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

Composition:Each film-coated tablet contains:
active substance: moxifloxacin hydrochloride 436.30 mg (corresponding to moxifloxacin - 400 mg)
Excipients: corn starch - 52 mg; sodium lauryl sulfate - 7.5 mg; talc purified - 15 mg; magnesium stearate - 6.5 mg; sodium carboxymethyl starch - 20 mg; silicon dioxide colloidal anhydrous - 3.5 mg; sodium croscarmellose - 6.5 mg; cellulose microcrystalline - 130.7 mg.
Shell: Opadry white (85G58977) Make-Colorcon (polyvinyl alcohol, titanium dioxide, talc, macrogol-3000, lecithin (soybean)) - 17.32 mg; iron oxide red -0.68 mg.

Description:Pinkish-red color, oval, biconcave, tablets with a risk, covered with a film membrane. In the fracture, a homogeneous mass from white to light yellow with a greenish tint of color.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A.14 Moxifloxacin

Pharmacodynamics:Moxifloxacin - bactericidal antibacterial preparation of broad spectrum of action of fluoroquinolone series, 8-methoxy fluoroquinolone.It inhibits topoisomerase II and topoisomerase IV, disrupts supercoiling and cross-linking of DEEC gaps, suppresses DNA synthesis, causes deep morphological changes in the cytoplasm, cell wall and membranes of sensitive microorganisms. The minimum bactericidal concentrations of moxifloxacin are generally comparable to its minimum inhibitory concentrations (MICs).
Mechanisms that lead to the development of resistance to penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines, do not interfere with the antibacterial activity of moxifloxacin. Cross-resistance between these groups of antibacterial drugs and moxifloxacin is not noted. So far, no cases of plasmid resistance have been observed. The overall frequency of development of resistance is very low (10^-⁷ - 10^-10) . Resistance to moxifloxacin develops slowly by multiple mutations. Multiple effects of moxifloxacin on microorganisms at concentrations below MIC are accompanied by only a slight increase in MIC. There are cases of cross-resistance to quinolones.Nevertheless, some gram-positive and anaerobic microorganisms resistant to other quinolones retain sensitivity to moxifloxacin.
Moxifloxacin in vitro is active against a wide range of gram-negative and gram-positive microorganisms, anaerobes, acid-fast bacteria and atypical bacteria such as Mycoplasma spp., Chlamydia spp., Legionella spp., And 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 strains resistant to penicillin and strains with multiple antibiotic resistance), Streptococcus pyogenes (group A) *, group Streptococcus milleri (S. cinginosus *, S. constellatus *, S. intermedius *) , group Streptococcus viridans (S. viridans, S. mutans, S. mitis, S. sanguinis, S. salivarius, S. thermophilus, S. constellatus), Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus aureus (including strains sensitive to methicillin) *, coagulase-negative staphylococci (S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans), including strains sensitive to methicillin.
Literature
Haemophillus influenzae (including strains producing and non-producing beta-lactamases) *, Haemophillus parainfluenzae *, Moraxella catarrhalis (including strains producing and non-producing beta-lactamases) *, Bordetella pertussis, Legionella pneumophila, Acinetobacter baumanii, 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 burnettii.
Moderately sensitive:
Gram-positive
Enterococcus faecalis * (strains sensitive to vancomycin and gentamicin only), Enterococcus avium *, Enterococcus faecium *.
Gram-negative
Escherichia coli *, Klebsiella pneumoniae *, Klebsiella oxytoca, Citrobacter freundii * Enterobacter spp. (E. aerogenes, E. intermedins, E. sakazakii), Enterobacter cloacae *, Pantoea agglomerans, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia, Proteus mirabilis * Morganella morganii, Neisseria gonorrhoeae *, Providencia spp. (P. rettgeri, P. stuartii).
Anaerobes
Bacteroides spp. (B. fragilis *, B. distasonis *, B. thetaiotaomicron * B. ovatus *, B. uniformis *, B. vulgaris *), Peptostreptococcus spp., Clostridium spp.
Resistant:
Gram-positive
Staphylococcus aureus (resistant to metizmillin / ofloxacin strains) +, coagulase-negative staphylococci (S. cohnii, S. epidermidis, S. haemolyticus, S. homnis, S. saprophyticus, S. simulans), methicillin-resistant strains.
Gram-negative
Pseudomonas aeruginosa
* - Sensitivity to moxifloxacin is confirmed by clinical data.
+ The use of Heinemox is not recommended for the treatment of infections caused by S. 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.

Pharmacokinetics:Suction: After oral administration moxifloxacin quickly and almost completely absorbed from the gastrointestinal tract (GIT). Food intake has little effect on the speed and completeness of absorption. Bioavailability - 91%. The maximum concentration of moxifloxacin in the blood plasma after ingestion at a dose of 400 mg is reached within 0.5-4hours and is equal to 3.1 mg / l.
Distribution: Moxifloxacin quickly distributed in tissues and organs. The connection with plasma proteins (mainly with albumins) is approximately 45%. The distribution volume is approximately 2 l / kg.
High concentrations of moxifloxacin, exceeding those in plasma, are reached in the lung tissue (including alveolar macrophages), in the bronchial mucosa, in the nasal sinuses, in exudate from the focus of skin inflammation. Also high concentrations of moxifloxacin are created in the tissues of the abdominal cavity, peritoneal fluid and female genital organs. In the interstitial fluid and in the saliva moxifloxacin is determined in a free, not protein-related form, at a concentration higher than in the blood plasma.
Metabolism: After passing the 2nd phase of biotransformation moxifloxacin is excreted from the body by the kidneys and the digestive tract both in an unchanged form, and in the form of inactive sulfo compounds and glucuronides. Moxifloxacin does not undergo biotransformation by the microsomal system of cytochrome P450.
Excretion: The half-life of moxifloxacin is approximately 12 hours. The average total clearance after taking 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% were found for AUC and C max. Absorption of moxifloxacin did not depend on sex. Differences in AUC and Cmax were due to differences in weight rather than sex and are not considered clinically significant. There were no clinically significant differences in the pharmacokinetics of moxifloxacin in patients of different ethnic groups and different sexes.
Children. The pharmacokinetics of moxifloxacin in children have not been studied.
Renal failure. 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.
Violation of the function of the liver. 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 (for use in patients with cirrhosis, see "Contraindications" ).

Indications:Infectious-inflammatory diseases caused by micro-organisms sensitive to moxifloxacin:
-hospital pneumonia, including community-acquired pneumonia, the causative agents of which are strains of microorganisms with multiple resistance to antibacterial drugs *;
-expansion of chronic bronchitis;
- Acute bacterial sinusitis;
- uncomplicated and complicated infections of the skin and soft tissues (including an infected diabetic foot);
-complicated intra-abdominal infections, including polymicrobial infections, including intraperitoneal abscesses;
- uncomplicated inflammatory diseases of the pelvic organs (including salpingitis and endometritis).
* Streptococcus pneumoniae with multiple antibiotic resistance include penicillin resistant strains and strains resistant to two or more antibiotics from groups such as penicillins (with MIC> 2 μg / ml), second generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim / sulfamethoxazole.

Contraindications:-increased sensitivity to moxifloxacin, other quinolones or other components of the drug;
-Children under 18 years of age;
-Allergic reactions to peanuts or soy;
- the damage of tendons during the previous treatment with quinolones;
- simultaneous reception of drugs that extend the QT interval (including antiarrhythmic drugs of class IA, III) - see the section "Interaction with other drugs"; application of moxifloxacin leads to an elongation of the QT interval. In this regard, the use of moxifloxacin is contraindicated in patients of the following categories:
Congenital or acquired documented QT interval extensions; 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;
patients with impaired 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;
- Pregnancy, lactation.

Carefully:- with diseases of the central nervous system (including suspicious for involvement of the central nervous system), predisposing to the occurrence of seizures and reducing the threshold of convulsive activity;
- in patients with psychoses and psychiatric illnesses in the anamnesis;
- in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia, especially in women and elderly patients;
- Myasthenia gravis;
- with cirrhosis of the liver;
- with simultaneous administration with drugs that reduce the content of potassium.

Dosing and Administration:Inside. The tablet is swallowed whole, without chewing, squeezed with enough water, regardless of the food intake (preferably after eating). Do not exceed the recommended dose.

Infection	Dose every 24 hours (1 time per day).	Duration of treatment, days
Community-acquired pneumonia	400 mg	7-14
With an exacerbation of chronic bronchitis	400 mg	5-10
Acute bacterial sinusitis	400 mg	7
Uncomplicated skin and soft tissue infections	400 mg	7
Complicated infections of the skin and subcutaneous structures	400 mg	7-21
Complicated intra-abdominal infections	400 mg	5-14
Uncomplicated pelvic inflammatory disease	400 mg	14

Do not exceed the recommended duration of treatment.
Do not change the dosage regimen:
- in elderly patients;
- in patients with impaired liver function (class A, B on the Child-Pugh scale);
- in patients with impaired renal function (incl.with severe renal failure with creatinine clearance <30 mL / min / 1.73 m2, as well as those on continuous hemodialysis and long-term outpatient peritoneal dialysis);
- in patients of different ethnic groups.

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.
From the digestive tract: often - nausea, vomiting, abdominal pain, diarrhea; infrequent - decreased appetite and reduced food intake, constipation, dyspepsia, flatulence, gastroenteritis (except erosive gastroenteritis), increased amylase activity; rarely - dysphagia. stomatitis, pseudomembranous colitis (in very rare cases associated with life-threatening complications).
From the liver and bile ducts: often - increased activity of "liver" transaminases; infrequent violations of liver function (including increased activity of lactate dehydrogenase level), increased bilirubin concentration, increased activity of gamma-glutamyltransferase and alkaline phosphatase; rarely-zheltuha, hepatitis (mostly cholestatic); very rarely - fulminant hepatitis,potentially leading to life-threatening liver failure.
From the cardiovascular system: often - prolongation of the QT interval (in patients with concomitant hypokalemia); infrequent - prolongation of QT interval, palpitation, tachycardia, vasodilation ("hot flushes" of blood to face); rarely -
ventricular tachyarrhythmias, fainting, increased blood pressure, lowering blood pressure; very rarely - nonspecific arrhythmias, polymorphic ventricular tachycardia (torsades des pointes), cardiac arrest (mainly in persons with predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia).

From the nervous system: often - headache, dizziness; infrequently, paresthesia / dysesthesia, impairment / loss of taste sensitivity, confusion, disorientation, sleep disorders, tremor, vertigo, drowsiness; (including anosmia), abnormal dreams, impaired coordination (including gait disturbances due to dizziness or vertigo, in very rare cases leading to trauma), seizures with various clinical manifestations (including "grand mal" seizures ), attention disorders, speech disorders, amnesia,peripheral neuropathy and polyneuropathy; very rarely hyperesthesia. Mental disorders: infrequent - feelings of anxiety, increased psychomotor activity / agitation; rarely - emotional lability, depression, hallucinations; very rarely - depersonalization, psychotic reactions (potentially manifested in behavior with a tendency to self-harm, including suicidal thoughts or suicidal attempts).

From the side of the organ of vision: infrequently - visual impairment (especially with reactions from the central nervous system); 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 organs of hematopoiesis and lymphatic system: infrequently - anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia, lengthening of prothrombin time / increase in international normalized ratio (INR); rarely - a change in the concentration of thromboplastin, very rarely - an increase in the concentration of prothrombin / decrease in INR.
From the respiratory system, chest and mediastinum: infrequently, shortness of breath (including asthmatic conditions).
From the musculoskeletal system: infrequently - arthralgia, myalgia; rare-tendinitis, increased muscle tone and cramps, muscle weakness; rarely -razryvy tendon, arthritis, abnormal gait due to damage to musculoskeletal system, increased symptoms of myasthenia gravis.
From the side of the kidneys and urinary tract: infrequently - dehydration (caused by diarrhea or decreased fluid intake); rarely - renal dysfunction, renal failure (due to dehydration, which may lead to kidney damage, especially in elderly patients with concomitant impairment of renal function).
From the skin and subcutaneous tissues: very rarely - bullous skin reactions, for example, Stevens-Johnson syndrome or toxic epidermal necrolysis.
From the immune system: infrequently - allergic reactions: itching, rash, hives, eosinophilia; rarely - anaphylactic / anaphylactoid reactions, angioneurotic edema, laryngeal edema including (a potentially life-threatening); very rarely - anaphylactic / anaphylactoid shock (potentially life threatening).
From the side of metabolism: infrequently - hyperlipidemia, rarely - hyperglycemia, hyperuricemia.
Superinfections: often - fungal superinfections.
General disorders: infrequent - general malaise, nonspecific pain, sweating; rarely - swelling.

Overdose:In case of an overdose, one should be guided by the clinical picture and carry out symptomatic maintenance therapy with ECG monitoring. The use of activated carbon immediately after oral administration of the drug can help prevent excessive systemic exposure to moxifloxacin in cases of overdose.

Interaction:There is no clinically significant interaction of moxifloxacin with atenolol, ranitidine, calcium-containing additives, theophylline, oral contraceptives, glibenclamide. itraconazole, digoxin, morphine, probenecid. Correction of the dosing regimen when combined with these drugs is not required.
Antiaid drugs, minerals and multivitamins
The simultaneous use of moxifloxacin and antacid preparations, minerals and multivitamins can disrupt the absorption of moxifloxacin, due to the formation of chelate complexes with polyvalent cations,contained in these preparations, and, consequently, to reduce the concentration of moxifloxacin in the blood plasma. In this regard, antacid, antiretroviral drugs (for example, didanosine) and other drugs containing magnesium, aluminum, sucralfate, iron, zinc, should be taken at least 4 hours before or 4 hours after ingestion of moxifloxacin.
Drugs that extend the QT interval
As moxifloxacin affects the prolongation of the QT interval, the combined use of moxifloxacin with the following drugs is contraindicated:
- antiarrhythmic IA (quinidine, hydroquinidine, disopyramide, etc.) and III (amiodarone, sotalol, dofetil, ibutilide, etc.) classes;
- Tricyclic antidepressants;
- Neuroleptics (phenothiazine, pimozide, sertindole, haloperidol, sultopride, etc.);
- antimicrobials (sparfloxacin, erythromycin IV, pentamidine, antimalarial drugs, especially halofantrine);
- antihistamines (astemizole, terfenadine, misolastine);
- others (cisapride, wincamine IV, bepridil, difemanyl).
Warfarin
When combined with warfarin, prothrombin time and other coagulation parameters 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 no interaction between moxifloxacin and warfarin has been detected, 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 do not significantly affect the pharmacokinetic parameters of each other. When repeated doses of moxifloxacin were used, the maximum digoxin concentration increased by approximately 30%, while the area under the concentration-time curve (AUC) and the minimum digoxin concentration did not change.
Activated carbon
With the simultaneous use of activated carbon and moxifloxacin inside at a dose of 400 mg, the systemic bioavailability of moxifloxacin is reduced by more than 80%.as a result of inhibition of its absorption.
Glucocorticosteroids
With the simultaneous use of moxifloxacin and glucocorticosteroids, the risk of tendonitis and rupture of tendons increases.

Special instructions:In some cases, after the first use of the drug may develop hypersensitivity and allergic reactions, which should immediately inform the doctor. Very rarely anaphylactic reactions can progress to a life-threatening anaphylactic shock even after the first use of the drug. In these cases, treatment with Heinemox should be canceled and necessary medical measures (including anti-shock) should be carried out.
When applying the Heinemox preparation, in some patients, the QT interval may be prolonged. The prolongation of the QT interval 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 QT interval. Therefore, do not exceed the recommended dose (400 mg / day). Elderly patients and women are more sensitive to drugs that extend the QT interval.When using the Heinemox preparation, the risk of developing ventricular arrhythmias in patients with predisposing arrhythmias may increase. In this regard, you can not use the drug Heinemox in the following cases: prolongation of the QT interval: 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 QT interval (including antiarrhythmic drugs of class IA, III), etc. (see "Interaction with other drugs").
When using the drug Heinemox, cases of fulminant hepatitis, potentially leading to the development of hepatic insufficiency, are noted. If you experience symptoms of liver dysfunction, you should consult your doctor before continuing with the drug.
When receiving the drug Heinemox, cases of development of bullous skin lesions (Stevens-Johnson syndrome or toxic epidermal necrolysis) were reported.The patient should be informed that in case of symptoms of skin or mucous membrane damage, the doctor should be consulted before continuing with the Heinemox preparation.
The use of drugs quinolone series is associated with a possible risk of seizures. The Heinemox preparation should be used with caution in patients with CNS diseases and with CNS disorders that predispose to seizures or reduce the threshold of seizure activity.
The drug Hymemox should be used with caution in patients with myasthenia gravis in connection with possible exacerbation of the disease.
The drug Hymemox should be used with caution in patients with a deficiency of glucose-6-phosphate dehydrogenase because of the possible development of hemolytic reactions.
The use of broad-spectrum antimicrobials, including Heinemox, is associated with a risk of developing pseudomembranous colitis. This diagnosis should be borne in mind in patients who have severe diarrhea on the background of treatment with Heinemox. 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.
Against the background of quinolone therapy, including moxifloxacin, tendonitis and tendon rupture are possible, especially in elderly patients and patients receiving glucocorticosteroids in parallel. When the first symptoms of pain or inflammation of the tendons should stop taking the drug 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 including. direct sunlight.
It is not recommended to use moxifloxacin for the treatment of infections caused by Staphylococcus aureus resistant to methicillin (MRSA). In the case of suspected or confirmed infections caused by MRSA, treatment should be prescribed with appropriate antibacterial drugs (see the section "Pharmacodynamics").
The ability of the Heinemox preparation to suppress the growth of mycobacteria can cause interaction of moxifloxacin in vitro with a test for Mycobacterium spp., Leading to false negative results in the analysis of samples of patients who undergo treatment with Heinemox during this period.
Patients undergoing quinolone treatment, including Heinemox, described cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia, or weakness. Patients undergoing treatment with Heinemox should be warned about the need to seek immediate medical attention before continuing treatment if there are signs of neuropathy that include pain, burning, tingling, numbness, or weakness (see "Side effect" section).
Reactions from the psyche may occur even after the first appointment 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 suicidal attempts (see the "Side effect" section). If patients develop such reactions, Hymenox should be discontinued and appropriate measures taken.
Because of the wide spread and growing incidence of infections caused by Neuriseria resistant to fluoroquinolones, gonorrhoeae, in the treatment of patients with inflammatory diseases of the pelvic organs, monotherapy with moxifloxacin should not be carried out.Except where the presence of N. Gonorrhoeae resistant to fluoroquinolones is excluded. If there is no way to exclude the presence of N. Gonorrhoeae resistant to fluoroquinolones, the question of supplementing empirical therapy with moxifloxacin with an appropriate antibiotic that is active against N. Gonorrhoeae (eg, cephalosporin) should be addressed.

Effect on the ability to drive transp. cf. and fur:Fluoroquinolones, including moxifloxacin, can disrupt the ability of patients to drive a car and engage in other potentially dangerous activities requiring increased attention and speed of psychomotor reactions, due to the effects on the central nervous system and visual impairment.

Form release / dosage:Tablets coated with a film coat of 400 mg.

Packaging:For 5, 7 or 10 tablets in a blister of Al / PVC / PVDC or a blister from Al / Al. For 1, 2 or 10 blisters with instructions for use in a pack of cardboard.
For hospitals: 100, 500 or 1000 tablets per package of PVC, package with instructions for use in a jar of high-density polyethylene.

Storage conditions:Store at a temperature not exceeding 25 ° C.
Keep out of the reach of children.

Shelf life:5 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002783

Date of registration:24.12.2014 / 20.07.2016

Expiration Date:24.12.2019

The owner of the registration certificate:Highgans Laboratories Pvt. Ltd.Highgans Laboratories Pvt. Ltd. India

Manufacturer: & nbsp

HIGLANCE LABORATORIES Pvt. Ltd. India

Representation: & nbspHAYGLANCE LABORATORY HAYGLANCE LABORATORY India

Information update date: & nbsp2016-08-21

Illustrated instructions

Instructions

Heinemox (Hinemox)