MOXIFLOXACIN HYDROCHLORIDE tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

MOXIFLOXACIN HYDROCHLORIDE (UNII: C53598599T) (MOXIFLOXACIN - UNII:U188XYD42P)

Available from:

Aurobindo Pharma Limited

INN (International Name):

MOXIFLOXACIN HYDROCHLORIDE

Composition:

MOXIFLOXACIN 400 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Moxifloxacin tablets are indicated in adult patients for the treatment of Community Acquired Pneumonia caused by susceptible isolates of Streptococcus pneumoniae (including multi-drug resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Clinical Studies (14.3)] . MDRSP isolates are isolates resistant to two or more of the following antibacterial drugs: penicillin (minimum inhibitory concentrations [MIC] ≥ 2 mcg/mL), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Moxifloxacin tablets are indicated in adult patients for the treatment of Uncomplicated Skin and Skin Structure Infections caused by susceptible isolates of methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes [see Clinical Studies (14.4)]. Moxifloxacin tablets are indicated in adult patients for the treatment of Complicated Skin and Skin Structure Infections caused by susceptible isolates of methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae [see Clinical Studies (14.5)]. Moxifloxacin tablets are indicated in adult patients for the treatment of Complicated Intra-Abdominal Infections (cIAI) including polymicrobial infections such as abscess caused by susceptible isolates of Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species [see Clinical Studies (14.6)] . Moxifloxacin tablets are indicated in adult patients for the treatment of plague, including pneumonic and septicemic plague, due to susceptible isolates of Yersinia pestis and prophylaxis of plague in adult patients. Efficacy studies of moxifloxacin could not be conducted in humans with plague for feasibility reasons. Therefore, this indication is based on an efficacy study conducted in animals only [see Clinical Studies (14.7)] . Moxifloxacin tablets are indicated in adult patients for the treatment of acute bacterial sinusitis (ABS) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae , or Moraxella catarrhalis [see Clinical Studies (14.1)] . Because fluoroquinolones, including moxifloxacin tablets, have been associated with serious adverse reactions [see  Warnings and Precautions (5.1 to 5.14)] and for some patients ABS is self-limiting, reserve moxifloxacin tablets for treatment of ABS in patients who have no alternative treatment options. Moxifloxacin tablets are indicated in adult patients for the treatment of Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus, or Moraxella catarrhalis [see Clinical Studies (14.2)]. Because fluoroquinolones, including moxifloxacin tablets, have been associated with serious adverse reactions [see Warnings and Precautions (5.1 to 5.14)] and for some patients ABECB is self-limiting, reserve moxifloxacin tablets for treatment of ABECB in patients who have no alternative treatment options. To reduce the development of drug-resistant bacteria and maintain the effectiveness of moxifloxacin tablets and other antibacterial drugs, moxifloxacin 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. Moxifloxacin tablets are contraindicated in persons with a history of hypersensitivity to moxifloxacin or any member of the quinolone class of antibacterials [see Warnings and Precautions (5.8)] . 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 hydrochloride may cause fetal harm. Moxifloxacin did not cause fetal malformations when administered to pregnant rats (IV and oral), rabbits (IV), and monkeys (oral) at exposures that were 0.24 to 2.5 times of those at the human clinical dose (400 mg/day moxifloxacin hydrochloride). 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 estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.   Data Animal Data Animal reproductive and development studies were done in rats, rabbits and cynomolgus macaques. Moxifloxacin did not cause fetal malformations 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). Fetal malformations were not observed at intravenous doses as high as 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) in litters of pregnant rats that received moxifloxacin 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. Fetal malformations were not observed 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. 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). When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for moxifloxacin hydrochloride and any potential adverse effects on the breastfed child from moxifloxacin hydrochloride 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. Effectiveness in pediatric patients and adolescents less than 18 years of age has not been established. Moxifloxacin hydrochloride causes arthropathy in juvenile animals. Limited information on the safety of moxifloxacin hydrochloride in 301 pediatric patients is available from the cIAI trial [see Boxed Warning, Warnings and Precautions (5.11) and Nonclinical Toxicology (13.2)]. Active Controlled Trial in Complicated Intra-Abdominal Infection (cIAI) The safety and efficacy of moxifloxacin hydrochloride 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 hydrochloride 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 hydrochloride, 15 were below the age of 6 years and 286 were between the ages of 6 to <18 years. Patients received sequential intravenous/oral moxifloxacin hydrochloride 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 hydrochloride 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 hydrochloride-treated patients versus 1.3% (2/150) of comparator-treated patients. The adverse reaction profile of moxifloxacin hydrochloride 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 hydrochloride-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 [see Warnings and Precautions (5.11) and Nonclinical Toxicology (13.2)].  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 hydrochloride and 95.5% (127/133) for comparator; see Table 6. Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as moxifloxacin hydrochloride. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles, 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 hydrochloride to elderly patients especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue moxifloxacin tablets and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see Boxed Warning, and Warnings and Precautions (5.2)]. Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see Warnings and Precautions (5.9) ]. In controlled multiple-dose clinical trials, 23% of patients receiving oral moxifloxacin hydrochloride were greater than or equal to 65 years of age and 9% were greater than or equal to 75 years of age. The clinical trial data demonstrate that there is no difference in the safety and efficacy of oral moxifloxacin hydrochloride in patients aged 65 or older compared to younger adults. In trials of intravenous use, 42% of moxifloxacin hydrochloride patients were greater than or equal to 65 years of age, and 23% were greater than or equal to 75 years of age. The clinical trial data demonstrate that the safety of intravenous moxifloxacin hydrochloride in patients aged 65 or older was similar to that of comparator-treated patients. In general, elderly patients may be more susceptible to drug-associated effects of the QT interval. Therefore, moxifloxacin hydrochloride should be avoided in patients taking drugs that can result in prolongation of the QT interval (for example, class IA or class III antiarrhythmics) or in patients with risk factors for torsade de pointes (for example, known QT prolongation, uncorrected hypokalemia) [see Warnings and Precautions (5.6) , Drug Interactions (7.5) , and Clinical Pharmacology (12.3) ]. 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) [see Dosage and Administration (2), and Clinical Pharmacology (12.3)]. 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 hydrochloride should be used with caution in these patients [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)] .

Product summary:

Moxifloxacin Tablets, USP are available as modified capsule shaped, dull red film-coated tablets containing 400 mg moxifloxacin. The tablet is debossed with E-18 on one side and plain on the other side.                   Bottles of 30                                                         NDC 65862-603-30                   Bottles of 1,000                                                    NDC 65862-603-99                   Cartons of 50 (5 x 10) Unit-dose Tablets              NDC 65862-603-55 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Avoid high humidity.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

MOXIFLOXACIN HYDROCHLORIDE - MOXIFLOXACIN HYDROCHLORIDE TABLET, FILM
COATED
Aurobindo Pharma Limited
----------
MEDICATION GUIDE
Moxifloxacin Tablets, USP
(mox'' i flox' a sin)
for oral use
Rx only
Read the Medication Guide that comes with moxifloxacin tablets before
you start taking them and each
time you get a refill. There may be new information. This Medication
Guide does not take the place of
talking to your healthcare provider about your medical condition or
your treatment.
What is the most important information I should know about
moxifloxacin tablets?
Moxifloxacin tablets is in a class of antibiotics called
fluoroquinolones. Moxifloxacin tablets can cause
serious side effects that can happen at the same time and could result
in death. If you get any of the
following serious side effects, you should stop taking moxifloxacin
tablets and get medical help right
away. Talk with your healthcare provider about whether you should
continue to take moxifloxacin tablets.
1. Tendon rupture or swelling of the tendon (tendinitis).
•
Tendon problems can happen in people of all ages who take moxifloxacin
tablets. Tendons are
tough cords of tissue that connect muscles to bones. Symptoms of
tendon problems may include:
•
Pain, swelling, tears and inflammation of tendons including the back
of the ankle
(Achilles), shoulder, hand, or other tendon sites.
•
The risk of getting tendon problems while you take moxifloxacin
tablets is higher if you:
•
Are over 60 years of age.
•
Are taking steroids (corticosteroids).
•
Have had a kidney, heart or lung transplant.
•
Tendon problems can happen in people who do not have the above risk
factors when they
take moxifloxacin tablets.
•
Other reasons that can increase your risk of tendon problems can
include:
•
Physical activity or exercise.
•
Kidney failure.
•
Tendon problems in the past, such as in people with rheumatoid
arthritis (RA).
•
Stop taking moxifloxacin tablets immediately and call your healthcare
provider right away at the
first sign of tendon pain, swe

Summary of Product characteristics

MOXIFLOXACIN HYDROCHLORIDE - MOXIFLOXACIN HYDROCHLORIDE TABLET, FILM
COATED
AUROBINDO PHARMA LIMITED
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
MOXIFLOXACIN TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
MOXIFLOXACIN TABLETS.
MOXIFLOXACIN TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1999
WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON
RUPTURE,
PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS AND EXACERBATION
OF MYASTHENIA GRAVIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_
FLUOROQUINOLONES, INCLUDING MOXIFLOXACIN HYDROCHLORIDE, HAVE BEEN
ASSOCIATED WITH
DISABLING AND POTENTIALLY IRREVERSIBLE SERIOUS ADVERSE REACTIONS THAT
HAVE OCCURRED
TOGETHER (5.1) INCLUDING:
TENDINITIS AND TENDON RUPTURE (5.2)
PERIPHERAL NEUROPATHY (5.3)
CENTRAL NERVOUS SYSTEM EFFECTS (5.4)
DISCONTINUE MOXIFLOXACIN HYDROCHLORIDE IMMEDIATELY AND AVOID THE USE
OF
FLUOROQUINOLONES, INCLUDING MOXIFLOXACIN HYDROCHLORIDE, IN PATIENTS
WHO EXPERIENCE ANY
OF THESE SERIOUS ADVERSE REACTIONS (5.1)
FLUOROQUINOLONES, INCLUDING MOXIFLOXACIN HYDROCHLORIDE, MAY EXACERBATE
MUSCLE
WEAKNESS IN PATIENTS WITH MYASTHENIA GRAVIS. AVOID MOXIFLOXACIN
HYDROCHLORIDE IN
PATIENTS WITH KNOWN HISTORY OF MYASTHENIA GRAVIS (5.5).
BECAUSE FLUOROQUINOLONES, INCLUDING MOXIFLOXACIN HYDROCHLORIDE, HAVE
BEEN
ASSOCIATED WITH SERIOUS ADVERSE REACTIONS (5.1 TO 5.14), RESERVE
MOXIFLOXACIN
HYDROCHLORIDE FOR USE IN PATIENTS WHO HAVE NO ALTERNATIVE TREATMENT
OPTIONS FOR THE
FOLLOWING INDICATIONS:
ACUTE BACTERIAL SINUSITIS (1.6)
ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS (1.7)
RECENT MAJOR CHANGES
Dosage and Administration (2.2) 5/2020
INDICATIONS AND USAGE
Moxifloxacin tablets are a fluoroquinolone antibacterial indicated for
treating infections in adults 18 years
of age and older caused by designated susceptible bacteria, in the
conditions listed below:
Community Acquired Pneumonia (1.1)
Skin and Skin Structure Infections: Uncomplicated (1.2) and
Com