Moxetero

Moxetero

moxifloxacin

Manufacturer:

Hetero Labs

Distributor:

Medicell Pharma
Full Prescribing Info
Contents
Moxifloxacin hydrochloride.
Description
Each film-coated tablet contains: 436.330 mg of Moxifloxacin Hydrochloride Ph. Eur. eq. to 400 mg of Moxifloxacin.
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 C21H24FN3O4*HCl.
Moxifloxacin hydrochloride Tablets are available as film-coated tablets containing moxifloxacin hydrochloride (equivalent to 400 mg moxifloxacin).
Excipients/Inactive Ingredients: The inactive ingredients are 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.
Action
Pharmacotherapeutic Group: Quinolone antibacterials, fluoroquinolones. ATC Code: J01 MA 14.
Pharmacology:
Pharmacodynamics: Mechanism of action: Moxifloxacin is a 8-methoxy-fluoroquinolone antibiotic with a broad spectrum of activity and bactericidal action. Moxifloxacin has in vitro activity against a wide range of gram-positive and gram-negative organisms, anaerobes, acid-fast bacteria, and atypicals eg. Mycoplasma spp., Chlamydia spp. And Legionella spp.
Moxifloxacin is effective against β-lactam and macrolide resistant bacteria. Studies in animal models of infection have demonstrated the high in vivo activity.
Resistance: Resistance mechanisms which inactivate penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not interfere with the antibacterial activity of moxifloxacin. There is no cross resistance between moxifloxacin and these agents. Plasmid-mediated resistance has not been observed to date.
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, a mechanism of fluoroquinolone resistance. In vitro studies have demonstrated that resistance to moxifloxacin develops slowly by multiple step mutations. A very low overall frequency of resistance was demonstrated (10-7 - 10-10). Serial exposure of organisms to sub-MIC concentrations of moxifloxacin showed only a small increase in MIC values.
Cross resistance among quinolones has been observed. However, some gram-positive and anaerobic organisms resistant to other quinolones are susceptible to moxifloxacin.
Effect on the intestinal flora in humans: In two volunteer studies, the following changes in the intestinal flora were seen following oral dosing with moxifloxacin. E. coli, Bacillus spp., Bacteroides vulgatus, Enterococci, and Klebsiella spp. were reduced, as were the anaerobes Bifidobacterium, Eubacterium, and Peptostreptococcus. These changes returned to normal within two weeks. Clostridium difficile toxin was not found. Moxifloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the Indications/Uses. (See Tables 1 and 2.)

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The frequency of acquired resistance may vary geographically and with time for certain species. Local area information on resistance of organisms is desirable, particularly when treating severe infections. The previously mentioned information is provided as a guide on the probability of an organism being susceptible to moxifloxacin.
Comparison of PK/PD surrogates for intravenous and oral administration of a 400 mg Moxifloxacin single dose In patients requiring hospitalisation AUC/MIC90 parameters greater than 125 and Cmax/MIC90 of 8 - 10 is predictive for clinical cure (Schentag). In outpatients these surrogate parameters are generally smaller, i.e. AUC/MIC90 greater than 30-40 (Dudley and Ambrose).
The following table provides the respective PK/PD surrogates for intravenous and oral administration of 400 mg moxifloxacin calculated from single dose data: (See Table 3.)

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Pharmacokinetics: Absorption and bioavailability: Following oral administration moxifloxacin is absorbed rapidly and almost completely. The absolute bioavailability amounts to approx. 91%". Pharmacokinetics are linear in the range of 50 - 1200 mg single dose and up to 600 mg once daily dosing over 10 days. Steady state is reached within 3 days. Following a 400 mg oral dose peak concentrations of 3.1 mg/l are reached within 0.5 - 4 hours post application. Peak and trough plasma concentrations at steady state (400 mg once daily) were 3.2 and 0.6 mg/l, respectively.
Concomitant administration of moxifloxacin together with food slightly prolongs the time to reach peak concentrations by approximately 2 hours and slightly reduced peak concentrations by approximately 16%. Extent of absorption remained unchanged. As AUC/MIC is most predictive for antimicrobial efficacy of quinolones, this effect is clinically not relevant. Therefore, Moxifloxacin can be administered independently from meals. After a single 400 mg intravenous 1 hour infusion peak concentrations of approximately 4.1 mg/L were reached in the plasma at the end of infusion which corresponds to a mean increase of approx. 26 % relative to the oral application. Exposure to drug in terms of AUC at a value of approximately 39 mg*h/L is only slightly higher compared to the exposure after oral administration (35 mg*h/L) in accordance with the absolute bioavailability of approximately 91%.
Following multiple intravenous dosing (1hour infusion), peak and trough plasma concentrations at steady state (400 mg once daily) were between 4.1 to 5.9 and 0.43 to 0.84 mg/L respectively. At steady-state the exposure to drug within the dosing interval is approximately 30 % higher than after the first dose. In patients mean steady state concentrations of 4.4 mg/l were observed at the end of a 1 hour infusion.
Distribution: Moxifloxacin is distributed very rapidly to extravascular spaces. Exposure to drug in terms of AUC (AUCnorm = 6 kg*h/l) is high with a volume of distribution at steady state (Vss ) of approximately 2 L/kg. In saliva peak concentrations higher than those of plasma may be reached. In in vitro and ex-vivo experiments over a range of 0.02 to 2 mg/l a protein binding of approximately 45 % independent from the concentration of the drug was determined. Moxifloxacin is mainly bound to serum albumin. Due to this low value high free peak concentrations > 10 x MIC are observed.
Moxifloxacin reaches high concentrations in tissues like lung (epithelial fluid, alveolar macrophages, biotic tissue), the sinuses (maxillary and ethmoid sinus, nasal polypi) and inflamed lesions (cantharide blister fluid) where total concentrations exceeding those of the plasma concentrations are reached. High free drug concentrations are measured in interstitial body water (saliva, intramuscular, subcutaneous). In addition, high drug concentrations were detected in abdominal tissues and fluids and female genital tract. (See Tables 4 and 5.)

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The peak concentrations and site vs. plasma concentration ratios for various target tissues yielded comparable results for both modes of drug administration after a single dose of 400 mg moxifloxacin.
Metabolism: Moxifloxacin undergoes Phase II biotransformation and is excreted via renal and biliary/faecal pathways as unchanged drug as well as in form of a sulfo-compound (M1) and a glucuronide (M2). M1 and M2 are the only metabolites relevant in humans, both are microbiologically inactive. Neither in in vitro nor in clinical Phase I studies metabolic pharmacokinetic interactions with other drugs undergoing Phase I biotransformation involving Cytochrome P-450 enzymes were observed. Independent from the route of administration the metabolites M1 and M2 are found in the plasma at concentrations lower than the parent drug. Preclinical investigations adequately covered both metabolites thus excluding potential implications with respect to safety and tolerability.
Elimination: Moxifloxacin is eliminated from plasma with a mean terminal half-life of approximately 12 hours. The mean apparent total body clearance following a 400 mg dose ranges from 179 to 246 ml/min. Renal clearance amounted to about 24 - 53 ml/min suggesting partial tubular reabsorption of the drug from the kidneys. Concomitant administration of ranitidine and probenecid did not alter renal clearance of the drug (see table as follows). Mass balance of the mother compound and Phase II metabolites of moxifloxacin yielded an almost complete recovery of approximately 96-98% independent from the route of administration with no indication of oxidative metabolism. A detailed overview of the mass balance according to elimination pathways (renal vs non-renal, metabolic vs. non-metabolic) and mode of application is given in the table as follows. Recovery of a 400 mg single dose (arithmetric mean ± standard deviation (SD). (See Table 6.)

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Geriatric patients: Pharmacokinetics of moxifloxacin are not affected by age.
Gender: There was a 33% difference in the pharmacokinetics (AUC, Cmax) of moxifloxacin between male and female subjects. Drug absorption was unaffected by gender. These differences in the AUC and Cmax were attributable to the differences in body weight rather than gender. They are not considered as clinically relevant.
Ethnic differences: Possible interethnic differences were examined in Caucasian, Japanese, Black and other ethnic groups. No clinically relevant interethnic differences in pharmacokinetics could be detected.
Children and adolescents: Pharmacokinetics of moxifloxacin were not studied in paediatric patients.
Patients with renal impairment: The pharmacokinetics of moxifloxacin are not significantly changed by renal impairment (including creatinine clearance < 30 ml/min/1.73m2) and in patients on chronic dialysis i. e. hemodialysis and continuous ambulatory peritoneal dialysis.
Patients with hepatic impairment: Moxifloxacin plasma concentrations of patients with mild to severe hepatic impairment (Child Pugh A to C) did not reveal clinically relevant differences compared to healthy volunteers or patients with normal hepatic function, respectively. There is no experience in patients with severe hepatic impairment (Child Pugh C).
Toxicology: Preclinical Safety Data: In a local tolerability study performed in dogs, no signs of local intolerability were seen when moxifloxacin was administered intravenously. After intra-arterial injection inflammatory changes involving the peri-arterial soft tissue were observed suggesting that intra-arterial administration of moxifloxacin should be avoided.
Carcinogenicity, Mutagenicity: Moxifloxacin, like other quinolones, was genotoxic in vitro tests using bacteria or mammalian cells. Since these effects can be explained by an interaction with the gyrase in bacteria and -at higher concentrations by an interaction with the topoisomerase II in mammalian cells, a threshold concentration for genotoxicity can be assumed. In in-vivo tests, no evidence of genotoxicity was found despite the fact that very high moxifloxacin doses were used. Thus, a sufficient margin of safety to the therapeutic dose in man can be provided. Moxifloxacin was non-carcinogenic in an initiation-promotion study in rats.
ECG: At high concentrations, moxifloxacin is an inhibitor of the delayed rectifier potassium current of the heart and may thus cause prolongations of the QT-interval. Toxicological studies performed in dogs using oral doses of ≥90 mg/kg leading to plasma concentrations ≥16 mg/l caused QT-prolongations, but no arrhythmias. Only after very high cumulative intravenous administration of more than 50 fold the human dose (> 300 mg/kg), leading to plasma concentrations of ≥200 mg/l (more than 30 fold the therapeutic level after intravenous administration), reversible, non-fatal ventricular arrhythmias were seen.
Arthrotoxicity: Quinolones are known to cause lesions in the cartilage of the major diarthodial joints in immature animals. The lowest oral dose of moxifloxacin causing joint toxicity in juvenile dogs was four times maximum recommended therapeutic dose (400 mg/50 kg person) on a mg/kg basis, with plasma concentrations two to three times higher than those at the recommended therapeutic dose.
Reprotoxicity: Reproductive studies performed in rats, rabbits and monkeys indicate that placental transfer of moxifloxacin occurs. Studies in rats (per os and i.v.) and monkeys (per os) did not show evidence of teratogenicity or impairment of fertility following administration of moxifloxacin. Skeletal malformations were observed in rabbits that had been treated with an intravenous dose of 20 mg/kg. This study result is consistent with the known effects of quinolones on skeletal development (see Use in Pregnancy & Lactation). There was an increase in the incidence of abortions in monkeys and rabbits at human therapeutic concentrations. In rats, decreased foetal weights, an increased prenatal loss, a slightly increased duration of pregnancy and an increased spontaneous activity of some male and female offspring was observed at doses which were 63 times the maximum recommended dose on a mg/kg basis with plasma concentrations in the range of the human therapeutic dose.
Indications/Uses
Moxifloxacin 400 mg film-coated tablets are indicated for the treatment of the following bacterial infections caused by susceptible strains: Respiratory tract infections: Acute Bacterial Sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.
Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Staphylococcus aureus, or Moraxella catarrhalis.
Community Acquired Pneumonia (of mild to moderate severity) caused by Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Moraxella catarrhalis.
Uncomplicated skin and skin structure infections caused by Staphylococcus aureus or Streptococcus pyogenes.
Complicated skin and skin structure infections caused by methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Enterobactercioacae.
Mild to moderate pelvic inflammatory disease (i.e. infections of female upper genital tract, including salpingitis and endometritis), without an associated tubo-ovarian or pelvic abscess.
Moxifloxacin 400 mg film-coated tablets are not recommended for use in monotherapy of mild to moderate pelvic inflammatory disease but should be given in combination with another appropriate antibacterial agent (eg. a cephalosporin) due to increasing moxifloxacin resistance of Neisseria gonorrhoeae.
Moxifloxacin 400 mg film-coated tablets are indicated for the treatment of the previously mentioned infections if they are caused by bacteria susceptible to moxifloxacin. For a full list of susceptible strains, please refer to Pharmacology: Pharmacodynamics under Actions.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Dosage/Direction for Use
Method of administration: Film-coated tablet: The film-coated tablet should be swallowed whole with sufficient liquid and may be taken independent of meals.
Dosage Regimen: Dose (adults): The recommended dose for Moxifloxacin is 400 mg once daily (1 film coated tablet) for the previously mentioned indications and should not be exceeded.
For complicated skin and skin structure infections, therapy should usually be initiated with intravenous formulation. When switching from intravenous to oral dosage administration, no dosage adjustment is necessary. Patients whose therapy is started with Moxifloxacin I.V. may be switched to Moxifloxacin Tablets when clinically indicated at the discretion of the physician.
Duration of treatment: The duration of treatment should be determined by the severity of the indication or clinical response. The following general recommendations are made: Acute exacerbation of chronic bronchitis, 5 days.
Acute sinusitis, 7 days.
Uncomplicated skin and skin structure infections, 7 days.
Community acquired pneumonia (mild to moderate in severity) 10 days.
Community acquired pneumonia: total recommended duration for sequential administration (intravenous followed by oral therapy) is 7-14 days.
Complicated skin and skin structure infections: total treatment duration for sequential therapy (intravenous followed by oral therapy) is 7-21 days.
Mild to moderate pelvic inflammatory disease, 14 days.
The recommended duration of treatment for the indication being treated should not be exceeded.
Moxifloxacin 400 mg film-coated tablets and Moxifloxacin 400 mg solution for infusion have been studied in clinical trials for up to 21 days (in complicated skin and skin structure infections).
Additional information on special populations: Children and adolescents: Efficacy and safety of Moxifloxacin in children and adolescents have not been established.
Geriatric patients: No adjustment of dosage is required in elderly.
Ethnic differences: No adjustment of dosage is required in ethnic groups.
Patients with hepatic impairment: No dosage adjustment is required in patients with mild or moderate impaired liver function. The use of moxifloxacin is not recommended in patients with severe hepatic impairment (Child Pugh C).
Patients with renal impairment: No dose adjustment is required in patients with any degree of renal impairment (including creatinine clearance ≤30 mL/min/1.73m2) and in patients on chronic dialysis i.e. hemodialysis and continuous ambulatory peritoneal dialysis.
Overdosage
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.
Contraindications
Hypersensitivity to moxifloxacin, other quinolones or to any of the excipients.
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 >5fold ULN.
Special Precautions
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 (incl. 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.
The benefit of moxifloxacin treatment especially in infections with a low degree of severity should be balanced with the information contained in the precautions section.
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 axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones, including Moxifloxacin. Symptoms may occur soon after initiation of Moxifloxacin and may be irreversible. Moxifloxacin should be discontinued immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation.
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-endangering 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.
Fluoroquinolones, including moxifloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Post-marketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid moxifloxacin in patients with a known history of myasthenia gravis.
Tendon inflammation, tendon rupture: Tendon inflammation and rupture may occur with quinolone therapy including moxifloxacin, particularly 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. Tendon inflammation and rupture may occur even up to several months after discontinuing quinolone therapy including moxifloxacin.
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 in patients. However, in specially designed preclinical and clinical studies photosensitivity has not been observed with Moxifloxacin. In addition, since first marketed there has been no clinical evidence that Moxifloxacin causes photosensitivity reactions. Nevertheless patients should be advised to avoid extensive exposure to either UV irradiation or sunlight. If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.
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 Moxifloxacin hydrochloride 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.
Interference with biological tests: Moxifloxacin in vitro activity may interfere with the Mycobacterium spp. culture test by suppression of mycobacterial growth, causing false negative results in specimens from patients currently taking 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.
Paediatric population: Due to adverse effects on the cartilage in juvenile animals the use of moxifloxacin in children and adolescents < 18 years is contraindicated.
Dysglycemia: As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with Moxifloxacin. In Moxifloxacin-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g. sulfonylurea) or with insulin. In diabetic patients, careful monitoring of blood glucose is recommended.
Drugs inhibiting peristalsis are contraindicated in patients who develop serious diarrhoea.
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 Pregnancy & Lactation
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 small amounts of moxifloxacin passes into milk. There is no data available in lactating or nursing women.
Side Effects
Adverse drug reactions (ADRs) based on all clinical studies with moxifloxacin 400 mg (oral and sequential [IV/oral]/intravenous only administration) sorted by CIOMS III categories of frequency (overall n= 17,951, including n = 4,583 from sequential/intravenous therapy studies; status: May 2010) are listed as follows: ADRs listed under "common" were observed with a frequency below 3% with the exception of nausea and diarrhea.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as: common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000). (See Table 7.)

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The following undesirable effects have a higher frequency in the subgroup of IV/oral sequentially treated patients: Common: Increased gamma-glutamyl-transferase.
Uncommon: Ventricular tachyarrhythmias, Hypotension, Edema, Antibiotic associated colitis (in very rare cases associated with life threatening complications), Seizures of various clinical manifestations (incl. grand mal convulsions), Hallucination, Renal impairment and renal failure (due to dehydration esp. in elderly with pre- existing renal disorders).
There have been very rare cases of the following side effects reported following treatment with other fluoroquinolones, which might possibly also occur during treatment with moxifloxacin: hypernatraemia, hypercalcaemia, haemolytic anaemia, rhabdomyolysis, photosensitivity reactions.
Drug Interactions
For the following substances absence of a clinically relevant interaction with Moxifloxacin was proven: atenolol, ranitidine, calcium supplements, theophylline, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid. No dose adjustment is necessary for these drugs.
Antacids, minerals and multi-vitamins: Concomitant ingestion of Moxifloxacin together with antacids, minerals and multi-vitamins may result in impaired absorption of the drug due to formation of chelate complexes with the multi-valent cations contained in these preparations. This may lead to plasma concentrations considerably lower than desired. Hence, antacids, anti-retroviral drugs and other preparations containing magnesium or aluminium, sucralfate and agents containing iron or zinc should be administered at least 4 hours before or 2 hours after ingestion of an oral moxifloxacin dose.
Warfarin: No interaction during concomitant treatment with warfarin on prothrombin time and other coagulation parameters has been observed.
Changes in INR (International Normalized Ratio): Cases of increased anticoagulant activity have been reported in patients receiving anticoagulants concurrently with antibiotics, including Moxifloxacin. The infectious disease (and its accompanying inflammatory process), age and general status of the patient are risk factors. Although an interaction between Moxifloxacin and warfarin was not demonstrated in clinical trials, INR monitoring should be performed and, if necessary, the oral anticoagulant dosage should be adjusted as appropriate.
Digoxin: The pharmacokinetics of digoxin are not significantly influenced by moxifloxacin and vice versa. After repeated dosing in healthy volunteers moxifloxacin increased Cmax of digoxin by approximately 30 % at steady state without affecting AUC or trough levels.
Charcoal: Concomitant dosing of charcoal and 400 mg oral Moxifloxacin reduced the systemic availability of the drug by more than 80 % by preventing absorption in vivo. The application of activated charcoal in the early absorption phase prevents further increase of systemic exposure in cases of overdose. After intravenous drug administration carbo medicinalis only slightly reduces systemic exposure (approx. 20%).
Food and dairy products: Absorption of moxifloxacin was not altered by food intake (including dairy products). Therefore, Moxifloxacin can be taken independent from food intake. An additive effect on QT interval prolongation of moxifloxacin and other medicinal products that may prolong the QTc interval cannot be excluded. This might lead to an increased risk of ventricular arrhythmias, including torsade de pointes. Therefore co-administration of moxifloxacin with any of the following medicinal products is contraindicated: anti-arrhythmics class IA (eg. Quinidine, hydroquinone, disopyramide); anti-arrhythmics class III (e.g. amiodarone, sotalol,dofetilide, ibutilide); antipsychotics (e.g phenothiazines, pimozide, sertindole, haloperidol, sultopride); tricyclic antidepressive agents; certain antimicrobial agents (sparfloxacin, erythromycin IV, pentamidine, antimalarials particularly halofantrine); certain antihistaminics (terfenadine, astemizole, mizolastine); others (cisapride, vincamine IV, bepridil, diphemanil).
Storage
Store below 30°C and protect from moisture.
MIMS Class
ATC Classification
J01MA14 - moxifloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
Presentation/Packing
FC tab 400 mg (pink coloured, capsule shaped, biconvex, debossed with '80' on one side and 'l' on the other side) x 3 x 10's, 10 x 10's.
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