Avelox

Avelox

moxifloxacin

Manufacturer:

Bayer HealthCare Pharma

Distributor:

DKSH
Full Prescribing Info
Contents
Moxifloxacin HCl.
Description
Each tablet contains moxifloxacin HCl 436.8 mg equivalent to moxifloxacin 400 mg. It also contains croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, hypromellose, macrogol 4000, titanium dioxide (E171) and ferric oxide (E172) as inactive constituents.
Action
Pharmacology: 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, Chlamydia and Legionella spp.
The bactericidal action results from the interference with topoisomerase II and IV. Topoisomerases are essential enzymes which control DNA topology and assist in DNA replication, repair and transcription.
Moxifloxacin exhibits concentration-dependent bactericidal killing. Minimum bactericidal concentrations are generally similar to minimum inhibitory concentrations (MIC). Moxifloxacin is effective against β-lactam-resistant 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 to 10-10). Serial exposure of organisms to sub-MIC concentration 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.
Pharmacokinetics: Absorption and Bioavailability: Following oral administration, moxifloxacin is absorbed rapidly and almost completely. The absolute bioavailability amounts to approximately 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 concentration of 3.1 mg/L are reached within 0.5 - 4 hrs p.a. 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 hrs 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 independent from meals.
After a single 400 mg 1-hr IV 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 approximately 26% relative to the oral application. Exposure to drug in terms of AUC at a value of approximately 39 mg·hr/L is only slightly higher compared to the exposure after oral administration (35 mg·hr/L) in accordance with the absolute bioavailability of approximately 91%.
Following multiple IV dosing (1-hr infusion), peak and trough plasma concentrations at steady-state (400 mg once daily) were between 4.1-5.9 and 0.43-0.84 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-hr infusion.
Distribution: Moxifloxacin is distributed very rapidly to extravascular spaces. Exposure to drug in terms of AUC (AUCnorm= 6 kg·hr/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 0.02-2 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 polyp) 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, IM, SC). In addition, high drug concentrations were detected in abdominal tissues and fluids and female genital tract.
The peak concentrations and site versus plasma concentration ratios for various target tissues yielded comparable results for both modes of drug administration after a single dose of moxifloxacin 400 mg.
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 (CYP450) 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 t½ of approximately 12 hrs. The mean apparent total body clearance following 400-mg dose ranges from 179-246 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.
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.
Elderly: 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.
Interethnic 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: Pharmacokinetics of moxifloxacin were not studied in paediatric patients.
Renal Impairment: The pharmacokinetics of moxifloxacin are not significantly changed by renal impairment (including creatinine clearance <30 mL/min/1.73 m2) and in patients on chronic dialysis ie, hemodialysis and continuous ambulatory peritoneal dialysis.
Liver 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 (see also Precautions).
Toxicology: Preclinical Safety Data: In a local tolerability study performed in dogs, no signs of local intolerability were seen when moxifloxacin was administered IV. 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: Although conventional long-term studies to determine the carcinogenic potential of moxifloxacin have not been performed, it has been subject to a range of in vitro and in vivo genotoxicity tests. In addition, an accelerated bioassay for human carcinogenesis (initiation/promotion assay) was performed in rats. Negative results were obtained in 4 strains of the Ames test in the HPRT mutation assay in Chinese hamster ovary cells and in the UDS assay in rat primary hepatocytes. As with other quinolones, the Ames test with TA 102 was positive and the in vitro test in the Chinese hamster v79 cells showed chromosomal abnormalities at high concentrations (300 mcg/mL). However, the in vivo micronucleus assay in the mouse was negative. An additional in vivo assay, the dominant lethal assay in the mouse, was negative as well. It is concluded that the negative in vivo results adequately reflect the in vivo situation in terms of genotoxicity. No evidence of carcinogenicity was found in an initiation/promotion assay 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 IV administration of >50-fold the human dose (>300 mg/kg), leading to plasma concentrations of ≥200 mg/L (>30-fold the therapeutic level after IV administration), reversible, nonfatal 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 4 times the maximum recommended therapeutic dose (400 mg/50 kg person) on a mg/kg basis with plasma concentrations 2-3 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 IV) 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 IV dose of 20 mg/kg. This study result is consistent with the known effects of quinolones on skeletal development. 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.
Microbiology: Effect on the Intestinal Flora in Humans: In 2 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 2 weeks. Clostridium difficile toxin was not found.
In Vitro Susceptibility Data: Gram-Positive Bacteria: Sensitive: Streptococcus pneumoniae including multi-drug resistant Streptococcus pneumoniae (MDRSP) strains, penicillin-resistant S. pneumoniae (PRSP) and strains resistant to ≥2 of the following antibiotics: Penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins (eg, cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole; Streptococcus pyogenes (group A)*, Streptococcus milleri, Streptococcus mitior, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus*, Streptococcus constellatus*, Staphylococcus aureus (including methicillin-sensitive strains)*, Staphylococcus cohnii, Staphylococcus epidermidis (including methicillin-sensitive strains), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Corynebacterium diphtheriae, Enterococcus faecalis* (vancomycin, gentamycin, susceptible strains only). Intermediate: Staphylococcus aureus (methicillin/ofloxacin resistant strains)+, Staphylococcus epidermidis (methicillin/ofloxacin resistant strains)+.
Gram-Negative Bacteria: Sensitive: Gardnerella vaginalis, Haemophilus influenzae (including β-lactamase negative and positive strains)*, Haemophilus parainfluenzae*, Moraxella catarrhalis (including β-lactamase negative and positive strains)*, Bordetella pertussis, Escherichia coli*, Klebsiella pneumoniae*, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae*, Enterobacter intermedius, Enterobacter sakazaki, Proteus mirabilis*, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii. Intermediate: Pseudomonas aeruginosa, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia, Neisseria gonorrhoea*.
Anaerobes: Sensitive: Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis*, Bacteroides ovatus, Bacteroides thetaiotamicron*, Bacteroides uniformis, Fusobacterium spp, Peptostreptococcus spp, Porphyromonas spp, Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus, Prevotella spp, Propionibacterium spp, Clostridium perfringens*, Clostridium ramosum.
Atypicals: Sensitive: Chlamydia pneumoniae*, Chlamydia trachomatis**, Mycoplasma pneumoniae*, Mycoplasma hominis, Mycoplasma genitalum, Legionella pneumophila*, Coxiella burnettii.
Note: */**Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications.
+Moxifloxacin showed in vitro activity with MIC values in the susceptible range in methicillin-resistant staphylococci expressing only the MecA gene. The use of moxifloxacin is not recommended if these strains are identified.
The frequency of acquired resistance may vary geographically and with time for certain species. However, for moxifloxacin, this has not been observed to date. 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 pharmacokinetic/pharmacodynamic surrogates for IV and oral administration of a moxifloxacin 400-mg single dose.
In patients requiring hospitalisation AUC/MIC90 parameters >125 and Cmax/MIC90 of 8-10 is predictive for clinical cure. In outpatients, these surrogate parameters are generally smaller ie, AUC/MIC90 >30-40.
The following table provides the respective pharmacokinetic/pharmacodynamic surrogates for IV and oral administration of moxifloxacin 400 mg calculated from single dose data. (See table.)

Click on icon to see table/diagram/image
Indications/Uses
Treatment of adults (≥18 years) with the following bacterial infections caused by susceptible strains:
Respiratory tract infections eg, acute exacerbations of chronic bronchitis; acute sinusitis; community-acquired pneumonia (CAP) including CAP caused by multidrug-resistant strains. Multidrug-resistant Streptococcus pneumoniae (MDRSP) includes isolates known as penicillin-resistant S. pneumoniae (PRSP) and strains resistant to ≥2 of the following antibiotics: Penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins (eg, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.
Uncomplicated skin and skin structure infections. Complicated skin and skin structure infections (including diabetic foot infections).
Uncomplicated pelvic inflammatory disease (ie, infections of female upper genital tract, including salpingitis and endometritis).
Complicated intra-abdominal infections including polymicrobial infections eg, abscesses.
Dosage/Direction for Use
Adults: Recommended Dose: 400 mg once daily for all indications. The tablets are swallowed whole with a glass of water. They can be taken independent of food intake.
Duration of Treatment: The duration of treatment should be determined by the severity of the indication or clinical response. The following general recommendations for the treatment of upper and lower respiratory tract infections are made: Acute Exacerbation of Chronic Bronchitis: 5 days.
Community-Acquired Pneumonia: 10 days for the tablet and 7-14 days for the infusion solution.
Acute Sinusitis: 7 days.
Uncomplicated Skin and Skin Structure Infections: 7 days.
Uncomplicated Pelvic Inflammatory Disease: 14 days.
Complicated Skin and Skin Structure Infections for Sequential Therapy (IV followed by Oral Therapy): 7-21 days.
Complicated Intra-Abdominal Infections for Sequential Therapy (IV followed by Oral Therapy): 5-14 days.
Infuse over a period of 60 min. The recommended duration of treatment for the indication being treated should not be exceeded. Avelox 400-mg tablets have been studied in clinical trials for up to 21 days (in complicated skin and skin structure infections).
Elderly: No dosage adjustment is required in the elderly.
Inter-Ethnic Differences: No dosage adjustment is required in ethnic groups.
Hepatic Impairment: No dosage adjustment is required in patients with impaired liver function (see Precautions).
Renal Impairment: No dose adjustment is required in patients with any degree of renal impairment (including creatinine clearance ≤30 mL/min/1.73 m2) and in patients on chronic dialysis ie, hemodialysis and continuous ambulatory peritoneal dialysis.
Overdosage
Only limited data on overdose are available. Single doses of up to 1200 mg and multiple doses of 600 mg over 10 days were administered to healthy subjects without any significant undesirable effects. In the event of overdosage, it is recommended that appropriate supportive care including electrocardiogram (ECG) measurements should be instituted as dictated by the patient's clinical status.
The use of charcoal early after oral administration may be useful to prevent excessive increase of systemic exposure to moxifloxacin in cases of overdosage.
Contraindications
Hypersensitivity to other quinolones, moxifloxacin or any of the excipients of Avelox.
Use in Pregnancy: The safe use of moxifloxacin in human pregnancy has not been established. 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.
Consequently, the use of moxifloxacin during pregnancy is contraindicated.
Use in Lactation: As with other quinolones, moxifloxacin has been shown to cause lesions in the cartilage of the weight bearing joints of immature animals. Preclinical evidence indicates that small amounts of moxifloxacin may be secreted in human milk. There is no data available in lactating or nursing women. Therefore, the use of moxifloxacin in nursing mothers is contraindicated.
Use in Children: Safety and efficacy of moxifloxacin in children and adolescents have not been established.
Special Precautions
In some instances, the hypersensitivity and allergic reactions already occurred after the 1st administration and the doctor should be informed immediately.
Anaphylactic reactions in very rare instances can progress to a life-threatening shock, in some instances after the 1st administration. In these cases moxifloxacin has to be discontinued, medical treatment (eg, treatment for shock) is required.
Moxifloxacin has been shown to prolong the QT interval of the ECG in some patients. It should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalaemia and patients receiving class IA (eg, quinidine, procainamide) or class III (eg, amiodarone, sotalol) antiarrhythmic agents, due to the lack of clinical experience with the drug in these patient populations.
An additive effect of moxifloxacin and drugs that prolong the QT interval eg, cisapride, erythromycin, antipsychotics and tricyclic antidepressants cannot be excluded. Therefore, moxifloxacin should be used with caution when given concurrently with these drugs.
Moxifloxacin should be used with caution in patients with ongoing pro-arrhythmic conditions eg, clinically significant bradycardia, acute myocardial ischemia.
As the magnitude of QT prolongation may increase with increasing concentrations of the drug, the recommended dose should not be exceeded. However, in patients suffering from pneumonia, no correlation between plasma concentrations of moxifloxacin and QTc prolongation was observed. QT prolongation may lead to an increased risk for ventricular arrhythmias including Torsade de pointes. No cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin treatment in clinical studies with >9000 patients, however certain predisposing conditions may increase the risk for ventricular arrhythmias.
Seizures may occur with quinolone therapy. Moxifloxacin should be used with caution in patients with known or suspected CNS disorders which may predispose to seizures or lower the seizure threshold.
Due to limited clinical data, the use of moxifloxacin is not recommended in patients with severe hepatic impairment (Child-Pugh C).
Antibiotic-associated colitis has been reported with the use of broad-spectrum antibiotics including moxifloxacin, therefore, it is important to consider this diagnosis in patients who develop serious diarrhoea in association with the use of moxifloxacin. In this clinical situation, adequate therapeutic measures should be initiated immediately.
Tendon inflammation and rupture may occur with quinolone therapy including moxifloxacin, particularly in elderly patients and in those treated concurrently with corticosteroids. At the 1st sign of pain or inflammation, patients should discontinue treatment and rest the affected limbs.
Quinolones have been shown to cause photosensitivity reactions 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 ultraviolet irradiation or sunlight.
For patients with complicated pelvic inflammatory disease (eg, associated with a tubo-ovarian or pelvic abscess), for whom an IV treatment is considered necessary, treatment with moxifloxacin 400 mg tablets is not recommended.
Effect on the Ability to Drive or Operate Machinery: In clinical trials, a low incidence of CNS reactions was observed. However, patients should be cautioned to see how they react before driving or operating machinery.
Use In Pregnancy & Lactation
Use in Pregnancy: The safe use of moxifloxacin in human pregnancy has not been established. 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.
Consequently, the use of moxifloxacin during pregnancy is contraindicated.
Use in Lactation: As with other quinolones, moxifloxacin has been shown to cause lesions in the cartilage of the weight bearing joints of immature animals. Preclinical evidence indicates that small amounts of moxifloxacin may be secreted in human milk. There is no data available in lactating or nursing women. Therefore, the use of moxifloxacin in nursing mothers is contraindicated.
Adverse Reactions
Adverse drug reactions (ADRs) based on all clinical studies with moxifloxacin 400 mg (oral and sequential therapy) sorted by CIOMS III categories of frequency (overall n=12,984, including n=2535 for sequential therapy studies; status: December 2005) are as follows. ADRs listed under "common" were observed with a frequency below 3% with the exception of nausea and diarrhoea.
ADRs derived from post-marketing reports (status: September 2006) are marked with (*).
Frequencies are defined by the following conventions: Common (≥1% to <10%); uncommon (≥0.1% to <1%); rare (≥0.01% to <0.1%); very rare (<0.01%).
Infections and Infestations: Antibiotic-Induced Superinfections: Common: Mycotic superinfections.
Blood and Lymphatic System Disorders: Changes In Blood Cell Counts: Uncommon: Anemia, leucopenia, neutropenia, thrombocytopenia, thrombocythemia. Changes in Coagulation: Uncommon: Prolonged prothrombin time/increased INR. Rare: Abnormal thromboplastin level. Very Rare: Increased prothrombin level/decreased INR, abnormal prothrombin level/INR.
Immune System Disorders: Acute Hypersensitivity Reactions: Uncommon: Allergic reaction, pruritus, rash, urticaria, blood eosinophilia. Rare: Anaphylactic/anaphylactoid reaction, allergic edema/angioedema (including potentially life-threatening laryngeal edema). Very Rare: Anaphylactic/anaphylactoid shock (potentially life-threatening).
Metabolism and Nutritional Disorders: Changes in Laboratory Parameters: Uncommon: Hyperlipidemia. Rare: Hyperglycemia, hyperuricemia.
Psychiatric Disorders: Behavioural Disturbances: Uncommon: Anxiety reactions, psychomotor hyperactivity/agitation. Rare: Emotional lability, depression (in very rare cases, potentially culminating in self-endangering behaviour*), hallucinations. Very Rare: Depersonalization, psychotic reactions (potentially culminating in self-endangering behaviour*).
Nervous System Disorders: Unspecific Altered Peripheral Perception: Uncommon: Paresthesia, dysesthesia. Rare: Hypoesthesia. Very Rare: Hyperesthesia.
Smell and Taste Disorders: Uncommon: Taste disorder (including ageusia in very rare cases). Rare: Smell disorders (including anosmia).
Increased Neurological Activities: Common: Headache, dizziness. Uncommon: Confusion and disorientation, sleep disorder, tremor, vertigo. Rare: Abnormal dreams, disturbed coordination (including gait disturbances especially due to dizziness or vertigo; in very rare cases leading to fall with injuries especially in the elderly*), seizures of various clinical manifestations (including grand mal convulsions).
Decreased Neurological Activities: Uncommon: Somnolence. Rare: Disturbed attention, speech disorders, amnesia.
Eye Disorders: Uncommon: Visual disturbances (especially in the course of CNS reactions).
Ear and Labyrinth Disorders: Rare: Tinnitus.
Cardiovascular System Disorders: Repolarisation Disorders: Common: QT prolongation in patients with hypokalemia. Uncommon: QT prolongation.
Unspecific Arrhythmias: Uncommon: Palpitations, tachycardia. Very Rare: Unspecified arrhythmias.
Ventricular Arrhythmias: Rare: Ventricular tachyarrhythmias. Very Rare: Torsade de pointes*; cardiac arrest especially in patients with severe underlying proarrhythmic conditions eg, clinically significant bradycardia, acute myocardial ischemia*.
Unspecified Cardiovascular Symptoms: Uncommon: Vasodilatation. Rare: Syncope, hypertension, hypotension.
Respiratory, Thoracic and Mediastinal Disorders: Uncommon: Dyspnea (including asthmatic conditions).
Gastrointestinal Disorders: Gastrointestinal Symptoms: Common: Nausea, vomiting, gastrointestinal and abdominal pains. Uncommon: Anorexia, constipation, dyspepsia, flatulence, gastroenteritis (excluding erosive gastroenteritis), increased amylase. Rare: Dysphagia, stomatitis.
Antibiotic-Induced Diarrheal Disorders: Common: Diarrhea. Rare: Pseudomembranous colitis (in very rare cases associated with life-threatening complications).
Hepatobiliary Disorders: Mild to Moderate Hepatic Reactions: Common: Increased transaminases. Uncommon: Hepatic impairment (including increased LDH), increased bilirubin, increased γ-glutamyl transferase, increased blood alkaline phosphatase.
Severe Hepatic Reactions: Rare: Jaundice, hepatitis (predominantly cholestatic). Very Rare: Fulminant hepatitis (potentially leading to life-threatening liver failure*.
Skin and Subcutaneous Tissue Disorders: Bullous Skin Reactions: Very Rare: Bullous skin reactions eg, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening)*.
Musculoskeletal and Connective Tissue Disorders: Tendon Disorders:
Rare: Tendonitis. Very Rare: Tendon rupture.
Unspecific Joint and Muscular Disorders: Uncommon: Arthralgia, myalgia. Rare: Increased muscle tone and cramping. Very Rare: Arthritis, gait disturbance (caused by muscular, tendon or joint symptoms)*.
Renal and Urinary Disorders: Renal Impairment: Uncommon: Dehydration (caused by diarrhea or reduced fluid intake). Rare: Renal impairment, renal failure (due to dehydration especially in elderly with preexisting renal disorders).
General Disorders and Administration Site Conditions: General Feeling of Illness: Uncommon: Feeling unwell, unspecific pain, sweating.
Infusion Site Reactions: Common: Injection and infusion site reactions. Uncommon: Infusion site thrombophlebitis.
General Disorders: Rare: Edema.
Drug Interactions
Tablet: 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 Multivitamins: Concomitant ingestion of moxifloxacin with antacids, minerals and multivitamins may result in impaired absorption of moxifloxacin after oral administration due to formation of chelate complexes with the multivalent cations contained in these preparations. This may lead to plasma concentrations considerably lower than desired. Hence, antacids, antiretroviral drugs (eg, didanosine) 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.
Ranitidine: The concomitant administration with ranitidine did not change the absorption characteristics of moxifloxacin. Absorption parameters (Cmax, tmax, AUC) were comparable, indicating absence of an influence of gastric pH on moxifloxacin uptake from the gastrointestinal tract.
Calcium Supplements: When given with high dose calcium supplements, only a slightly reduced rate of absorption was observed, while extent of absorption remained unaffected. The effect of high-dose calcium supplements on the absorption of moxifloxacin is considered as clinically not relevant.
Theophylline: In accordance with in vitro data, no influence of moxifloxacin on theophylline pharmacokinetics (and vice versa) at steady state was detected in humans, indicating that moxifloxacin does not interfere with the 1A2 subtypes of the CYP450 enzymes.
Warfarin: No interaction during concomitant treatment with warfarin on pharmacokinetics, prothrombin time and other coagulation parameters has been observed.
Changes in International Normalized Ratio (INR): 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.
Oral Contraceptives: No interaction has occured following concomitant oral administration of moxifloxacin with oral contraceptives.
Antidiabetics: No clinically relevant interaction was seen between glibenclamide and moxifloxacin.
Itraconazole: Exposure (AUC) to itraconazole was only marginally altered under concomitant moxifloxacin treatment. Pharmacokinetics of moxifloxacin were not significantly altered by itraconazole. No dose adjustment is necessary for itraconazole when given with moxifloxacin and vice versa.
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.
Morphine: Parenteral administration of morphine with moxifloxacin did not reduce the oral bioavailability of moxifloxacin and only slighlty decreased Cmax (17%).
Atenolol: The pharmacokinetics of atenolol are not significantly altered by moxifloxacin. Following single dose administration in healthy subjects, AUC was marginally increased (by approximately 4%) and peak concentrations were decreased by 10%.
Probenecid: No significant effect on apparent total body clearance and renal clearance of moxifloxacin was found in a clinical study investigating the impact of probenecid on renal excretion.
Charcoal: Concomitant dosing of charcoal and oral moxifloxacin 400 mg reduced the systemic availability of the drug by >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 IV drug administration, carbo medicinalis only slightly reduces systemic exposure (approximately 20%).
Food and Dairy Products: Absorption of moxifloxacin was not altered by food intake (including dairy products). Moxifloxacin can be taken independent from food intake.
Infusion: No interaction during concomitant treatment with warfarin, itraconazole, theophylline, digoxin and oral contraceptives.
Storage
Store in a dry place.
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 x 5's. Infusion bag 400 mg/250 mL (flexi bag) x 1's.
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