Rotomox - instructions for use, dose, side effects, contraindications

Composition:For 250 ml:
Active substance: Moxifloxacin hydrochloride 436.00 mg in terms of moxifloxacin 400.00 mg Excipients: Mannitol 12500.00 mg, disodium edetate 25.00 mg, sodium hydroxide q.s., hydrochloric acid q.s., water for injection up to 250.0 ml.
Per 1 ml:
Active substance: Moxifloxacin hydrochloride 1,744 mg in terms of moxifloxacin 1,600 mg Excipients: mannitol 50,000 mg, disodium edetate 0.100 mg, sodium hydroxide q.s., hydrochloric acid q.s., water for injection up to 1.0 ml.

Description:Transparent light yellow or yellow liquid.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone.

ATX: & nbsp

J.01.M.A.14 Moxifloxacin

Pharmacodynamics:Antibacterial drug of the group of fluoroquinolones. Has a bactericidal effect. The mechanism of action is due to the inhibition of bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, which leads to a disruption in the synthesis of DNA from the microbial cell.
In vitro, the drug is active against a wide range of gram-negative and gram-positive bacteria, anaerobic, acid-fast and atypical bacteria. Effective against bacteria resistant to beta-lactam and macrolide antibiotics.
To moxifloxacin are sensitive Gram-positive bacteria: Enterococcus faecalis, Staphylococcus aureus (including strains sensitive to methicillin), Streptococcus
anginosus, Streptococcus constellatus, Streptococcus pneumoniae (including strains resistant to penicillin and macrolides), Streptococcus pyogenes (group A);
gram-negative bacteria: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including strains producing and not producing beta-lactamase), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including strains producing beta-lactamase), Proteus mirabilis;
anaerobic bacteria: Bacteroides fragilis, Bacteroides thetaiotaomicronron, Clostridium perfringens, Peptostreptococcus spp .; also Chlamydia pneumoniae, Mycoplasma pneumoniae.
According to in vitro studies on moxifloxacin are also sensitive:
aerobic gram-positive bacteria: Staphylococcus epidermidis, Streptococcus agalactiae, Streptococcus spp. groups of viridans;
aerobic gram-negative bacteria: Citrobacter freundii, Klebsiella oxytoca, Legionella pneumophila;
anaerobic bacteria: Fusobacterium spp., Prevotella spp.
There is no cross-resistance with penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines. The overall incidence of resistance is low. In vitro studies have shown that resistance to moxifloxacin develops slowly as a result of a number of consecutive mutations. Between drugs from the group of fluoroquinolones develops cross-resistance. However, some Gram-positive and anaerobic microorganisms resistant to other fluoroquinolones are susceptible to moxifloxacin.

Pharmacokinetics:After a single infusion of moxifloxacin at a dose of 400 mg for 1 hour, the maximum drug concentration (Stach) is reached at the end of the infusion and is approximately 4 mg / L. Absolute bioavailability is approximately 91%. After multiple intravenous infusions of the drug at a dose of 400 mg for 1 hour, Cmax varies in the range from 4 mg / L to 6.0 mg / L. Moxifloxacin is rapidly distributed in tissues and organs and binds to blood proteins (mainly albumins) by about 45%. The distribution volume is approximately 2 l / kg. High concentrations of the drug, exceeding those in the plasma, are created in lung tissue (including in alveolar macrophages), bronchial mucosa, in the nasal sinuses, in the foci of inflammation (in the contents of blisters in the lesions of the skin). In the interstitial fluid and in saliva, the drug is determined in a free, non-protein-binding form at a concentration higher than in the plasma.
Moxifloxacin undergoes biotransformation of the 2nd phase and is excreted from the body by the kidneys, as well as the intestines both in unmodified form and in the form of inactive sulfo compounds and glucuronides. Moxifloxacin does not undergo biotransformation by the microsomal system of cytochrome P450.
The half-life of the drug is approximately 12 hours. The average total clearance after administration in a dose of 400 mg is from 179 to 246 ml / min. About 22% of a single dose (400 mg) is excreted unchanged by the kidneys, about 26% by the intestine. Pharmacokinetics in special clinical cases:
There were no significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function.
The concentration of moxifloxacin in patients with impaired liver function (class A and B according to the Child-Pugh classification) did not differ significantly from that in healthy volunteers or in patients with normal liver function.

Indications:Infectious-inflammatory diseases caused by micro-organisms sensitive to moxifloxacin:
- community-acquired pneumonia;
- complicated skin and soft tissue infections;
complicated intra-abdominal infections.

Contraindications:- hypersensitivity to moxifloxacin and quinolone drugs, excipients;
- Pregnancy;
- damage to the tendons during the previous treatment with quinolones;
- lactation period;
- Children and adolescence (up to 18 years);
- simultaneous reception of drugs that extend the QT interval (including antiarrhythmic drugs of class IA, III) - see the section "Interaction with other medicinal products;
- prolongation of QT interval: congenital or acquired;
- uncorrected hypokalemia;
- clinically significant bradycardia;
- Clinically significant heart failure with a reduced fraction of the left ventricular ejection;
- presence in the anamnesis of disturbances of the cardiac rhythm, accompanied by clinical symptoms;
- a violation of liver function (class C according to the Child-Pugh classification) and an increase in the activity of transaminases more than five times higher than the upper limit of the norm.

Carefully:Convulsive syndrome (in the anamnesis), diseases of the central nervous system, predisposing to occurrence of seizures and lowering the threshold of convulsive activity; in patients with psychoses and psychiatric illnesses in the anamnesis; in patients with acute myocardial ischemia; in women and elderly patients; myasthenia gravis; with cirrhosis of the liver; with the simultaneous administration of drugs that reduce the concentration of potassium; deficiency of glucose-6-phosphate dehydrogenase.

Dosing and Administration:The drug is administered intravenously in the form of infusion duration of at least 60 minutes. The recommended dosage regimen of moxifloxacin is 400 mg (250 ml solution for infusion) 1 time a day for any infections. Do not exceed the recommended dose.
Duration of therapy.
The duration of treatment is determined by the localization and severity of the infection, as well as clinical effect.
Community-acquired pneumonia: 7-14 days.
Complicated infections of the skin and subcutaneous structures: 7-21 days.
Complicated intra-abdominal infections: 5-14 days.
Do not exceed the recommended duration of treatment. In the presence of indications, it is possible to switch to taking moxifloxacin in a tablet dosage form.
Elderly patients
Changes in the dosing regimen in elderly patients are not required.
Violation of the function of the liver (class A and B according to the Child-Pugh classification)
Patients with impaired hepatic function are not required to change the dosage regimen.
Renal insufficiency
In patients with impaired renal function (including with creatinine clearance <30 ml / min), as well as in patients on continuous hemodialysis and long-term outpatient peritoneal dialysis, changes in the dosing regimen are not required.The preparation can be administered either undiluted or in combination with the following compatible solutions:
Water for injection 0.9%
solution of sodium chloride 5%
dextrose solution 10%
dextrose solution
Ringer's lactate solution
If the drug is used in conjunction with other drugs, then each drug should be administered separately.

Side effects:Allergic reactions: urticaria, rash, itching, anaphylactic / anaphylactoid reactions: angioedema, including facial edema, larynx (potentially life-threatening), Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactic shock.
From the digestive system: abdominal pain, nausea, vomiting, diarrhea, increased activity "liver" enzymes, bloating, constipation, anorexia, stomatitis, glossitis, dysphagia, transient effects on the liver, jaundice, gastroenteritis, pseudomembranous colitis, hepatitis (primarily cholestatic), fulminant hepatitis , potentially leading to life-threatening liver failure.
From the nervous system: headache, dizziness, vertigo, insomnia or drowsiness,pathological dreams, hallucinations, anxiety, increased muscle tone, impaired coordination of movements, tremor, increased psychomotor activity / agitation, amnesia, paresthesia, emotional lability, speech disorders, attention disturbance, convulsions, confusion and disorientation, depression (possibly behavior with a tendency to self-harm, including suicidal thoughts or suicidal attempts), depersonalization, psychotic reactions (potentially manifested in behavior with a tendency to self-harm, incl. with suicidal thoughts or suicidal attempts), hyperesthesia, attention disorders, sensory or sensorimotor peripheral neuropathy.
From the sense organs: visual impairment (blurred vision, decreased visual acuity, loss of vision), loss of taste sensitivity, tinnitus, hearing impairment (including deafness), impaired sense of smell (including anosmia).
From the cardiovascular system: prolongation of the QT interval (often in patients with concomitant hypokalemia), palpitations, tachycardia, increased and decreased blood pressure, chest pain, fainting,vasolidation (blood flushes to the face), ventricular tachyarrhythmias, polymorphic ventricular tachycardia, cardiac arrest (predominantly in persons with predisposing arrhythmias, 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, muscle weakness, arthritis, tendon ruptures, increased symptoms of myasthenia gravis.
From the genitourinary system: vaginal candidiasis, vaginitis, abdominal pain, dehydration, facial edema, peripheral edema, impaired renal function, renal failure.
Laboratory indicators: anemia, leukopenia, neutropenia, thrombocytopenia, leukocytosis, increased prothrombin time, increase / decrease in the international normalized ratio, eosinophilia, thrombocytosis, changes in thromboplastin and prothrombin concentrations, increased activity of gamma-glutamintransferase, lactate dehydrogenase, alkaline phosphatase, amylase, increased bilirubin concentration in blood plasma , hyperglycemia, hyperlipidemia, hyperuricemia.
Local reactions: edema, pain, inflammation at the injection site, phlebitis / thrombophlebitis. Other: candidiasis, general discomfort, asthenia, sweating.

Overdose:There are limited data on the overdose of moxifloxacin. In case of an overdose, one should be guided by the clinical picture and carry out symptomatic maintenance therapy with ECG monitoring.

Interaction:With the simultaneous use of moxifloxacin and glucocorticosteroids, the risk of developing tendovaginitis and rupture of the tendon increases.
No dosage regimen correction is required when combined with atenolol, ranitidine, calcium-containing additives, theophylline, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid.
Drugs that extend the QT interval
Consider the possible additive effect of prolonging the QT interval of moxifloxacin and other drugs that affect the prolongation of the QT interval. With the simultaneous use of moxifloxacin with these drugs, the risk of ventricular arrhythmia increases, including arrhythmia torsades des pointes.
Contraindicated simultaneous use of moxifloxacin with the following drugs:
- antiarrhythmic IA (quinidine, hydroquinidine, disopyramide, etc.) III (amiodarone, sotalol, dofetil, ibutilide, etc.) classes;
- Tricyclic antidepressants;
- Neuroleptics (phenothiazine, pimozide, sertindole, haloperidol, sultopride, etc.);
- antimicrobials (sparfloxacin, erythromycin, pentamidine, halofantrine and other antimalarial drugs);
- antihistamines (astemizole, terfenadine, misolastine);
- others (cisapride, wincamine IV, bepridil, difemanyl).
Warfarin
When combined with warfarin prothrombin time and other parameters of blood coagulation do not change. However, in patients receiving concomitant treatment with these drugs, it is necessary to monitor the INR (international standardized ratio) and, if necessary, adjust the dose of oral anticoagulants.
Digoxin
Moxifloxacin and digoxin does not significantly affect the pharmacokinetic parameters of each other. When repeated doses of moxifloxacin were used, the maximum digoxin concentration increased by approximately 30%, and the minimum digoxin concentration did not change.
Activated carbon
With intravenous administration of moxifloxacin with simultaneous oral administration of activated charcoal, the systemic bioavailability of the drug is slightly reduced (approximately 20%) due to adsorption of moxifloxacin in the lumen of the gastrointestinal tract during enterohepatic recirculation.
Incompatibility
Do not inject infusion solution moxifloxacin simultaneously with other solutions incompatible with it, which include:
10% solution of sodium chloride
20% solution of sodium chloride
4.2%, 8.4% solution of sodium bicarbonate.

Special instructions:With the use of moxifloxacin, allergic reactions can develop up to anaphylactic shock. In these cases, the use of moxifloxacin should be discontinued and appropriate medical measures taken.
During treatment with moxifloxacin, inflammation and rupture of the tendon can develop, especially in elderly patients and in patients receiving glucocorticosteroids in parallel. When the first symptoms of pain or inflammation of the tendons should stop the administration of moxifloxacin and immobilize the affected limb.There is a direct relationship between an increase in the concentration of moxifloxacin and an increase in the QT interval (risk of developing ventricular arrhythmias, including torsades des pointes). Therefore, the recommended dose (400 mg / day) and the infusion rate (at least 60 minutes) should not be exceeded. Elderly patients and women are more sensitive to drugs that extend the QT interval.
When moxifloxacin was used, cases of fulminant hepatitis, potentially leading to liver failure, were noted. If symptoms of liver dysfunction occur, such as rapidly growing asthenia, jaundice, darkening of the urine, you should consult a doctor.
The use of broad-spectrum antimicrobials, including moxifloxacin, is associated with a risk of developing pseudomembranous colitis. This diagnosis should be kept in mind in patients who have severe diarrhea with moxifloxacin. In this case, you should cancel the drug and prescribe the appropriate therapy. Drugs that inhibit the peristalsis of the intestine are contraindicated in the development of severe diarrhea.
The use of drugs quinolone series is associated with a possible risk of seizures.
Moxifloxacin should be used with caution in patients with myasthenia gravis due to possible exacerbation of the disease.
The drug does not have a photosensitizing effect, however, during the treatment with the drug, it is recommended to avoid ultraviolet irradiation including. direct sunlight.
It is not recommended to use moxifloxacin for the treatment of infections caused by Staphylococcus aureus strains resistant to methicillin (MRSA). In the case of suspected or confirmed infections caused by MRSA, treatment should be prescribed with appropriate antibacterial drugs.
When moxifloxacin is used, it is possible to obtain false-negative results in the test for the isolation of Mycobacterium tuberculosis.
In patients receiving fluoroquinolones, including moxifloxacin, sensory or sensorimotor peripheral neuropathy was noted. If the patient has symptoms of neuropathy (pain, burning, tingling, numbness or weakness), the use of moxifloxacin should be discontinued. This minimizes the possible risk of irreversible changes.
Reactions from the psyche may occur even after the first use of moxifloxacin.In very rare cases, depression or psychotic reactions progress to suicidal thoughts and behavior with a tendency to self-harm, including suicidal attempts. In case of occurrence of such reactions in patients, discontinue the drug administration and take the necessary measures.

Effect on the ability to drive transp. cf. and fur:The drug may interfere with the patient's ability to engage in potentially hazardous activities requiring increased attention and rapid psychomotor reactions.

Form release / dosage:Solution for infusions 1.6 mg / ml.

Packaging:250 ml per bottle of low density polyethylene with a lid of low density polyethylene. Each bottle is packed in a polypropylene bag and placed in a cardboard box along with instructions for use.

Storage conditions:In a dry, protected from light place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001438

Date of registration:17.01.2012 / 02.02.2016

Expiration Date:17.01.2017

The owner of the registration certificate:Rowecq LimitedRowecq Limited United Kingdom

Manufacturer: & nbsp

SCAN BIOTECH, Ltd. India

Representation: & nbspROUTEC LIMITEDROUTEC LIMITEDUnited Kingdom

Information update date: & nbsp2016-08-21

Illustrated instructions

Instructions

Rotomox (Rotomox)