the skin and subcutaneous structures: 7-21 days. Complicated intra-abdominal infections: 5-14 days. Uncomplicated pelvic infections: 14 days. The recommended duration of treatment should not be exceeded. Elderly patients No change in dosage regimen is required in elderly patients. Impaired liver function Patients with impaired liver function (Child-Pugh class A, B) do not require a change in dosage regimen. Renal failure In patients with impaired renal function (including creatinine clearance
Contraindications
- hypersensitivity to moxifloxacin or other quinolones, as well as to any of the auxiliary components of the drug - children and adolescents under 18 years of age - pregnancy and lactation - epilepsy patients with tendon diseases/damage associated with treatment with quinolones (history) In preclinical studies and Studies in humans have found changes in cardiac electrophysiology with the use of moxifloxacin, representing prolongation of the QT interval. Therefore, for safety reasons, moxifloxacin is contraindicated in the following cases: congenital or acquired (documented) prolongation of the QT interval; electrolyte imbalance, in particular, uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with a decrease in left ventricular ejection fraction; history of symptomatic arrhythmia; Moxifloxacin should not be used concomitantly with other drugs that prolong the QT interval. Due to limited class
Indications
Moxifloxacin is indicated for the treatment of the following bacterial infections caused by susceptible microorganisms in patients 18 years of age and older. Moxifloxacin should be prescribed only when it is inappropriate to use the antibacterial drugs recommended for the initial treatment of these infections or when they are ineffective: - exacerbation of chronic bronchitis (adequately diagnosed) - community-acquired pneumonia, except in severe cases - acute bacterial sinusitis - mild to pelvic inflammatory disease moderate severity (infections of the upper female genital tract, including salpingitis and endometritis), not associated with tubo-ovarian or pelvic abscess. Not recommended for use in monotherapy of mild to moderate pelvic inflammatory disease, but should be used in combination with another suitable antibacterial agent (eg, cephalosporin) if resistance to Neisseria gonorrhoeae cannot be excluded.
Drug interactions
The possible additive effect of prolonging the QT interval should be considered when taking moxifloxacin and other drugs that may prolong the QTc interval. Due to the combined use of moxifloxacin and drugs that affect the QT interval, the risk of developing ventricular arrhythmias, including polymorphic ventricular tachycardia (torsade de pointes), increases. Concomitant use of moxifloxacin with any of the following drugs is contraindicated: - Class IA antiarrhythmic drugs (for example, quinidine, hydroquinidine, disopyramide) - Class III antiarrhythmic drugs (for example, amiodarone, sotalol, dofetilide, ibutilide) - antipsychotics (for example, phenothiazines, pimozide, sertindole , haloperidol, sultopride) - tricyclic antidepressants - some antimicrobials (saquinavir, sparfloxacin, erythromycin IV, pentamidine, antimalarials, in particular halofantrine) - some antihistamines (terfenadine, astemizole, mizolastine) - others (cisapride, vincamine IV c, bepridil, difemanil). Moxifloxacin should be used with caution in patients taking drugs that reduce potassium levels (eg, loop and thiazide diuretics, laxatives, enemas (high doses), corticosteroids, amphotericin B) or drugs associated with clinically significant bradycardia. The interval between taking drugs containing divalent or trivalent cations (for example, antacids containing magnesium or aluminum, didanosine tablets, sucralfate and drugs containing iron or zinc) and moxifloxacin should be about 6 hours. Activated charcoal Concomitant use of activated charcoal when taking oral moxifloxacin at a dose of 400 mg led to a marked decrease in absorption and a decrease in systemic bioavailability of the drug by more than 80%. The simultaneous use of these two drugs is not recommended (except in cases of overdose). Digoxin When repeated doses of moxifloxacin were administered to healthy volunteers, the maximum concentration (Cmax) of digoxin increased by approximately 30%, while the area under the concentration-time curve (AUC) and the minimum concentration (Cmin) of digoxin did not change. The results of studies conducted on volunteers with diabetes mellitus showed that with simultaneous oral administration of moxifloxacin and glibenclamide, the concentration of glibenclamide in the blood plasma decreased by approximately 21%, which theoretically could lead to the development of a mild form of transient hyperglycemia. However, the observed pharmacokinetic changes did not lead to changes in pharmacodynamic parameters (blood glucose, insulin). Change in INR value (international normalized ratio) In patients receiving anticoagulants in combination with antibacterial agents (especially fluoroquinolones, macrolides, tetracyclines, cotrimoxazole and some cephalosporins), there have been cases of increased anticoagulant activity of anticoagulants. Risk factors are the presence of an infectious disease (and concomitant inflammatory process), age and general condition of the patient. Therefore, it is difficult to assess whether infection or treatment is causing the INR abnormality. It is necessary to frequently monitor the INR and, if necessary, adjust the dose of oral anticoagulants. Clinical studies have shown no interaction with concomitant use of moxifloxacin and the following drugs: ranitidine, probenecid, oral contraceptives, calcium supplements, parenteral morphine, theophylline, cyclosporine or itraconazole. In vitro studies with human cytochrome P450 enzymes support these findings. Taking these results into account, it can be concluded that a metabolic interaction involving cytochrome P450 enzymes is unlikely. Food Interactions Moxifloxacin has no clinically significant interactions with food, including dairy products.
Pharmakinetics
After oral administration, moxifloxacin is absorbed quickly and almost completely. Absolute bioavailability is about 91%. After a single dose of 400 mg of moxifloxacin, the maximum concentration (Cmax) in the blood is reached within 0.5-4 hours and is 3.1 mg/l. Peak and trough plasma concentrations at steady state (400 mg once daily) were 3.2 and 0.6 mg/L, respectively. At steady state, drug exposure during the dosing interval is approximately 30% higher than after the first dose. Distribution Moxifloxacin is rapidly distributed in the extravascular space; after taking 400 mg of the drug, the area under the pharmacokinetic curve (AUC) is 35 mg/h/l. The equilibrium volume of distribution (Vss) is about 2 l/kg. In in vitro and in vivo studies, the binding of moxifloxacin to plasma proteins was 40-42%, regardless of drug concentration. Moxifloxacin is primarily bound to serum albumin. Metabolism Moxifloxacin undergoes stage II biotransformation and is excreted from the body through the kidneys and gastrointestinal tract unchanged, as well as in the form of a sulfo compound (M1) and a glucuronide (M2). These metabolites are applicable only to the human body and do not have antimicrobial activity. The study of metabolic pharmacokinetic interactions with other drugs showed that moxifloxacin is not biotransformed by the microsomal cytochrome P450 system. There are no indicators of oxidative metabolism. Elimination The half-life of the drug from plasma is approximately 12 hours. The average total clearance after administration of a dose of 400 mg ranges from 179 to 246 ml/min. Renal clearance, approximately 24-53 ml/min, occurs through partial tubular reabsorption of the drug in the kidneys. The combined use of ranitidine and probenecid does not affect the renal clearance of the drug. Regardless of the route of administration, the parent substance moxifloxacin is almost completely 96-98% metabolized to stage II metabolites without signs of oxidative metabolism. Pharmacokinetics in various patient groups Higher plasma concentrations of the drug were observed in healthy volunteers with low body weight (for example, women) and in elderly volunteers. The pharmacokinetic properties of moxifloxacin do not differ significantly in patients with renal failure (including those with creatinine clearance > 20 ml/min/1.73 m2). With a decrease in renal function, the concentration of the M2 metabolite (glucuronide) increases by a factor of 2.5 (with creatinine clearance
