Moxetero

Each film coated tablet contains Moxifloxacin 400 mg.
Moxifloxacin hydrochloride is a synthetic broad spectrum antibacterial agent for oral and intravenous administration. Moxifloxacin, a fluoroquinolone, is available as the monohydrochloride salt of 1-cyclopropyl-7-[(S,S)2,8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-1,4- dihydro-4-oxo-3 quinoline carboxylic acid. It is a slightly yellow to yellow crystalline substance with a molecular weight of 437.9. Its empirical formula is CHFNO*HC.
Excipients/Inactive Ingredients: Cellulose microcrystalline (Avicel PH 101), Croscarmellose sodium (Ac-Di-sol), Silica, colloidal anhydrous (Aerosil-200), Povidone K-30 (Kollidon-30), Purified water, Magnesium stearate and Opadry pink 03B34285.

Pharmacology: Pharmacodynamics: Mechanism of action: Moxifloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative pathogens.
The bactericidal action of moxifloxacin results from the inhibition of both type II topoisomerases (DNA gyrase and topoisomerase IV) required for bacterial DNA replication, transcription and repair. It appears that the C8-methoxy moiety contributes to enhanced activity and lower selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety. The presence of the bulky bicycloamine substituent at the C-7 position prevents active efflux, associated with the norA or pmrA genes seen in certain Gram-positive bacteria.
Pharmacodynamic investigations have demonstrated that moxifloxacin exhibits a concentration dependent killing rate. Minimum bactericidal concentrations (MBC) were found to be in the range of the minimum inhibitory concentrations (MIC).
Effect on the intestinal flora in humans: The following changes in the intestinal flora were seen in volunteers following oral administration of moxifloxacin: Escherichia coli, Bacillus spp., Enterococcus spp., and Klebsiella spp. were reduced, as were the anaerobes Bacteroides vulgatus, Bifidobacterium spp., Eubacterium spp., and Peptostreptococcus spp. For Bacteroides fragilis there was an increase. These changes returned to normal within two weeks.
Mechanism of resistance: Resistance mechanisms that inactivate penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not interfere with the antibacterial activity of moxifloxacin. Other resistance mechanisms such as permeation barriers (common in Pseudomonas aeruginosa) and efflux mechanisms may also effect susceptibility to moxifloxacin.
In vitro resistance to moxifloxacin is acquired through a stepwise process by target site mutations in both type II topoisomerases, DNA gyrase and topoisomerase IV. Moxifloxacin is a poor substrate for active efflux mechanisms in Gram-positive organisms.
Cross-resistance is observed with other fluoroquinolones. However, as moxifloxacin inhibits both topoisomerase II and IV with similar activity in some Gram-positive bacteria, such bacteria may be resistant to other quinolones, but susceptible to moxifloxacin.
Breakpoints: EUCAST clinical MIC and disk diffusion breakpoints for moxifloxacin (01.01.2011): See Table 1.

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Microbiological Susceptibility: The prevalence of acquired resistance may vary geographically and with time for selected species and local information of resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought where the local prevalence of resistance is such that utility of the agent in at least some types of infections is questionable. (See table 2.)

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Pharmacokinetics: Moxifloxacin is readily absorbed from gastrointestinal track with an absolute bioavailability of about 90%. It is widely distributed throughout the body tissues and is about 50% bound to plasma proteins. Moxifloxacin has an elimination half-life of about 12 hours, allowing once-daily dosing. It is metabolised principally via sulfate and glucuronide conjugation and is excreted in the urine and the faeces as unchanged drug and as metabolites, the sulfate conjugate primarily in the faeces and the glucuronide exclusively in the urine.

For the treatment of susceptible infections including respiratory, skin and skin structure and intra-abdominal infections.

Moxifloxacin is a fluoroquinolone antibacterial given by mouth or by intravenous infusion over 60 minutes as the hydrochloride in the treatment of susceptible infections. Doses are expressed in terms of the base; the usual dose is 400 mg once daily.
Moxifloxacin hydrochloride is also given as 0.5% eye drops for the treatment of bacterial conjunctivitis.

No specific countermeasures after accidental overdose are recommended. General symptomatic therapy should be initiated. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Concomitant administration of charcoal with a dose of 400 mg oral moxifloxacin will reduce systemic availability of the drug by more than 80%. The use of charcoal early during absorption may be useful to prevent excessive increase in the systemic exposure to moxifloxacin in cases of oral overdose.

Hypersensitivity to moxifloxacin, other quinolones or to any of the excipients listed.
Pregnancy and lactation.
Patients below 18 years of age.
Patients with a history of tendon disease/disorder related to quinolone treatment.
Both in preclinical investigations and in humans, changes in cardiac electrophysiology have been observed following exposure to moxifloxacin, in the form of QT prolongation. For reasons of drug safety, moxifloxacin is therefore contraindicated in patients with: Congenital or documented acquired QT prolongation; Electrolyte disturbances, particularly in uncorrected hypokalaemia; Clinically relevant bradycardia; Clinically relevant heart failure with reduced left-ventricular ejection fraction; Previous history of symptomatic arrhythmias.
Moxifloxacin should not be used concurrently with other drugs that prolong the QT interval.
Due to limited clinical data, moxifloxacin is also contraindicated in patients with impaired liver function (Child Pugh C) and in patients with transaminases increase >5 fold ULN.

The benefit of moxifloxacin treatment especially in infections with a low degree of severity should be balanced with the information contained in the warnings and precautions section.
Prolongation of QTc interval and potentially QTc-prolongation-related clinical conditions: Moxifloxacin has been shown to prolong the QTc interval on the electrocardiogram in some patients. In the analysis of ECGs obtained in the clinical trial program, QTc prolongation with moxifloxacin was 6 msec ± 26 msec, 1.4% compared to baseline. As women tend to have a longer baseline QTc interval compared with men, they may be more sensitive to QTc-prolonging medications. Elderly patients may also be more susceptible to drug-associated effects on the QT interval.
Medication that can reduce potassium levels should be used with caution in patients receiving moxifloxacin.
Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients), such as acute myocardial ischaemia or QT prolongation as this may lead to an increased risk for ventricular arrhythmias (including torsade de pointes) and cardiac arrest. The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded.
If signs of cardiac arrhythmia occur during treatment with moxifloxacin, treatment should be stopped and an ECG should be performed.
Hypersensitivity/allergic reactions: Hypersensitivity and allergic reactions have been reported for fluoroquinolones including moxifloxacin after first administration. Anaphylactic reactions can progress to a life-threatening shock, even after the first administration. In these cases moxifloxacin should be discontinued and suitable treatment (e.g. treatment for shock) initiated.
Severe liver disorders: Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with moxifloxacin. Patients should be advised to contact their doctor prior to continuing treatment if signs and symptoms of fulminant hepatic disease develop such as rapidly developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy.
Liver function tests/investigations should be performed in cases where indications of liver dysfunction occur.
Serious bullous skin reactions: Cases of bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with moxifloxacin. Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.
Patients predisposed to seizures: Quinolones are known to trigger seizures. Use should be with caution in patients with CNS disorders or in the presence of other risk factors which may predispose to seizures or lower the seizure threshold. In case of seizures, treatment with moxifloxacin should be discontinued and appropriate measures instituted.
Peripheral neuropathy: Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoaesthesias, dysaesthesias, or weakness have been reported in patients receiving quinolones including moxifloxacin. Patients under treatment with moxifloxacin should be advised to inform their doctor prior to continuing treatment if symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop.
Psychiatric reactions: Psychiatric reactions may occur even after the first administration of quinolones, including moxifloxacin. In very rare cases depression or psychotic reactions have progressed to suicidal thoughts and self-injurious behaviour such as suicide attempts. In the event that the patient develops these reactions, moxifloxacin should be discontinued and appropriate measures instituted. Caution is recommended if moxifloxacin is to be used in psychotic patients or in patients with history of psychiatric disease.
Antibiotic-associated diarrhoea incl. colitis: Antibiotic-associated diarrhoea (AAD) and antibiotic-associated colitis (AAC), including pseudomembranous colitis and Clostridium difficile-associated diarrhoea, has been reported in association with the use of broad spectrum antibiotics including moxifloxacin and may range in severity from mild diarrhoea to fatal colitis. Therefore it is important to consider this diagnosis in patients who develop serious diarrhoea during or after the use of moxifloxacin. If AAD or AAC is suspected or confirmed, ongoing treatment with antibacterial agents, including moxifloxacin, should be discontinued and adequate therapeutic measures should be initiated immediately.
Furthermore, appropriate infection control measures should be undertaken to reduce the risk of transmission. Drugs inhibiting peristalsis are contraindicated in patients who develop serious diarrhoea.
Patients with myasthenia gravis: Moxifloxacin should be used with caution in patients with myasthenia gravis because the symptoms can be exacerbated.
Tendon inflammation, tendon rupture: Tendon inflammation and rupture (especially Achilles tendon), sometimes bilateral, may occur with quinolone therapy including moxifloxacin, even within 48 hours of starting treatment and have been reported up to several months after discontinuation of therapy. The risk of tendinitis and tendon rupture is increased in elderly patients and in those treated concurrently with corticosteroids. At the first sign of pain or inflammation, patients should discontinue treatment with moxifloxacin, rest the affected limb(s) and consult their doctor immediately in order to initiate appropriate treatment (e.g. immobilisation) for the affected tendon.
Patients with renal impairment: Elderly patients with renal disorders should use moxifloxacin with caution if they are unable to maintain adequate fluid intake, because dehydration may increase the risk of renal failure.
Vision disorders: If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.
Prevention of photosensitivity reactions: Quinolones have been shown to cause photosensitivity reactions in patients. However, studies have shown that moxifloxacin has a lower risk to induce photosensitivity. Nevertheless patients should be advised to avoid exposure to either UV irradiation or extensive and/or strong sunlight during treatment with moxifloxacin.
Patients with glucose-6-phosphate dehydrogenase deficiency: Patients with a family history of, or actual glucose-6-phosphate dehydrogenase deficiency are prone to haemolytic reactions when treated with quinolones. Therefore, moxifloxacin should be used with caution in these patients.
Patients with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Patients with pelvic inflammatory disease: For patients with complicated pelvic inflammatory disease (e.g. associated with a tubo-ovarian or pelvic abscess), for whom an intravenous treatment is considered necessary, treatment with Moxetero 400 mg film-coated tablets is not recommended.
Pelvic inflammatory disease may be caused by fluoroquinolone-resistant Neisseria gonorrhoeae. Therefore in such cases empirical moxifloxacin should be co-administered with another appropriate antibiotic (e.g. a cephalosporin) unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded. If clinical improvement is not achieved after 3 days of treatment, the therapy should be reconsidered.
Patients with special cSSSi: Clinical efficacy of intravenous moxifloxacin in the treatment of severe burn infections, fasciitis and diabetic foot infections with osteomyelitis has not been established.
Interference with biological tests: Moxifloxacin therapy may interfere with the Mycobacterium spp. culture test by suppression of mycobacterial growth causing false negative results in samples taken from patients currently receiving moxifloxacin.
Patients with MRSA infections: Moxifloxacin is not recommended for the treatment of MRSA infections. In case of a suspected or confirmed infection due to MRSA, treatment with an appropriate antibacterial agent should be started.
Effects on Ability to Drive and Use Machines: No studies on the effects of moxifloxacin on the ability to drive and use machines have been performed. However, fluoroquinolones including moxifloxacin may result in an impairment of the patient's ability to drive or operate machinery due to CNS reactions (e.g. dizziness; acute, transient loss of vision) or acute and short lasting loss of consciousness. Patients should be advised to see how they react to moxifloxacin before driving or operating machinery.
Use in Children: Due to adverse effects on the cartilage in juvenile animals the use of moxifloxacin in children and adolescents <18 years is contraindicated.

Pregnancy: The use of moxifloxacin during pregnancy is contraindicated. The safety of moxifloxacin in human pregnancy has not been evaluated. Reversible joint injuries are described in children receiving some quinolones, however this effect has not been reported as occurring on exposed foetuses. Animal studies have shown reproductive toxicity. The potential risk for humans is unknown.
Lactation: The use of moxifloxacin during breast feeding is contraindicated. As with other quinolones, moxifloxacin has been shown to cause lesions in the cartilage of the weight bearing joints of immature animals. Preclinical data indicate that moxifloxacin passes into milk.

Nausea, diarrhea, headache, and dizziness.

As moxifloxacin has been shown to prolong the QT interval, it should not be given to patients receiving class Ia antiarrhythmic drugs (such as quinidine and procainamide) or class III antiarrhythmics (such as amiodarone and sotalol). In addition, caution should be exercised when moxifloxacin is used with other drugs known to have this effect (such as the antihistamines astemizole and terfenadine, cisapride, erythromycin, pentamidine, phenothiazines, or tricyclic antidepressants).

Store at temperatures not exceeding 30°C and protect from moisture.

Quinolones

J01MA14 - moxifloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.

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