MOXICIP Tablets (Moxifloxacin)

Table of Content

 

Black Box Warning

Serious Adverse Reactions Including Tendinitis, Tendon Rupture, Peripheral Neuropathy, Central Nervous System Effects And Exacerbation Of Myasthenia Gravis

Fluoroquinolones, including moxifloxacin have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including: 

  • Tendinitis and tendon rupture
  • Peripheral neuropathy
  • Central nervous system effects

Discontinue moxifloxacin immediately and avoid the use of fluoroquinolones, including moxifloxacin, in patients who experience any of these serious adverse reactions

  •  Fluoroquinolones, including moxifloxacin, may exacerbate muscle weakness in patients with myasthenia gravis. Avoid moxifloxacin in patients with known history of myasthenia gravis.
  • Because fluoroquinolones, including moxifloxacin, have been associated with serious adverse reactions, reserve moxifloxacin for use in patients who have no alternative treatment options for the following indications:
  1. Acute exacerbation of chronic bronchitis
  2. Acute bacterial sinusitis

This drug may cause low blood sugar and mental health related side effects

Composition

MOXICIP Tablets
Each film-coated tablet contains:
Moxifloxacin Hydrochloride
equivalent to Moxifloxacin ......................... 400 mg
Colours: Titanium Dioxide and Red Oxide of Iron

Dosage Form/S

400 mg oral tablet

Pharmacology

Pharmacodynamics

Mechanism of Action

Moxifloxacin is a member of the fluoroquinolone class of antibacterial agents

The bactericidal action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase I.V. required for bacterial DNA replication, transcription, repair, and recombination. It appears that the C8-methoxy moiety contributes to enhanced activity and lower selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety. The presence of the bulky bicycloamine substituent at the C-7 position prevents active efflux, associated with the NorA or pmrA genes seen in certain Gram-positive bacteria.

Mechanism of Resistance

The mechanism of action for quinolones, including moxifloxacin, is different from that of macrolides, beta-lactams, aminoglycosides or tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to moxifloxacin and other quinolones. Resistance to fluoroquinolones occurs primarily by a mutation in DNA gyrase or topoisomerase I.V. genes, decreased outer membrane permeability or drug efflux.

Cross-Resistance

Cross-resistance has been observed between moxifloxacin and other fluoroquinolones against Gram-negative bacteria. Gram-positive bacteria resistant to other fluoroquinolones may, however, still be susceptible to moxifloxacin. There is no known cross-resistance between moxifloxacin and other classes of antimicrobials.

Microbiology

Moxifloxacin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections:

Gram-positive Bacteria

Enterococcus faecalis

Staphylococcus aureus

Streptococcus anginosus

Streptococcus constellatus

Streptococcus pneumoniae (including multidrug-resistant strains )

Streptococcus pyogenes

Gram-negative Bacteria

Enterobacter cloacae

Escherichia coli

Haemophilus influenzae

Haemophilus parainfluenzae

Klebsiella pneumoniae

Moraxella catarrhalis

Proteus mirabilis

Anaerobic Bacteria

Bacteroides fragilis

Bacteroides thetaiotaomicron

Clostridium perfringens

Peptostreptococcus species

Other Microorganisms

Chlamydia pneumoniae

Mycoplasma pneumoniae

The following in vitro data are available, but their clinical significance is unknown.

At least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentrations (MIC) less than or equal to the susceptible breakpoint for moxifloxacin. However, the safety and efficacy of moxifloxacin in treating infections due to these bacteria has not been established in adequate and well controlled clinical trials.

Gram-positive Bacteria

Staphylococcus epidermidis

Streptococcus agalactiae

Streptococcus viridans group

Gram-negative Bacteria

Citrobacter freundii

Klebsiella oxytoca

Legionella pneumophila

Anaerobic Bacteria

Fusobacterium species

Prevotella species

Note

MDRSP: Multidrug-resistant Streptococcus pneumoniae includes isolates previously known as PRSP (penicillin-resistant S. pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin (MIC ≥2 µg/mL), second-generation cephalosporins (e.g. cefuroxime), macrolides, tetracyclines, and trimethoprim/sulphamethoxazole.

Pharmacokinetics

Absorption

Moxifloxacin, given as an oral tablet, is well absorbed from the gastrointestinal tract. The absolute bioavailability of moxifloxacin is approximately 90%. Co-administration with a high-fat meal (i.e. 500 calories from fat) does not affect the absorption of moxifloxacin. Consumption of one cup of yoghurt with moxifloxacin does not significantly affect the extent or rate of systemic absorption (AUC). The Cmax values after administration of a single, oral dose and I.V dose were found to be 3.1mg/L and 3.9mg/L, respectively, in healthy volunteers.

Plasma concentrations increase proportionately with dose up to the highest dose tested (1,200 mg single, oral dose).

Distribution

Moxifloxacin is approximately 30 to 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 (I.V.) administration of 400 mg. The rates of elimination of moxifloxacin from tissues generally parallel the elimination from plasma.

Metabolism

Approximately 52% of an oral or I.V. dose of moxifloxacin is metabolized via glucuronide and sulphate conjugation. The cytochrome (CYP) 450 system is not involved in moxifloxacin metabolism, and is not affected by moxifloxacin. The sulphate conjugate (M1) accounts for approximately 38% of the dose,and is eliminated primarily in the faeces. Approximately 14% of an oral or I.V. 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 CYP450 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

The mean elimination half-life from plasma is 12 hours; steady state is achieved after at least 3 days with a 400 mg once-daily regimen.

Approximately 45% of an oral or I.V. dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in faeces).

A total of 96% ± 4% of an oral dose is excreted as either unchanged drug or known metabolites. The mean apparent total body clearance and renal clearance are 12 ± 2 L/hr and 2.6 ± 0.5 L/hr, respectively.

Pharmacokinetics in Specific Populations

Geriatric

Following oral administration of 400 mg moxifloxacin for 10 days in 16 elderly (8 male; 8 female) and 17 young (8 male; 9 female) healthy volunteers, there were no age-related changes in moxifloxacin pharmacokinetics. In 16 healthy male volunteers (8 young; 8 elderly) 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 the 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 I.V. infusion of 400 mg were similar  to those observed in young patients.

Paediatric

The pharmacokinetics of moxifloxacin in paediatric subjects has not been studied

Gender

Following oral administration of 400 mg moxifloxacin daily for 10 days to 23 healthy males (aged 19 to 75 years) and 24 healthy females (aged 19 to 70 years), the mean AUC and Cmax were 8% and 16% higher, respectively, in females compared with 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 the 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 4.1 mcg/mL, an AUC24 of 47 mcg•h/mL, and an elimination half-life of 14 hours, following 400 mg PO daily.

Renal Impairment

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 haemodialysis 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 and ≤ 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 moderate and severe renally impaired patients, the mean AUC for the sulphate 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 haemodialysis or CAPD (8 haemodialysis, 8 CAPD). Following a single 400 mg oral dose, the AUC of moxifloxacin in these haemodialysis and CAPD patients did not vary significantly from the AUC generally found in healthy volunteers. The Cmax values of moxifloxacin were reduced by about 45% and 33% in haemodialysis and CAPD patients, respectively, compared with healthy, historical controls. The exposure (AUC) to the sulphate 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 with healthy subjects. The sulphate 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 haemodialysis and CAPD has not been studied.

Oral administration of 400 mg q.d. moxifloxacin for 7 days to patients on haemodialysis 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 Impairment

No dosage adjustment is recommended for mild, moderate or severe hepatic impairment (Child-Pugh Classes A, B or C). However, due to metabolic disturbances associated with hepatic impairment, which may lead to QT prolongation, moxifloxacin should be used with caution in these patients.

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 impairment, 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 sulphate conjugate of moxifloxacin (M1) increased by 3.9-fold (ranging up to 5.9-fold) and 5.7-fold (ranging up to 8-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 sulphate and glucuronide conjugates has not been studied. In a subset of patients participating in a clinical trial, the plasma concentrations of moxifloxacin and metabolites determined approximately at the moxifloxacin Tmax following the first I.V. or oral moxifloxacin dose in the Child-Pugh Class C patients (n=10) were similar to those in the Child-Pugh Class A/B patients (n=5), and also similar to those observed in healthy volunteer studies.

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 with 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.

It is difficult to ascribe relative photosensitivity/phototoxicity among various fluoroquinolones during actual patient use because other factors play a role in determining a subject’s susceptibility to this adverse event such as the following: a patient’s skin pigmentation, frequency and duration of sun and artificial ultraviolet light (UV) exposure, wearing of sunscreen and protective clothing, the use of other concomitant drugs and the dosage and duration of fluoroquinolone therapy.

Drug–Drug Interactions

The following drug interactions were studied in healthy volunteers or patients.

Antacids and iron significantly reduced the bioavailability of moxifloxacin, as observed with other quinolones.

Calcium, digoxin, itraconazole, morphine, probenecid, ranitidine, theophylline and warfarin did not significantly affect the pharmacokinetics of moxifloxacin. These results and the data from in vitro studies suggest that moxifloxacin is unlikely to significantly alter the metabolic clearance of drugs metabolized by CYP3A4, CYP2D6, CYP2C9, CYP2C19 or CYP1A2 enzymes.

Moxifloxacin had no clinically significant effect on the pharmacokinetics of atenolol, digoxin, glyburide, itraconazole, oral contraceptives, theophylline and warfarin.

Antacids

When moxifloxacin (single 400 mg tablet dose) was administered 2 hours before, concomitantly, or 4 hours after an aluminium-/magnesium-containing antacid (900 mg aluminium hydroxide and 600 mg magnesium hydroxide as a single oral dose) to 12 healthy volunteers, there was a 26%, 60% and 23% reduction in the mean AUC of moxifloxacin, respectively. Moxifloxacin should be taken at least 4 hours before or 8 hours after antacids containing magnesium or aluminium, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc, didanosine chewable/ buffered tablets or the paediatric powder for oral solution.

Atenolol

In a crossover study involving 24 healthy volunteers (12 male; 12 female), the mean atenolol AUC following a single oral dose of 50 mg atenolol with placebo was similar to that observed when atenolol was given concomitantly with a single 400 mg oral dose of moxifloxacin. The mean Cmax of single-dose atenolol decreased by about 10% following co-administration with a single dose of moxifloxacin.

Calcium

In 12 healthy volunteers, concomitant moxifloxacin (single 400 mg dose) and calcium (single dose of 500 mg Ca++ dietary supplement) were administered, followed by an additional two doses of calcium at 12 and 24 hours after moxifloxacin administration. Calcium had no significant effect on the mean AUC of moxifloxacin. The mean Cmaxwas slightly reduced and the time to maximum plasma concentration was prolonged when moxifloxacin was given with calcium compared to when moxifloxacin was given alone (2.5 hours versus 0.9 hours). These differences are not considered to be clinically significant.

Digoxin

No significant effect of moxifloxacin (400 mg once daily for 2 days) on digoxin (0.6 mg as a single dose) AUC was detected in a study involving 12 healthy volunteers. The mean digoxin Cmax increased by about 50% during the distribution phase of digoxin. This transient increase in digoxin Cmax is not viewed to be clinically significant. Moxifloxacin pharmacokinetics was similar in the presence or absence of digoxin. No dosage adjustment for moxifloxacin or digoxin is required when these drugs are administered concomitantly.

Glyburide

In diabetics, glyburide (2.5 mg once daily for 2 weeks pre-treatment and for 5 days concurrently) mean AUC and Cmaxwere 12% and 21% lower, respectively, when taken with moxifloxacin (400 mg once daily for 5 days) in comparison with placebo. Nonetheless, blood glucose levels were decreased slightly in patients taking glyburide and moxifloxacin in comparison with those taking glyburide alone, suggesting no interference by moxifloxacin on the activity of glyburide. These interaction results are not viewed as clinically significant.

Iron

When moxifloxacin tablets were administered concomitantly with iron (ferrous sulphate 100 mg once daily for 2 days), the mean AUC and Cmax of moxifloxacin was reduced by 39% and 59%, respectively. Moxifloxacin should only be taken more than 4 hours before or 8 hours after iron products.

Itraconazole

In a study involving 11 healthy volunteers, there was no significant effect of itraconazole (200 mg once daily for 9 days), a potent inhibitor of CYP450 3A4, on the pharmacokinetics of moxifloxacin (a single 400 mg dose given on the day 7 of itraconazole dosing). In addition, moxifloxacin was shown not to affect the pharmacokinetics of itraconazole.

Morphine

No significant effect of morphine sulphate (a single 10 mg intramuscular dose) on the mean AUC and Cmax of moxifloxacin (400 mg single dose) was observed in a study of 20 healthy male and female volunteers.

Oral Contraceptives

A placebo-controlled study in 29 healthy female subjects showed that moxifloxacin 400 mg daily for 7 days did not interfere with the hormonal suppression of oral contraception with 0.15 mg levonorgestrel/0.03 mg ethinyloestradiol (as measured by serum progesterone, FSH, oestradiol, and LH), or with the pharmacokinetics of the administered contraceptive agents.

Probenecid

Probenecid (500 mg twice daily for 2 days) did not alter the renal clearance and total amount of moxifloxacin (400 mg single dose) excreted renally in a study of 12 healthy volunteers.

Ranitidine

No significant effect of ranitidine (150 mg twice daily for 3 days as pre-treatment) on the pharmacokinetics of moxifloxacin (400 mg single dose) was detected in a study involving 10 healthy volunteers.

Theophylline

No significant effect of moxifloxacin (200 mg every 12 hours for 3 days) on the pharmacokinetics of theophylline (400 mg every 12 hours for 3 days) was detected in a study involving 12 healthy volunteers. In addition, theophylline was not shown to affect the pharmacokinetics of moxifloxacin. The effect of co-administration of a 400 mg dose of moxifloxacin with theophylline has not been studied, but it is not expected to be clinically significant based on in vitro metabolic data showing that moxifloxacin does not inhibit the CYP1A2 isoenzyme.

Warfarin

No significant effect of moxifloxacin (400 mg once daily for 8 days) on the pharmacokinetics of R- and S-warfarin (25 mg single dose of warfarin sodium on day 5) was detected in a study involving 24 healthy volunteers. No significant change in the prothrombin time was observed.

Indications

MOXICIP Tablets are indicated for the treatment of adults (≥18 years of age) with infections caused by susceptible isolates of the designated microorganisms in the conditions listed below:

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, methicillin-susceptible Staphylococcus aureus or Moraxella catarrhalis.

Note: Because fluoroquinolones, including moxifloxacin, have been associated with serious adverse reactions and for some patients ABECB is self-limiting, reserve moxifloxacin for treatment of ABECB in patients who have no alternative treatment options.

Community-acquired Pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains*), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae.

Note: * MDRSP, i.e. multidrug-resistant Streptococcus pneumoniae includes isolates previously known as PRSP (penicillin-resistant S. pneumoniae),and are strains resistant to two or more of the following antibiotics: penicillin (MIC ≥2 µg/mL), second-generation cephalosporins (e.g. cefuroxime), macrolides, tetracyclines, and trimethoprim/sulphamethoxazole.

Note:

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to moxifloxacin. Therapy with MOXICIP tablets may be initiated before the results of these tests are known; once the results become available, appropriate therapy should be continued.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of MOXICIP tablets and other antibacterial drugs, MOXICIP tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Dosage and Administration

The dose of MOXICIP tablets is 400 mg (orally or as an I.V. infusion) once every 24 hours. The duration of therapy depends on the type of infection as described below in Table 1.

Table 1

Infectiona

Dose
Every 24 hours

Durationb

 

Acute Bacterial Sinusitis

400 mg

10 days

Acute Bacterial Exacerbation of Chronic Bronchitis

400 mg

5 days

Community-acquired
Pneumonia

400 mg

7 to 14 days

Note:

a Due to the designated pathogens

bSequential therapy (intravenous to oral) may be instituted at the discretion of the physician

Conversion of Intravenous to Oral Dosing in Adults

The I.V. formulation is indicated when it offers a route of administration advantageous to the patient (e.g. patient cannot tolerate an oral dosage form). When switching from I.V. to oral formulation, 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.

Renal Impairment

The pharmacokinetic parameters of moxifloxacin are not significantly altered in mild, moderate, severe or end-stage renal disease No dosage adjustment is required in renally impaired patients, including those on either haemodialysis or CAPD.

Hepatic Impairment

No dosage adjustment is recommended for mild, moderate or severe hepatic impairment (Child-Pugh Classes A, B or C). However, due to metabolic disturbances associated with hepatic impairment, which may lead to QT prolongation, moxifloxacin should be used with caution in these patients.

Note

1)    Oral doses of moxifloxacin should be administered at least 4 hours before or 8 hours after products containing magnesium, aluminium, iron or zinc, including antacids, sucralfate, multivitamins and didanosine chewable/buffered tablets or the paediatric powder for oral solution.

2)    MOXICIP tablets can be taken with or without food, but drink fluids liberally.

Contraindications

Moxifloxacin is contraindicated in persons with a history of hypersensitivity to moxifloxacin or any member of the quinolone class of antimicrobial agents.

Warnings and Precautions

Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects

Fluoroquinolones, including moxifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting moxifloxacin. Patients of any age or without pre-existing risk factors have experienced these adverse reactions.

Discontinue moxifloxacin immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including moxifloxacin, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.

Tendinopathy and Tendon Rupture

Fluoroquinolones, including moxifloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported.

Tendinitis or tendon rupture can occur within hours or days of starting moxifloxacin or as long as several months after completion of therapy. Tendinitis and tendon rupture can occur bilaterally.

The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Moxifloxacin should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug.

Avoid fluoroquinolones, including moxifloxacin, in patients who have a history of tendon disorders or who have experienced tendinitis or tendon rupture

Peripheral Neuropathy

Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of 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 in some patients.

Discontinue moxifloxacin 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. Avoid fluoroquinolones, including moxifloxacin, in patients who have previously experienced peripheral neuropathy

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including moxifloxacin, have neuromuscular-blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing 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 known history of myasthenia gravis

QT Prolongation

Moxifloxacin has been shown to prolong the QT interval of the electrocardiogram in some patients. Following oral dosing with 400 mg of moxifloxacin the mean (± SD) change in QTc from the pre-dose value at the time of maximum drug concentration was 6 msec (± 26) (n = 787). Following a course of daily intravenous dosing (400 mg; 1 hour infusion each day) the mean change in QTc from the Day 1 pre-dose value was 10 msec (±22) on Day 1 (n=667) and 7 msec (± 24) on Day 3 (n = 667).

Avoid moxifloxacin in patients with the following risk factors due to the lack of clinical experience with the drug in these patient populations:

  • Known prolongation of the QT interval
  • Ventricular arrhythmias including torsade de pointes because QT prolongation may lead to an increased risk for these conditions
  • Ongoing proarrhythmic conditions, such as clinically significant bradycardia and acute myocardial ischemia,
  • Uncorrected hypokalemia or hypomagnesemia
  • Class IA (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic agents
  • Other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants

Elderly patients using intravenous moxifloxacin may be more susceptible to drug-associated QT prolongation.

In patients with mild, moderate, or severe liver cirrhosis, metabolic disturbances associated with hepatic insufficiency may lead to QT prolongation. Monitor ECG in patients with liver cirrhosis treated with moxifloxacin.

The magnitude of QT prolongation may increase with increasing concentrations of the drug or increasing rates of infusion of the intravenous formulation. Therefore the recommended dose or infusion rate should not be exceeded.

In premarketing clinical trials, the rate of cardiovascular adverse reactions was similar in 798 moxifloxacin and 702 comparator treated patients who received concomitant therapy with drugs known to prolong the QTc interval. No excess in cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin treatment in over 15,500 patients in controlled clinical studies, including 759 patients who were hypokalemic at the start of treatment, and there was no increase in mortality in over 18,000 moxifloxacin tablet treated patients in a postmarketing observational study in which ECGs were not performed.

Arthropathic Effects on Animals

The oral administration of moxifloxacin caused lameness in immature dogs. Histopathological examination of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage. Related quinolone-class drugs also produce erosions of cartilage of the weight-bearing joints and other signs of arthropathy in immature animals of various species.

Central Nervous System Effects

Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of central nervous system (CNS) reactions, including: convulsions and increased intracranial pressure (including pseudotumor cerebri) and toxic psychosis, Fluoroquinolones may also cause CNS reactions of nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and, suicidal thoughts or acts. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin, discontinue moxifloxacin immediately and institute appropriate measures. As with all fluoroquinolones, use moxifloxacin when the benefits of treatment exceed the risks in patients with known or suspected CNS disorders (for example, severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold.

Hypersensitivity Reactions

Serious anaphylactic reactions, some following the first dose, have been reported in patients receiving fluoroquinolone therapy, including moxifloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Discontinue moxifloxacin at the first appearance of a skin rash or any other sign of hypersensitivity

Other Serious, and Sometimes Fatal, Reactions

Other serious, and sometimes fatal, events, some due to hypersensitivity, and some due to uncertain aetiology, have been reported rarely in patients receiving therapy with quinolones, including moxifloxacin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

  • Fever, rash, or severe dermatologic reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome).
  • Vasculitis; arthralgia; myalgia; serum sickness.
  • Allergic pneumonitis.
  • Interstitial nephritis; acute renal impairment or failure.
  • Hepatitis; jaundice; acute hepatic necrosis or failure.
  • Anaemia, including haemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leucopenia; agranulocytosis; pancytopenia; and/or other haematologic abnormalities.

The drug should be discontinued immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted.

Clostridium difficile-Associated Diarrhoea

Clostridium difficile-associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents, including moxifloxacin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Blood Glucose Disturbances

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 (for example, sulfonylurea) or with insulin. In diabetic patients, careful monitoring of blood glucose is recommended. If a hypoglycemic reaction occurs, moxifloxacin should be discontinued and appropriate therapy should be initiated immediately

Photosensitivity / Phototoxicity

Moderate to severe photosensitivity / phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g. burning, erythema, exudation, vesicles, blistering, oedema) involving areas exposed to light (typically the face, ‘V’ area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of quinolone antibiotics after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs.

Development of Drug-Resistant Bacteria

Prescribing moxifloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Drug Interactions

Antacids, Sucralfate, Multivitamins and Other Products Containing Multivalent Cations

Quinolones form chelates with alkaline earth and transition metal cations. Oral administration of quinolones with antacids containing aluminium or magnesium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as didanosine chewable/buffered tablets or the paediatric powder for oral solution, may substantially interfere with the absorption of quinolones, resulting in systemic concentrations considerably lower than desired. Therefore, moxifloxacin should be taken at least 4 hours before or 8 hours after these agents.

Warfarin

Quinolones, including moxifloxacin, have been reported to enhance the anticoagulant effects of warfarin or its derivatives in the patient population. In addition, infectious disease and its accompanying inflammatory process, age and general status of the patient are risk factors for increased anticoagulant activity. Therefore the prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if a quinolone is administered concomitantly with warfarin or its derivatives.

Antidiabetic Agents

Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones, including moxifloxacin, and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered. If a hypoglycemic reaction occurs, moxifloxacin should be discontinued and appropriate therapy should be initiated immediately 

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Although not observed with moxifloxacin in preclinical and clinical trials, the concomitant administration of a NSAID with a quinolone may increase the risks of CNS stimulation and convulsions.

Drugs that Prolong QT

There is limited information available on the potential for a pharmacodynamic interaction in humans between moxifloxacin and other drugs that prolong the QTc interval of the ECG. Sotalol, a Class III anti-arrhythmic, has been shown to further increase the QTc interval when combined with high doses of I.V. moxifloxacin in dogs. Therefore, moxifloxacin should be avoided with class IA and class III anti-arrhythmics.

Renal Impairment

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).

Hepatic Impairment

No dosage adjustment is recommended for mild, moderate, or severe hepatic insufficiency (Child-Pugh Classes A, B, or C). However, due to metabolic disturbances associated with hepatic insufficiency, which may lead to QT prolongation, moxifloxacin should be used with caution in these patients

Pregnancy

Risk Summary

There are no available human data establishing a drug associated risk with the use of moxifloxacin.

Based on animal studies with moxifloxacin, Moxifloxacin may cause fetal harm. Moxifloxacin was not teratogenic when administered to pregnant rats (IV and oral), rabbits (IV), and monkeys (oral) at exposures that were 0.25–2.5 times of those at the human clinical dose (400 mg/day Moxifloxacin). However, when moxifloxacin was administered to rats and rabbits during pregnancy and throughout lactation (rats only) at doses associated with maternal toxicity, decreased neonatal body weights, increased incidence of skeletal variations (rib and vertebra combined), and increased fetal loss were observed (see Data). Advise pregnant women of the potential risk to the fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies.

Data

Animal Data

Animal reproductive and development studies were done in rats, rabbits and cynomolgus macaques. Moxifloxacin was not teratogenic when administered to pregnant rats during organogenesis (gestation days 6 to 17) at oral doses as high as 500 mg/kg/day or 0.24 times the maximum recommended human dose based on systemic exposure (AUC), but decreased fetal body weights and slightly delayed fetal skeletal development were observed. Intravenous administration of 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) to pregnant rats resulted in maternal toxicity and a marginal effect on fetal and placental weights and the appearance of the placenta (Gestation days 6 to 17). There was no evidence of teratogenicity at intravenous doses as high as 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) in pregnant rats during organogenesis (Gestation days 6 to 17). Intravenous administration of 20 mg/kg/day (approximately equal to the maximum recommended human oral dose based upon systemic exposure) to pregnant rabbits during organogenesis (gestation days 6 to 20) resulted in decreased fetal body weights and delayed fetal skeletal ossification. When rib and vertebral malformations were combined, there was an increased fetal and litter incidence of these effects in rabbits. Signs of maternal toxicity in rabbits at this dose included mortality, abortions, marked reduction of food consumption, decreased water intake, body weight loss and hypoactivity. There was no evidence of teratogenicity when pregnant cynomolgus macaques were given oral doses as high as 100 mg/kg/day (2.5 times the maximum recommended human dose based upon systemic exposure) during organogenesis (gestation days 20 to 50). An increased incidence of smaller fetuses was observed at 100 mg/kg/day in macaques. In a pre- and postnatal development study conducted in rats given oral doses from Gestation day 6, throughout gestation and rearing to Postpartum day 21, effects observed at 500 mg/kg/day (0.24 times the maximum recommended human dose based on systemic exposure (AUC)) included slight increases in duration of pregnancy and prenatal loss, reduced pup birth weight and decreased neonatal survival. Treatment-related maternal mortality occurred during gestation at 500 mg/kg/day in this study.

Lactation

Risk Summary

It is not known if moxifloxacin is present in human milk. Based on animal studies in rats, moxifloxacin may be excreted in human milk (see Data).

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for moxifloxacin and any potential adverse effects on the breastfed child from moxifloxacin or from the underlying maternal condition.

Data

In lactating rats given a single oral dose of 4.59 mg/kg moxifloxacin (approximately 9 times less than the recommended human dose based on body surface area) 8 days postpartum, there was very low excretion of substance-related radioactivity into the milk, amounting to approximately 0.03% of the dose.

Paediatric Use

Effectiveness in pediatric patients and adolescents less than 18 years of age has not been established. Moxifloxacin causes arthropathy in juvenile animals. Limited information on the safety of moxifloxacin in 301 pediatric patients is available from the cIAI trial.

Active Controlled Trial in Complicated Intra-Abdominal Infection (cIAI)

The safety and efficacy of moxifloxacin in pediatric patients for the treatment of cIAI has not been demonstrated.

Pediatric patients 3 months to <18 years of age (mean age of 12 ± 4 years) were enrolled in a single randomized, double-blind, active controlled trial in cIAI including appendicitis with perforation, abscesses and peritonitis.

Pediatric patients were randomized (2:1) to receive either moxifloxacin or comparator. This study enrolled 451 patients who received study medication, 301 treated with moxifloxacin, and 150 with comparator. Of the 301 pediatric patients treated with moxifloxacin, 15 were below the age of 6 years and 286 were between the ages of 6–<18 years.

Patients received sequential intravenous/oral moxifloxacin or comparator (intravenous ertapenem followed by oral amoxicillin/clavulanate) for 5 to 14 days (mean duration was 9 days with a range of 1 to 24 days).

The overall adverse reaction profile in pediatric patients was comparable to that of adult patients. The most frequently occurring adverse reactions in pediatric patients treated with moxifloxacin were QT prolongation 9.3% (28/301), vomiting, 6.6% (20/301) diarrhea 3.7% (11/301), arthralgia 3.0% (9/301), and phlebitis 2.7% (8/301) (see Table 5). Discontinuation of study drug due to an adverse reaction was reported in 5.3% (16/301) of moxifloxacin-treated patients versus 1.3% (2/150) of comparator-treated patients. The adverse reaction profile of moxifloxacin or comparator was similar across all age groups studied.

Musculoskeletal adverse reactions were monitored and followed up to 5 years after the end of study treatment. The rates of musculoskeletal adverse reactions were 4.3% (13/301) in the moxifloxacin-treated group versus 3.3% (5/150) in the comparator-treated group. The majority of musculoskeletal adverse reactions were reported between 12 and 53 weeks after start of study treatment with complete resolution at the end of the study.

Table 3: Table 3 incidence (%) of selected adverse reactions in ≥2.0% of pediatric patients treated with moxifloxacin in cIAI clinical trial

System Organ Class

Adverse Reactions

moxifloxacin 
N = 301 (%)

Comparator 
N = 150 (%)

Gastrointestinal disorders

Abdominal pain

8 (2.7)

3 (2.0)

 

Diarrhea

11 (3.7)

1 (0.7)

 

Vomiting

20 (6.6)

12 (8.0)

General disorders and administration site conditions

Pyrexia

6 (2.0)

4 (2.7)

Investigations

Aspartate aminotransferase increased

2 (0.7)

3 (2.0)

 

Electrocardiogram QT prolonged

28 (9.3)

4 (2.7)

Musculoskeletal and connective tissue disorders

Arthralgia

9 (3.0)

2 (1.3)

Nervous system disorders

Headache

6 (2.0)

2 (1.3)

Vascular disorders

Phlebitis

8 (2.7)

0 (0)

 

Clinical response was assessed at the test-of-cure visit (28 to 42 days after end of treatment). The clinical response rates observed in the modified intent to treat population were 83.9% (208/248) for moxifloxacin and 95.5% (127/133) for comparator; see Table 4.

Table 4: Clinical response rates at 28–42 days after end of treatment in pediatric patients with cIAI
 

Moxifloxacin

n (%)

Comparator

n (%)

Difference2

(95% CI)

mITT Population1

N=248

N=133

 

Cure

208 (83.9)

127 (95.5)

-12.2 (-17.9, -6.4)

Failure

17 (6.9)

3 (2.3)

 

Indeterminate

21 (8.5)

3 (2.3)

 

Missing

2 (0.8)

0

 

1The modified intent-to-treat (mITT) population is defined as all subjects who were treated with at least one dose of study medication and who have at least one pre-treatment causative organism from the intra-abdominal site of infection or from blood cultures.

2Difference in clinical cure rates (Moxifloxacin - Comparator) and 95% confidence intervals, presented as percentages, are based on stratified analysis by age group using Mantel-Haenszel methods.

 

Geriatric Use

Geriatric patients are at increased risk for developing severe tendon disorders, including tendon rupture when being treated with a fluoroquinolone such as moxifloxacin. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles tendon, hand, shoulder or other tendon sites, and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. Caution should be used when prescribing moxifloxacin to elderly patients, especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue moxifloxacin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur.

In controlled multiple-dose clinical trials, 23% of patients receiving oral moxifloxacin were ≥65 years of age and 9% were ≥75 years of age. The clinical trial data demonstrate that there is no difference in the safety and efficacy of oral moxifloxacin in patients aged 65 years or older, compared with younger adults.

In trials of I.V. use, 42% of moxifloxacin patients were ≥65 years of age, and 23% were ≥75 years of age. The clinical trial data demonstrate that the safety of I.V. moxifloxacin in patients aged 65 years or older was similar to that of comparator-treated patients. In general, elderly patients may be more susceptible to the drug-associated effects of the QT interval. Therefore, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval (e.g. class IA or class III anti-arrhythmics), or in patients with risk factors for torsades de pointes (e.g. known QT prolongation, uncorrected hypokalaemia).

Undesirable Effects

The data described below reflect exposure to moxifloxacin in 14981 patients in 71 active-controlled Phase II–IV clinical trials in different indications. The population studied had a mean age of 50 years (approximately 73% of the population was <65 years of age), 50% were male, 63% were Caucasian, 12% were Asian, and 9% were Black. Patients received moxifloxacin 400 mg once daily PO, I.V., or sequentially (I.V. followed by PO). Treatment duration was usually 6 to 10 days, and the mean number of days on therapy was 9 days.

Discontinuation of moxifloxacin due to adverse events occurred in 5.0% of patients overall, 4.1% of patients treated with 400 mg PO, 3.9% with 400 mg I.V., and 8.2% with sequential therapy 400 mg I.V./PO. The most common adverse events leading to discontinuation with 400 mg PO doses were nausea (0.8%), diarrhoea (0.5%), dizziness (0.5%), and vomiting (0.4%). The most common adverse events leading to discontinuation with the 400 mg I.V. dose was rash (0.5%). The most common adverse events leading to discontinuation with the 400 mg I.V./PO sequential dose were diarrhoea (0.5%), and pyrexia (0.4%). Adverse reactions occurring in ≥1% of moxifloxacin-treated patients and less common adverse reactions, occurring in 0.1 to <1% of moxifloxacin-treated patients, are shown in Table 4 and Table 5, respectively. The most common adverse drug reactions (≥3%) were nausea, diarrhoea, headache and dizziness.

Table 5: Common (≥1.0%) adverse reactions reported in active-controlled clinical trials with moxifloxacin.
 

System Organ Class

Adverse Reactions*

%

(N=14,981)

Blood and Lymphatic System Disorders

Anemia

1

Gastrointestinal Disorders

Nausea

7

 

Diarrhoea

6

 

Vomiting

2

 

Constipation

2

 

Abdominal pain

2

 

Dyspepsia

2

General Disorders and Administration Site Conditions

Pyrexia

1

Investigations

Alanine aminotransferase increased

1

Metabolism and Nutritional Disorder

Hypokalaemia

1

Nervous System Disorders

Headache

4

 

Dizziness

3

Psychiatric Disorders

Insomnia

2

 

 

Table 5: Less common (0.1 to <1.0%) adverse reactions reported in active-controlled clinical trials with moxifloxacin (N=14,981)
 

System Organ Class

Adverse Reactions*

Blood and Lymphatic System Disorders

Thrombocythemia

 

Eosinophilia

 

Neutropenia

 

Thrombocytopenia

 

Leucopenia

 

Leucocytosis

Cardiac Disorders

Atrial fibrillation

 

Palpitations

 

Tachycardia

 

Cardiac failure congestive

 

Angina pectoris

 

Cardiac failure

 

Cardiac arrest

 

Bradycardia

Ear and Labyrinth Disorders

Vertigo

 

Tinnitus

Eye Disorders

Vision blurred

Gastrointestinal Disorders

Dry mouth

 

Abdominal discomfort

 

Flatulence

 

Abdominal distention

 

Gastritis

 

Gastro-oesophageal reflux disease

General Disorders and Administration Site Conditions

Fatigue

 

Chest pain

 

Asthenia

 

Ooedema peripheral

 

Pain

 

Malaise

 

Infusion site extravasation

 

Oedema

 

Chills

 

Chest discomfort

 

Facial pain

Hepatobiliary Disorders

Hepatic function abnormal

Infections and Infestations

Vulvovaginal candidiasis

 

Oral candidiasis

 

Vulvovaginal mycotic infection

 

Candidiasis

 

Vaginal infection

 

Oral fungal infection

 

Fungal infection

 

Gastroenteritis

Investigations

Aspartate aminotransferase increased

 

Gamma-glutamyltransferase increased

 

Blood alkaline phosphatase increased

 

Hepatic enzyme increased

 

Electrocardiogram QT prolonged

 

Blood lactate dehydrogenase increased

 

Platelet count increased

 

Blood amylase increased

 

Blood glucose increased

 

Lipase increased

 

Haemoglobin decreased

 

Blood creatinine increased

 

Transaminases increased

 

WBC count increased

 

Blood urea increased

 

Liver function test abnormal

 

Haematocrit decreased

 

Prothrombin time prolonged

 

Eosinophil count increased

 

Activated partial thromboplastin time prolonged

 

Blood bilirubin increased

 

Blood triglycerides increased

 

Blood uric acid increased

 

Blood pressure increased

Metabolism and Nutrition Disorders

Hyperglycaemia

 

Anorexia

 

Hypoglycaemia

 

Hyperlipidaemia

 

Decreased appetite

 

Dehydration

Musculoskeletal and Connective Tissue Disorders

Back pain

 

Pain in extremity

 

Arthralgia

 

Myalgia

 

Muscle spasms

 

Musculoskeletal chest pain

 

Musculoskeletal pain

Nervous System Disorders

Dysgeusia

 

Somnolence

 

Tremor

 

Lethargy

 

Paraesthesia

 

Tension headache

 

Hypoaesthesia

 

Syncope

Psychiatric Disorders

Anxiety

 

Confusional state

 

Agitation

 

Depression

 

Nervousness

 

Restlessness

 

Hallucination

 

Disorientation

Renal and Urinary Disorders

Renal failure

 

Dysuria

 

Renal failure acute

Reproductive System and Breast Disorders

Vulvovaginal pruritus

Respiratory, Thoracic and Mediastinal Disorders

Dyspnea

 

Asthma

 

Wheezing

 

Bronchospasm

Skin and Subcutaneous Tissue Disorders

Rash

 

Pruritus

 

Hyperhidrosis

 

Erythema

 

Urticaria

 

Dermatitis allergic

 

Night sweats

Vascular Disorders

Hypertension

 

Hypotension

 

Phlebitis

*MedDRA Version 12.0

The drug may cause low blood sugar and mental health related side effects. Low blood sugar levels, also called hypoglycemia, can lead to coma. The mental health side effects more prominent and more consistent across the systemic fluoroquinolone drug class are as mentioned below;

  • Disturbances in attention
  • Disorientation
  • Agitation
  • Nervousness
  • Memory impairment

Serious disturbances in mental abilities called delirium

Postmarketing Experience

Below is the list of adverse reactions that have been identified during post-approval use of moxifloxacin. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Table 6: Postmarketing reports of adverse drug reactions
 

System/Organ Class

Adverse Reaction

Blood and Lymphatic System Disorders

Agranulocytosis

Pancytopenia

Cardiac Disorders

Ventricular tachyarrhythmias (including, in very rare cases, cardiac arrest and torsades de pointes, and usually in patients with concurrent severe underlying pro-arrhythmic conditions)

Ear and Labyrinth Disorders

Hearing impairment, including deafness (reversible in the majority of cases)

Eye Disorders

Vision loss (especially in the course of CNS reactions, transient in the majority of cases)

Hepatobiliary Disorders

Hepatitis (predominantly cholestatic)

Hepatic failure (including fatal cases)

Jaundice

Acute hepatic necrosis

Immune System Disorders

Anaphylactic reaction

Anaphylactic shock

Angio-oedema (including laryngeal oedema)

Musculoskeletal and Connective Tissue Disorders

Tendon rupture

Nervous System Disorders

Altered coordination

Abnormal gait

Myasthenia gravis (exacerbation of)

Muscle weakness

Peripheral neuropathy (that may be irreversible) Polyneuropathy

Psychiatric Disorders

Psychotic reaction (very rarely culminating in self-injurious behaviour, such as suicidal ideation/thoughts or suicide attempts

Renal and Urinary Disorders

Renal dysfunction

Interstitial nephritis

Respiratory, Thoracic and Mediastinal Disorders

Allergic pneumonitis

Skin and Subcutaneous Tissue Disorders

Photosensitivity/phototoxicity reaction

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Laboratory Changes

Changes in laboratory parameters, without regard to drug relationship, which are not listed above and which occurred in ≥2% of patients and at an incidence greater than in controls, included the following: increases in MCH, neutrophils, WBCs, PT ratio, ionized calcium, chloride, albumin, globulin, bilirubin; decreases in haemoglobin, RBCs, neutrophils, eosinophils, basophils, PT ratio, glucose, PO2, bilirubin and amylase. It cannot be determined if any of the above laboratory abnormalities were caused by the drug or the underlying condition being treated.

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 18002677779 (Cipla Number) or you can report to PvPI on 1800 180 3024.

By reporting side-effects, you can help provide more information on the safety of this product.

Overdosage

Single oral overdoses up to 2.8 g were not associated with any serious adverse events. In the event of acute overdose, the stomach should be emptied and adequate hydration maintained. ECG monitoring is recommended due to the possibility of QT interval prolongation. The patient should be carefully observed and given supportive treatment. The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase of systemic moxifloxacin exposure. About 3% and 9% of the dose of moxifloxacin, as well as about 2% and 4.5% of its glucuronide metabolite are removed by continuous ambulatory peritoneal dialysis and haemodialysis, respectively.

Single oral moxifloxacin doses of 2,000, 500, and 1,500 mg/kg were lethal to rats, mice, and cynomolgus monkeys, respectively. The minimum lethal I.V. dose in mice and rats was 100 mg/kg. Toxic signs after administration of a single high dose of moxifloxacin to these animals included CNS and gastrointestinal effects such as decreased activity, somnolence, tremor, convulsions, vomiting and diarrhoea.

Storage and Handling Instructions

Store in a cool dry place. Protect from light

Packaging Information

MOXICIP: Blister pack of 5 tablets

Last Updated: Nov 2018
Last Reviewed: Nov 2018