Mofacin

Mofacin

moxifloxacin

Manufacturer:

Nang Kuang Pharmaceutical

Distributor:

Symgens

Marketer:

Symgens
Full Prescribing Info
Contents
Moxifloxacin hydrochloride.
Description
Each mL contains Moxifloxacin hydrochloride 1.746 mg (eq. to Moxifloxacin 1.6mg (Potency)).
Excipients/Inactive Ingredients: Solution for infusion: hydrochloric acid 1N, sodium chloride, sodium hydroxide solution 2N, water for injection.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Moxifloxacin is an 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 e.g. Chlamydia spp., Mycoplasma spp. 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. Moxifloxacin is effective against β-lactam and macrolide resistant bacteria. Studies in animal models of infection have demonstrated 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. (See Tables 1, 2, 3 and 4.)

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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 above 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 hospitalization 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 5.

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Pharmacokinetics: Absorption: Moxifloxacin, given as an oral tablet, is well absorbed from the gastrointestinal tract. The absolute bioavailability of moxifloxacin is approximately 90 percent. Co-administration with a high fat meal (i.e., 500 calories from fat) does not affect the absorption of moxifloxacin.
Consumption of 1 cup of yogurt with moxifloxacin does not significantly affect the extent or rate of systemic absorption (AUC).
The mean (±SD) Cmax and AUC values following single and multiple doses of 400 mg moxifloxacin given orally are summarized as follows. (See Table 6.)

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The mean (±SD) Cmax and AUC values following single and multiple doses of 400 mgmoxifloxacin given by 1 hour I.V. infusion are summarized as follows. (See Table 7.)

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Plasma concentrations increase proportionately with dose up to the highest dose tested (1200 mg single oral dose). The mean (±SD) elimination half-life from plasma is 12±1.3 hours; steady-state is achieved after at least three days with a 400 mg once daily regimen. (See Figure.)

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Distribution: Moxifloxacin is approximately 30-50% bound to serum proteins, independent of drug concentration. The volume of distribution of moxifloxacin ranges from 1.7 to 2.7 L/kg. Moxifloxacin is widely distributed throughout the body, with tissue concentrations often exceeding plasma concentrations. Moxifloxacin has been detected in the saliva, nasal and bronchial secretions, mucosa of the sinuses, skin blister fluid, subcutaneous tissue, skeletal muscle and abdominal tissues and fluids following oral or intravenous administration of 400 mg.
Moxifloxacin concentrations measured post-dose in various tissues and fluids following a 400mg oral or I.V. dose are summarized in the following table. The rates of elimination of moxifloxacin from tissues generally parallel the elimination from plasma. (See Table 8.)

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Metabolism: Approximately 52% of an oral or intravenous dose of moxifloxacin is metabolized via glucuronide and sulfate conjugation. The cytochrome P450 system is not involved in moxifloxacin metabolism, and is not affected by moxifloxacin. The sulfate conjugate (M1) accounts for approximately 38% of the dose, and is eliminated primarily in the feces. Approximately 14% of an oral or intravenous dose is converted to a glucuronide conjugate (M2), which is excreted exclusively in the urine.
Peak plasma concentrations of M2 are approximately 40% those of the parent drug, while plasma concentrations of M1 are generally less than 10% those of moxifloxacin.
In vitro studies with cytochrome (CYP) P450 enzymes indicate that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2, suggesting that moxifloxacin is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes.
Excretion: Approximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces). A total of 96 ± 4% of an oral dose is excreted as either unchanged drug or known metabolites. The mean (±SD) apparent total body clearance and renal clearance are 12 ± 2.0 L/hr and 2.6 ± 0.5 L/hr, respectively.
Special Populations: Geriatric: Following oral administration of 400 mg moxifloxacin for 10 days in 16 elderly (8 males; 8 females) and 17 (8 males; 9 females) young healthy volunteers, there were no age-related changes in moxifloxacin pharmacokinetics. In 16 healthy male volunteers (8 young; 8 elderly males) given a single 200 mg dose of oral moxifloxacin, the extent of systemic exposure (AUC and Cmax) was not statistically different between young and elderly males and elimination half-life was unchanged. No dosage adjustment is necessary based on age. In large phase III studies, the concentrations around the time of the end of the infusion in elderly patients following intravenous infusion of 400 mg were similar to those observed in young patients.
Pediatric: The pharmacokinetics of moxifloxacin in pediatric subjects have not been studied.
Gender: Following oral administration of 400 mg moxifloxacin daily for 10 days to 23 healthy males (19-75 years) and 24 healthy females (19-70 years), the mean AUC and Cmax were 8% and 16% higher, respectively, in females compared to males. There are no significant differences in moxifloxacin pharmacokinetics between male and female subjects when differences in body weight are taken into consideration. A 400 mg single dose study was conducted in 18 young males and females. The comparison of moxifloxacin pharmacokinetics in this study (9 young females and 9 young males) showed no differences in AUC or Cmax due to gender. Dosage adjustments based on gender are not necessary.
Race: Steady-state moxifloxacin pharmacokinetics in male Japanese subjects were similar to those determined in Caucasians, with a mean Cmax of 4.1µg/mL, an AUC24 of 47µg·hr/mL, and an elimination half-life of 14 hours, following 400 mg oral daily.
Renal Insufficiency: The pharmacokinetic parameters of moxifloxacin are not significantly altered in mild, moderate, severe, or end-stage renal disease. No dosage adjustment is necessary in patients with renal impairment, including those patients requiring hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).
In a single oral dose study of 24 patients with varying degrees of renal function from normal to severely impaired, the mean peak concentrations (Cmax) of moxifloxacin were reduced by 21% and 28% in the patients with moderate (CLCR 30-60 mL/min) and severe (CLCR <30 mL/min) renal impairment, respectively. The mean systemic exposure (AUC) in these patients was increased by 13%. In the patients with moderate and severe renal impairment, the mean AUC for the sulfate conjugate (M1) increased by 1.7-fold (ranging up to 2.8-fold) and mean AUC and Cmax for the glucuronide conjugate (M2) increased by 2.8-fold (ranging up to 4.8-fold) and 1.4-fold (ranging up to 2.5-fold), respectively.
The pharmacokinetics of single-dose and multiple-dose moxifloxacin were studied in patients with CLCR < 20 mL/min on either hemodialysis or continuous ambulatory peritoneal dialysis (8 HD, 8 CAPD). Following a single 400 mg oral dose, the AUC of moxifloxacin in these HD and CAPD patients did not vary significantly from the AUC generally found in healthy volunteers. Cmax values of moxifloxacin were reduced by about 45% and 33% in HD and CAPD patients, respectively, compared to healthy, historical controls. The exposure (AUC) to the sulfate conjugate (M1) increased by 1.4- to 1.5-fold in these patients. The mean AUC of the glucuronide conjugate (M2) increased by a factor of 7.5, whereas the mean Cmax values of the glucuronide conjugate (M2) increased by a factor of 2.5 to 3, compared to healthy subjects. The sulfate and the glucuronide conjugates of moxifloxacin are not microbiologically active, and the clinical implication of increased exposure to these metabolites in patients with renal disease including those undergoing HD and CAPD has not been studied.
Oral administration of 400 mg daily moxifloxacin for 7 days to patients on HD or CAPD produced mean systemic exposure (AUCss) to moxifloxacin similar to that generally seen in healthy volunteers. Steady-state Cmax values were about 22% lower in HD patients but were comparable between CAPD patients and healthy volunteers. Both HD and CAPD removed only small amounts of moxifloxacin from the body (approximately 9% by HD, and 3% by CAPD). HD and CAPD also removed about 4% and 2% of the glucuronide metabolite (M2), respectively.
Hepatic Insufficiency: In 400 mg single oral dose studies in 6 patients with mild (Child Pugh Class A), and 10 patients with moderate (Child Pugh Class B), hepatic insufficiency, moxifloxacin mean systemic exposure (AUC) was 78% and 102%, respectively, of 18 healthy controls and mean peak concentration (Cmax) was 79% and 84% of controls.
The mean AUC of the sulfate conjugate of moxifloxacin (M1) increased by 3.9-fold (ranging up to 5.9-fold) and 5.7-fold (ranging up to 8.0-fold) in the mild and moderate groups, respectively. The mean Cmax of M1 increased by approximately 3-fold in both groups (ranging up to 4.7- and 3.9-fold). The mean AUC of the glucuronide conjugate of moxifloxacin (M2) increased by 1.5-fold (ranging up to 2.5-fold) in both groups. The mean Cmax of M2 increased by 1.6- and 1.3-fold (ranging up to 2.7- and 2.1-fold), respectively. The clinical significance of increased exposure to the sulfate and glucuronide conjugates has not been studied. No dosage adjustment is recommended for mild or moderate hepatic insufficiency (Child Pugh Classes A and B). The pharmacokinetics of moxifloxacin in severe hepatic insufficiency (Child Pugh Class C) have not been studied.
Photosensitivity Potential: A study of the skin response to ultraviolet (UVA and UVB) and visible radiation conducted in 32 healthy volunteers (8 per group) demonstrated that moxifloxacin does not show phototoxicity in comparison to placebo. The minimum erythematous dose (MED) was measured before and after treatment with moxifloxacin (200 mg or 400 mg once daily), lomefloxacin (400 mg once daily), or placebo. In this study, the MED measured for both doses of moxifloxacin were not significantly different from placebo, while lomefloxacin significantly lowered the MED.
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: Although conventional long-term studies to determine the carcinogenic potential of moxifloxacin have not been performed, the drug 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.
Phototoxicity: Moxifloxacin is very photostable and has a very low potential for photogenotoxicity. In vitro and in animal models, moxifloxacin seems to show less potency to induce phototoxicity and photogenotoxicity than other quinolones. Some quinolones have been shown to enhance the action of UV-A-induced photocarcinogenicity when administered concurrently to mice exposed to ultraviolet light. No photocarcinogenicity study has been performed with moxifloxacin. The lack of phototoxic potential has been confirmed in a Phase I study in volunteers.
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 diarthrodial 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 fetal 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
Mofacin 400 mg/250 mL infusion solution is indicated for the treatment of adults (≥18 years of age) with the following bacterial infections caused by susceptible strains: Respiratory tract infections (Acute sinusitis, Acute exacerbations of chronic bronchitis and Community acquired pneumonia); Skin and soft tissue infections; Complicated intra-abdominal infections including polymicrobial infections.
Dosage/Direction for Use
Dose regimen: Dosage in adult patients: The recommended dose for moxifloxacin is 400 mg once daily (250 mL solution for infusion) for the previously mentioned indications and should not be exceeded.
Duration: The duration of treatment should be determined by the type of the indication or clinical response. The following general recommendations for the treatment of upper and lower respiratory tract infections are: See Table 9.

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Method of administration: Mofacin infusion solution should be infused intravenously over 60 minutes.
The solution for infusion can be administered directly or via a T-tube together with compatible infusion solutions.
The following co-infusions were found to form stable mixtures over a period of 24 hours at room temperature with Moxifloxacin infusion solution, and can therefore be considered as compatible with Moxifloxacin infusion solution: Water for Injection; Sodium Chloride Injection 0.9%; Dextrose for Injection 5%; Dextrose for Injection 10%; Xylitol 20%; Ringer's Solution; Compound Sodium Lactate Solution (Hartmann's Solution, Lactated Ringer's Solution).
If Mofacin infusion solution is to be given with another drug, each drug should be given separately. (See Incompatibilities under Cautions for Usage). Only clear solutions are to be used.
Additional information on special populations: Geriatric Patients: No dosage adjustment is required in the elderly.
Children and adolescents: Efficacy and safety of Moxifloxacin in children and adolescents have not been established. (See Contraindications).
Ethnic differences: No dosage adjustment is required in ethnic groups.
Patients with hepatic impairment: No dosage adjustment is required in patients with hepatic impairment. (see Precautions).
Patients with renal impairment: No dosage adjustment is required in patients with any degree of renal impairment (including creatinine clearance ≤ 30mL/min/1.73m2) and in patients on chronic dialysis i.e. hemodialysis and continuous ambulatory peritoneal dialysis.
Overdosage
Only limited data on overdose are available. Single doses of up to 1,200 mg and multiple doses of 600 mg moxifloxacin 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 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 case of overdosage.
Contraindications
Known hypersensitivity to moxifloxacin or other quinolones or any of the excipients.
Pregnancy and lactation.
Patients below 18 years of age.
Special Precautions
Quinolones, including moxifloxacin have the risk of exacerbation of symptoms of myasthenia gravis, and patients with myasthenia gravis should avoid using the product.
In some instances, the hypersensitivity and allergic reactions already occurred after the first 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 first administration. In these cases the treatment with moxifloxacin has to be discontinued, medical treatment (e.g. treatment for shock) is required.
Moxifloxacin has been shown to prolong the QT interval of the electrocardiogram in some patients. As women tend to have a longer baseline QTc interval compared with men, they may be more sensitive to QTc-prolongation medications. Elderly patients may also be more susceptible to drug-associated effects on the QT interval.
As the magnitude of QT prolongation may increase with increasing concentrations of the drug, the recommended dose and the infusion rate (400 mg within 60 minutes) 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 torsades de pointes.
No cardiovascular morbidity or mortality attributable to QTc prolongation occurred with Moxifloxacin treatment in clinical studies with more than 9,000 patients; however certain predisposing conditions may increase the risk for ventricular arrhythmias.
Therefore, treatment with Moxifloxacin should be avoided due to the lack of clinical experience with the drug in these patient populations: in patients with known prolongation of the QTc interval; in patients with uncorrected hypokalemia; in patients receiving class IA (e.g. quinidine, procainamide) or class III (e.g. amiodarone, sotalol) antiarrhythmic agents.
Moxifloxacin should be used with caution as an additive effect of moxifloxacin on the QTc interval cannot be excluded for the following conditions: in patients treated concomitantly with drugs that prolong the QTc interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants; in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia, acute myocardial ischemia; in patients with liver cirrhosis as pre-existing QTc prolongation in these patients cannot be excluded; in women and elderly patients who, both, may be more susceptible to QTc-prolonging drugs.
Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with Moxifloxacin (see Adverse Reactions). Patients should be advised to contact their doctor immediately prior to continuing treatment if symptoms related to liver failure occur.
Cases of bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with Moxifloxacin (see Adverse Reactions). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.
Seizures may occur with quinolone therapy. It should be used with caution in patients with known or suspected CNS disorders which may predispose to seizures or lower the seizure threshold.
Antibiotics 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 diarrhea in association with the use of moxifloxacin. In this clinical situation adequate therapeutic measures should be initiated immediately. Drugs-induced inhibition of peristalsis are contraindicated in patients who develop serious diarrhea.
Moxifloxacin should be used with caution in patients with myasthenia gravis because the symptoms can be exacerbated.
Tendon inflammation and rupture may occur with quinolone therapy including moxifloxacin, particularly in elderly patients and in those treated concurrently with corticosteroids; cases occurring up to several months after completion of therapy have been reported. At the first sign of pain or inflammation, patients should discontinue treatment and rest the affected limb(s).
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 400 mg film-coated tablets is not recommended.
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 (see Pharmacology: Pharmacodynamics under Actions).
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.
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 (see Adverse Reactions).
Psychiatric reactions may occur even after the first administration of fluoroquinolones, including moxifloxacin. In very rare cases depression or psychotic reactions have progressed to suicidal thoughts and self-injurious behavior such as suicide attempts (see Adverse Reactions).
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 a history of psychiatric disease.
Because of the widespread and rising prevalence of fluoroquinolone resistant Neisseria gonorrhoeae infections, monotherapy with moxifloxacin should be avoided in patients with pelvic inflammatory disease, unless fluoroquinolone-resistant N. gonorrhoeae can be excluded.
If fluoroquinolone-resistant N. gonorrhoeae cannot be excluded, the addition of an appropriate antibiotic which is regularly active against N. gonorrhoeae (e.g., a cephalosporin) to empirical moxifloxacin therapy, should be considered.
Information about excipients: In patients for whom sodium intake is of medical concern (patients with congestive heart failure, renal failure, nephrotic syndrome, etc.) the additional sodium load of the solution for infusion should be taken into account. For sodium chloride content of the solution for infusion see Description.
Effects on Ability to Drive and Use Machines: Fluoroquinolones including moxifloxacin may result in an impairment of the patient's ability to drive or operate machinery due to CNS reactions (see Adverse Reactions).
Use In Pregnancy & Lactation
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 fetuses. Animal studies have shown reproductive toxicity. The potential risk for humans is unknown. Consequently, the use of moxifloxacin during pregnancy is contraindicated.
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 [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 below: ADRs listed under "common" were observed with a frequency below 3% with the exception of nausea and diarrhea.
ADRs derived from post marketing reports (status: May 2010) are printed in bold italic. 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 10.)

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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 (including grand mal convulsions), hallucination, renal impairment and renal failure (due to especially in elderly with pre-existing renal disorders).
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 dosage 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 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 (e.g. 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 GI-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 cytochrome P450 enzymes.
Warfarin: No interaction during concomitant treatment with warfarin on pharmacokinetics, prothrombin time and other coagulation parameters have 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.
Oral contraceptives: No interaction has occurred 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 was not significantly altered by itraconazole. No dosage adjustment is necessary for itraconazole when given with moxifloxacin and vice versa.
Digoxin: The pharmacokinetics of digoxin is 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 through levels.
Morphine: Parenteral administration of morphine with moxifloxacin did not reduce the oral bioavailability of moxifloxacin and only slightly decreased Cmax (17 %).
Atenolol: The pharmacokinetics of atenolol is 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 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 medicinal is only slightly reduces systemic exposure (by 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.
Caution For Usage
Instructions for use/handling: At cool storage temperatures precipitation may occur, which will redissolve at room temperature. It is therefore recommended not to store the infusion solution in a refrigerator.
Incompatibilities: The following co-infusions were found to be incompatible with moxifloxacin solution for infusion: Sodium Chloride 10%, Sodium Chloride 20%, Sodium Hydrogen Carbonate 4.2%, Sodium Hydrogen Carbonate 8.4%.
Storage
Store below 30°C; excursions permitted to 15-30°C; Do not keep in refrigerator.
MIMS Class
ATC Classification
J01MA14 - moxifloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
Presentation/Packing
Infusion soln 400 mg/250 mL x 1's.
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