Aquamox - instructions for use, doses, side effects, contraindications

Antimicrobial drug 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.

The spectrum of antibacterial activity of moxifloxacin includes the following microorganisms:

Sensitive

Gram-positive

Gardnerella vaginalis, Streptococcus pneumoniae (including penicillin-resistant strains and strains with multiple antibiotic resistance), and strains resistant to two or more antibiotics, such as penicillin (minimum inhibitory concentration (MIC)> 2 μg / ml), second-generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, trimethoprim / sulfamethoxazole) *, Streptococcus pyogenes (group A) *, Streptococcus milleri (Streptococcus angiosus *, Streptococcus constellatus *, Streptococcus intermedius *), Streptococcus spp. groups viridans (Streptococcus viridans, Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Streptococcus salivarius, Streptococcus thermophilus, Streptococcus constellatus), Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus aureus (methicillin-sensitive strains) *, coagulase-negative staphylococci (Staphylococcus cohnii (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Staphylococcus haemolyticus (methicillin-sensitive strains), Staphylococcus hominis (methicillin-sensitive strains), Staphylococcus saprophyticus (methicillin-sensitive strains), Staphylococcus simulans (methicillin-sensitive strains)).

Gram-negative

Haemophilus influenzae (including strains producing and non-producing beta-lactamases), Haemophilus parainfluenzae*, Moraxella catarrhalis (including strains producing and non-producing beta-lactamases), Bordetella pertussis, Acinetobacter baumannii, Proteus vulgaris.

Anaerobes

Fusobacterium spp., Porphyromonas spp., Prevotella spp., Propionibacterium spp.

Atypical

Chlamydia pneumoniae *, Chlamydia trachomatis* Mycoplasma pneumoniae *, Mycoplasma hominis, Mycoplasma genitalium, Legionella pneumophila *, Coxiella burnetii.

Moderately-sensitive:

Gram-positive

Enterococcus faecalis (only strains, sensitive to vancomycin and gentamycin)*, Enterococcus avium *, Enterococcus faecium *.

Gram-negative

Escherichia coli *, Klebsiella pneumoniae *, Klebsiella oxytoca, Citrobacter freundii *, Enterobacter spp. (Enterobacter aerogenes, Enterobacter intermedius, Enterobacter sakazakii), Enterobacter cloacae*, Pantoea agglomerans, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia, Proteus mirabilis *, Morganella morganii, Neisseria gonorrhoeae * Providencia spp. (Providencia rettgeri, Providencia stuartii).

Anaerobes

Bacteroides spp. (Bacteroides fragilis *, Bacteroides distasonis *, Bacteroides thetaiotaomicron *, Bacteroides vulgaris*, Bacteroides ovatus*, Bacteroides uniformis *), Peptostreptococcus spp. *, Clostridium spp.*

* - Sensitivity to moxifloxacin is confirmed by clinical data.

To moxifloxacin resistant following microorganisms:

Staphylococcus aureus (methicillin / ofloxacin resistant strains), coagulase-negative Staphylococcus spp. ((S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S.saprophyticus, S simulans)), methicillin-resistant strains, Pseudomonas aeruginosa.

Pharmacokinetics:

After a single infusion of moxifloxacin at a dose of 400 mg for 1 hour, the maximum concentration of the drug (C_mOh) is achieved 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 C_max 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 the lung tissue (incl.in alveolar macrophages), bronchial mucosa, in the nasal sinuses, in the foci of inflammation (in the contents of the blisters in the lesion 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 is 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 different patient groups

Age, gender and ethnicity

In the study of the pharmacokinetics of moxifloxacin in men and women, differences in 33% in terms of the area under the pharmacokinetic curve "concentration-time" (AUC) and C_mOh. Absorption of moxifloxacin did not depend on sex.

Differences in indicators AUC and C_mOh were due to the difference in weight rather than sex and are not clinically significant.

There were no clinically significant differences in the pharmacokinetics of moxifloxacin in patients of different ethnic groups and ages.

Children

The pharmacokinetics of moxifloxacin in children have not been studied.

Renal insufficiency

There were no significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function (including patients with creatinine clearance <30 mL / min / 1.73 m²) and in patients on continuous hemodialysis and long-term outpatient peritoneal dialysis.

Impaired liver function

The concentration of moxifloxacin in patients with impaired hepatic function (classes A, B on the Child-Pugh scale) did not differ significantly from that in healthy volunteers or in patients with normal liver function (for use in patients with cirrhosis, see also "Special instructions ").

Indications:

Infectious-inflammatory diseases caused by micro-organisms sensitive to moxifloxacin:

- Community-acquired pneumonia, including community-acquired pneumonia, whose pathogens are strains of microorganisms with multiple resistance to antibacterial drugs;

- complicated skin and soft tissue infections (including an infected diabetic foot);

- Complicated intra-abdominal infections, including polymicrobial infections, including intraperitoneal abscesses.

* Streptococcus pneumoniae with multidrug resistance, including strains resistant to penicillin, strains resistant to 2 or more antibacterial drugs from groups such as penicillins (with MIC> 2 μg / ml), cephalosporins 2 generationscefuroxime), macrolides, tetracyclines and trimethoprim / sulfamethoxazole. It is necessary to take into account the current official guidelines on the rules for the use of antibacterial drugs.

Contraindications:

- Hypersensitivity to moxifloxacin, components of the preparation and other preparations of the quinolone series;

- pregnancy;

- the period of breastfeeding;

- age to 18 years;

- the presence in the anamnesis of a pathology of tendons, developed as a result of treatment with preparations of the quinolone series;

- changes in the electrophysiological parameters of the heart, expressed in the lengthening of the interval QT: Congenital or acquired documented interval lengthening QT, electrolyte disorders, especially uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with a reduced fraction of the left ventricular ejection; presence in the anamnesis of rhythm disturbances, accompanied by clinical symptoms;

- use with other drugs that extend the interval QT (see the section "Interaction with other medicinal products");

- violations 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, due to the limited amount of clinical data

Carefully:

In diseases of the central nervous system (CNS) (including suspicious for involvement of the central nervous system), predisposing to the occurrence of seizures and reducing the threshold of seizure activity; in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia and cardiac arrest, especially in women and elderly patients; with myasthenia gravis gravis; with cirrhosis of the liver; with simultaneous intake of drugs that reduce the content of potassium; deficiency of glucose-6-phosphate dehydrogenase; in patients with psychoses and psychiatric illnesses in the anamnesis.

Dosing and Administration:

The drug is administered intravenously in the form of infusion duration of at least 60 minutes. Recommended dosage regimen of the drug Aquamox: 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. At the initial stages of treatment, the drug can be used

Aquamox, a solution for infusion, and then, if there are indications, moxifloxacin can be prescribed for oral administration in the form of tablets coated with a film membrane. 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. According to clinical studies, the duration of treatment with moxifloxacin, a solution for infusions, can reach 21 days.

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 hepatic dysfunction are not required to change the dosage regimen (for use in patients with cirrhosis see the section "Special instructions").

Renal insufficiency

In patients with impaired renal function (including 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.

Use in patients of different ethnic groups

Dosage regimen changes are not required.

The drug can be administered intravenously both in undiluted form and in combination with the following compatible solutions (using a T-shaped adapter):

Water for injections

A solution of sodium chloride 0.9%

A solution of dextrose 5%

A solution of dextrose 10%

A solution of dextrose 40%

Ringer's solution

Ringer Lactate Solution

If the drug is used in conjunction with other drugs, then each drug should be administered separately.

Side effects:

The following undesirable phenomena are indicated depending on the frequency of occurrence in accordance with the following gradation: often: from ≥1 / 100 to <1/10; infrequently: from ≥1 / 1000 to <1/100; rarely: from ≥1 / 10000 to <1/1000; very rarely: <1/10000, including individual messages.

Superinfections: often - fungal superinfections.

On the part of the organs of hematopoiesis and lymphatic system: infrequently - anemia, leukopenia, neutropenia, thrombocytopenia, thrombocytosis, prolongation of prothrombin time / increase in the international normalized ratio (INR); rarely - change in the concentration of thromboplastin; very rarely - an increase in the concentration of prothrombin / decrease INR.

From the immune system: infrequently - allergic reactions: urticaria, pruritus, rash, eosinophilia; rarely anaphylactic / anaphylactoid reactions, angioedema, including laryngeal edema (potentially life-threatening); very rarely - anaphylactic / anaphylactoid shock (including potentially life-threatening).

From the side of metabolism and nutrition: infrequently hyperlipidemia; rarely hyperglycemia, hyperuricemia; very rarely - hypoglycemia.

Mental disorders: infrequently - a sense of anxiety, psychomotor hyperactivity / agitation; rarely - emotional lability, depression (in very rare cases, behavior with a tendency to self-harm, including suicidal thoughts or suicidal attempts), hallucinations; very rarely - depersonalization, psychotic reactions (potentially manifested in behavior with a tendency to self-harm, incl.suicidal thoughts or suicide attempts).

From the nervous system: often - dizziness, headache; infrequently paresthesia / dysesthesia, a violation of taste sensitivity (including very rare cases of agevia), confusion, disorientation, sleep disorders, vertigo, tremor, drowsiness; rarely - hypoesthesia, impaired sense of smell (including anosmia), pathological dreams, impaired coordination (including gait disturbances due to dizziness or vertigo, very rarely leading to trauma from falling, especially in elderly patients), seizures with various clinical manifestations (including number of "grand mal"Seizures), attention disorders, speech disorders, amnesia, sensory or sensorimotor peripheral neuropathy; very rarely hyperesthesia.

From the side of the organ of vision: infrequent - visual impairment - fuzzy, reduced visual acuity, diplopia, especially in combination with reactions from the central nervous system (CNS); very rarely - transient loss of vision (especially against the background of reactions from the central nervous system).

From the side of the hearing organ and labyrinthine disorders: rarely - noise in the ears, hearing impairment, including deafness (usually reversible).

From the side of the cardiovascular system: often - lengthening the interval QT (in patients with concomitant hypokalemia); infrequent - lengthening of the interval QT, tachycardia, palpitation, vasodilation ("tides" of blood to the face); rarely - ventricular tachyarrhythmias, increase and decrease in blood pressure, fainting; very rarely - nonspecific arrhythmias (including extrasystole), polymorphic ventricular tachycardia (torsades des pointes), cardiac arrest (mainly in people with predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia).

From the respiratory system and the mediastinum: infrequently - shortness of breath (including asthmatic condition).

From the gastrointestinal tract: often - nausea, vomiting, abdominal pain, diarrhea; infrequent - decreased appetite and decreased food intake, constipation, dyspepsia, flatulence, gastroenteritis (except for erosive gastroenteritis), increased amylase activity; rarely - dysphagia, stomatitis, pseudomembranous colitis (in very rare cases associated with life-threatening complications).

From the liver and biliary tract: often - increased activity of "liver" transaminases; infrequent - increased bilirubin concentration, violations of liver function (including increased lactate dehydrogenase activity), increased activity of gamma-glutamyltransferase and alkaline phosphatase; rarely - jaundice, hepatitis (mostly cholestatic); very rarely - fulminant hepatitis, potentially leading to life-threatening hepatic insufficiency (including fatal cases).

From the skin and subcutaneous tissues: very rarely - bullous skin reactions, for example, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening).

From the side of the musculoskeletal system: infrequently - arthralgia, myalgia; rarely - tendonitis, increased muscle tone and cramps, muscle weakness; very rarely - tendon ruptures, arthritis, gait disturbance due to musculoskeletal system damage, increased myasthenia gravis symptoms gravis.

From the side of the kidneys and urinary tract: infrequently - dehydration (caused by diarrhea or decreased fluid intake); rarely - a violation of kidney function,renal failure (as a result of dehydration, which can lead to kidney damage, especially in elderly patients with concomitant renal dysfunction).

General disorders: infrequent - general malaise, nonspecific pain, sweating; rarely - swelling.

Local Reactions: edema, pain, inflammation at the injection site, phlebitis / thrombophlebitis.

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 adjustment is required when combined with atenolol, ranitidine, calcium-containing additives, theophylline, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid.

Warfarin

When combined with warfarin prothrombin time and other parameters of blood coagulation do not change.However, in patients who received anticoagulants in combination with antibiotics, including moxifloxacin, there have been cases of increased anticoagulant activity of anticoagulant drugs. Risk factors are the presence of an infectious disease (and concomitant inflammatory process), the age and general condition of the patient. Despite the fact that there is no interaction between moxifloxacin and warfarin, in patients receiving concomitant treatment with these drugs, it is necessary to monitor the value of INR and, if necessary, adjust the dose of indirect anticoagulants.

Digoxin

Moxifloxacin and digoxin does not significantly affect the pharmacokinetic parameters of each other. In appointing repeated doses of moxifloxacin, the maximum digoxin concentration increased by approximately 30%, and the minimum digoxin concentration did not change.

Activated carbon

With intravenous administration with simultaneous oral administration of activated charcoal, the systemic bioavailability of the drug is slightly reduced (by approximately 20%) due to adsorption of moxifloxacin in the lumen of the gastrointestinal tract inprocess of enterohepatic recirculation.

Preparations, extension intervals QT

It should be taken into account the possible additive effect of lengthening the interval QT moxifloxacin and other drugs that affect the lengthening of the interval QT. With the simultaneous use of moxifloxacin with these drugs, the risk of ventricular arrhythmia, 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 for intravenous administration, pentamidine, antimalarial drugs, especially halofantrine);

- antihistamines (astemizole, terfenadine, misolastine);

- others (cisapride, wincamine for intravenous administration, bepridil, difemanyl).

Incompatibility

Do not administer the infusion solution of Aquamox at the same time as other incompatible solutions, including:

A solution of sodium chloride 10%

A solution of sodium chloride 20%

A solution of sodium bicarbonate 4.2%

A solution of sodium hydrogen carbonate 8.4%

Special instructions:

In some cases, after the first use of the drug may develop hypersensitivity and allergic reactions. Very rarely anaphylactic reactions can progress to a life-threatening anaphylactic shock even after the first use of the drug. In these cases moxifloxacin it is necessary to cancel and conduct the necessary medical measures (including anti-shock).

With the use of moxifloxacin in some patients, lengthening of the interval QT. Interval lengthening QT is associated with an increased risk of developing ventricular arrhythmias, including polymorphic ventricular tachycardia. There is a direct relationship between an increase in the concentration of moxifloxacin and an increase in the interval QT. Therefore, the recommended dose and infusion rate (400 mg / day for 60 minutes) should not be exceeded. Elderly patients and women are more sensitive to drugs that extend the interval QT. With the use of moxifloxacin, the risk of developing ventricular arrhythmias in patients with predisposing arrhythmias may increase.In this regard, you can not use the drug in the following cases: lengthening the interval QT: congenital or acquired; unadjusted 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; simultaneous reception of drugs that extend the interval QT (see the section "Interaction with other medicinal products").

The drug should be used with caution in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia and cardiac arrest; in patients with cirrhosis of the liver (since this category of patients can not exclude the risk of developing an extension of the interval QT).

When moxifloxacin was used, cases of fulminant hepatitis, potentially leading to liver failure, were noted. The patient should be informed that if symptoms of liver dysfunction, such as rapidly growing asthenia, jaundice, darkening of the urine, should be addressed to the doctor before continuing treatment.

Reported cases of bullous skin lesions (Stevens-Johnson syndrome, toxic epidermal necrolysis). Patients should be informed that in case of the onset of symptoms of skin lesions or mucous membranes should consult a doctor before you continue treatment with moxifloxacin.

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 gravis in connection with a possible exacerbation of the disease.

Moxifloxacin should be used with caution in patients with the presence of deficiency of glucose-6-phosphate dehydrogenase because of the possible development of haemolytic reactions.

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.

During treatment with moxifloxacin, inflammation and rupture of the tendon can develop, especially in elderly patients and in patients receiving glucocorticosteroids simultaneously. Cases that occurred within a few months after the end of treatment are described. When the first symptoms of pain or inflammation of the tendons should stop the use of moxifloxacin and immobilize the affected limb.

Moxifloxacin does not have a photosensitizing effect; nevertheless, during the treatment with the drug it is recommended to avoid ultraviolet irradiation, incl. direct sunlight.

It is not recommended to use moxifloxacin for the treatment of infections caused by strains Staphylococcus aureus, resistant to methicillin (MRSA). In the case of suspected or confirmed infections caused by MRSA, should be prescribed treatment with appropriate antibacterial drugs.

When using moxifloxacin, it is possible to obtain false-negative results in the isolation test Mycobacterium tuberculosis.

In patients receiving fluoroquinolones, including moxifloxacin, sensory or sensorimotor peripheral neuropathy was noted.The patient should be informed that if symptoms of neuropathy (pain, burning, tingling, numbness or weakness) appear, the use of moxifloxacin should be discontinued and a doctor should be consulted. 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. If patients develop such reactions, stop using the drug and take the necessary measures.

Because of the wide spread and growing incidence of infections caused by fluoroquinolone-resistant Neisseria gonorrhoeae, in the treatment of patients with inflammatory diseases of the pelvic organs, monotherapy with moxifloxacin should not be carried out (if it is not possible to exclude the presence of moxifloxacin-resistant Neisseria gonorrhoeae). In the absence of clinical improvement after 3 days of treatment, therapy should be reviewed.

As in the case of other fluoroquinolones, the use of moxifloxacin showed a change in the concentration of glucose in the blood, including hypo- and hyperglycemia. Disglycemia occurred mainly in elderly patients with diabetes mellitus, receiving concomitant therapy with oral hypoglycemic drugs (eg, sulfonylureas) or insulin. When moxifloxacin is used in patients with diabetes mellitus, careful monitoring of the concentration of glucose in the blood

Due to the lack of sufficient clinical data, the use of the drug in patients with severe impairment of liver function (class C on the Child-Pugh scale) is contraindicated.

Patients who follow a diet with a low salt content (with heart failure, kidney failure, with nephrotic syndrome) should take into account that the infusion solution contains sodium chloride. The daily dose of sodium in the preparation is 34 mmol.

Effect on the ability to drive transp. cf. and fur:

Against the background of the use of moxifloxacin, the patient's ability to drive and engage in other potentially hazardous activities may be impaired,requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Solution for infusion, 1.6 mg / ml.

Packaging:

250 ml of the drug in a bottle of low density polyethylene, sealed with a cork of low density polyethylene.

One bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

In dry, dark place at a temperature of no higher than 25 ° C.

Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002633

Date of registration:22.09.2014 / 29.01.2016

Expiration Date:22.09.2019

The owner of the registration certificate:ARS, LLC ARS, LLC Russia

Manufacturer: & nbsp

AQUARIUS ENTERPRISES India

Representation: & nbspARS, LLCARS, LLC

Information update date: & nbsp24.06.2017

Illustrated instructions

Instructions

Aquamox (Aquamox)