1. Name of The Medicinal Product

Moxifloxacin 400mg Tablets USP Taj Pharma

  1. Qualitative and Quantitative Composition

Each film-coated tablet contains:
Moxifloxacin Hydrochloride USP
Equivalent to Moxifloxacin   400mg
Colours: Red Oxide of Iron & Titanium Dioxide

For the full list of excipients, see section 6.1.

  1. Pharmaceutical Form

Film-coated tablet

  1. Clinical Particulars

4.1 Therapeutic indications

Moxifloxacin 400 mg film-coated tablets are indicated for the treatment of the following bacterial infections in patients of 18 years and older caused by bacteria susceptible to moxifloxacin (see sections 4.4, 4.8 and 5.1).

In the following indications, Moxifloxacin should be used only when it is considered inappropriate to use other antibacterial agents that are commonly recommended for the treatment of these infections:

– Acute bacterial sinusitis

– Acute exacerbation of chronic obstructive pulmonary disease including bronchitis

In the following indications, Moxifloxacin should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of these infections or when these have failed:

– Community acquired pneumonia, except severe cases

– Mild to moderate pelvic inflammatory disease (i.e. infections of female upper genital tract, including salpingitis and endometritis), without an associated tubo-ovarian or pelvic abscess.

Moxifloxacin 400 mg film-coated tablets are not recommended for use in monotherapy of mild to moderate pelvic inflammatory disease but should be given in combination with another appropriate antibacterial agent (e.g. a cephalosporin) due to increasing moxifloxacin resistance of Neisseria gonorrhoeae unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded (see sections 4.4 and 5.1).

Moxifloxacin 400 mg film-coated tablets may also be used to complete a course of therapy in patients who have shown improvement during initial treatment with intravenous moxifloxacin for the following indications:

– Community-acquired pneumonia

– Complicated skin and skin structure infections

Moxifloxacin 400 mg film-coated tablets should not be used to initiate therapy for any type of skin and skin structure infection or in severe community-acquired pneumonia.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Posology (adults)

The recommended dose is one 400 mg film-coated tablet once daily.

Renal/hepatic impairment

No adjustment of dosage is required in patients with mild to severely impaired renal function or in patients on chronic dialysis i.e. haemodialysis and continuous ambulatory peritoneal dialysis (see section 5.2 for more details).

There is insufficient data in patients with impaired liver function (see section 4.3).

Other special populations

No adjustment of dosage is required in the elderly and in patients with low bodyweight.

Paediatric population

Moxifloxacin is contraindicated in children and adolescents (< 18 years). Efficacy and safety of moxifloxacin in children and adolescents have not been established (see section 4.3).

Method of administration

The film-coated tablet should be swallowed whole with sufficient liquid and may be taken independent of meals.

Duration of administration

Moxifloxacin 400 mg film-coated tablets should be used for the following treatment durations:

– Acute exacerbation of chronic obstructive pulmonary disease including bronchitis5 – 10 days
– Community acquired pneumonia10 days
– Acute bacterial sinusitis7 days
– Mild to moderate pelvic inflammatory disease14 days

Moxifloxacin 400 mg film-coated tablets have been studied in clinical trials for up to 14 days treatment.

Sequential (intravenous followed by oral) therapy

In clinical studies with sequential therapy most patients switched from intravenous to oral therapy within 4 days (community-acquired pneumonia) or 6 days (complicated skin and skin structure infections). The recommended total duration of intravenous and oral treatment is 7 -14 days for community-acquired pneumonia and 7 – 21 days for complicated skin and skin structure infections

The recommended dose (400 mg once daily) and duration of therapy for the indication being treated should not be exceeded.

4.3 Contraindications

– Hypersensitivity to moxifloxacin, other quinolones or to any of the excipients listed in section 6.1.

– Pregnancy and lactation (see section 4.6).

– Patients below 18 years of age.

– Patients with a history of tendon disease/disorder related to quinolone treatment.

Both in preclinical investigations and in humans, changes in cardiac electrophysiology have been observed following exposure to moxifloxacin, in the form of QT prolongation. For reasons of drug safety, moxifloxacin is therefore contraindicated in patients with:

– Congenital or documented acquired QT prolongation

– Electrolyte disturbances, particularly in uncorrected hypokalaemia

– Clinically relevant bradycardia

– Clinically relevant heart failure with reduced left-ventricular ejection fraction

– Previous history of symptomatic arrhythmias

Moxifloxacin should not be used concurrently with other drugs that prolong the QT interval (see also section 4.5).

Due to limited clinical data, moxifloxacin is also contraindicated in patients with impaired liver function (Child Pugh C) and in patients with transaminases increase > 5fold ULN.

4.4 Special warnings and precautions for use

The use of moxifloxacin should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products (see section 4.8). Treatment of these patients with moxifloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see also section 4.3).

The benefit of moxifloxacin treatment especially in infections with a low degree of severity should be balanced with the information contained in the warnings and precautions section.

Prolongation of QTc interval and potentially QTc-prolongation-related clinical conditions

Moxifloxacin has been shown to prolong the QTc interval on the electrocardiogram in some patients. In the analysis of ECGs obtained in the clinical trial program, QTc prolongation with moxifloxacin was 6 msec ± 26 msec, 1.4% compared to baseline. As women tend to have a longer baseline QTc interval compared with men, they may be more sensitive to QTc-prolonging medications. Elderly patients may also be more susceptible to drug-associated effects on the QT interval.

Medication that can reduce potassium levels should be used with caution in patients receiving moxifloxacin (see also sections 4.3 and 4.5).

Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients), such as acute myocardial ischaemia or QT prolongation as this may lead to an increased risk for ventricular arrhythmias (incl. torsade de pointes) and cardiac arrest (see also section 4.3). The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded.

If signs of cardiac arrhythmia occur during treatment with moxifloxacin, treatment should be stopped and an ECG should be performed.

Hypersensitivity/allergic reactions

Hypersensitivity and allergic reactions have been reported for fluoroquinolones including moxifloxacin after first administration. Anaphylactic reactions can progress to a life-threatening shock, even after the first administration. In cases of clinical manifestations of severe hypersensitivity reactions moxifloxacin should be discontinued and suitable treatment (e.g. treatment for shock) initiated.

Severe liver disorders

Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with moxifloxacin (see section 4.8). Patients should be advised to contact their doctor prior to continuing treatment if signs and symptoms of fulminant hepatic disease develop such as rapidly developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy.

Liver function tests/investigations should be performed in cases where indications of liver dysfunction occur.

Serious bullous skin reactions

Cases of bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with moxifloxacin (see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.

Patients predisposed to seizures

Quinolones are known to trigger seizures. Use should be with caution in patients with CNS disorders or in the presence of other risk factors which may predispose to seizures or lower the seizure threshold. In case of seizures, treatment with moxifloxacin should be discontinued and appropriate measures instituted.

Prolonged, disabling and potentially irreversible serious adverse drug reactions

Very rare cases of prolonged (continuing months or years), disabling and potentially irreversible serious adverse drug reactions affecting different, sometimes multiple, body systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors. Moxifloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to contact their prescriber for advice.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia, hypoaesthesia, dysaesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. 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 in order to prevent the development of potentially irreversible condition (see section 4.8).

Psychiatric reactions

Psychiatric reactions may occur even after the first administration of quinolones, including moxifloxacin. In very rare cases depression or psychotic reactions have progressed to suicidal thoughts and self-injurious behaviour such as suicide attempts (see section 4.8). In the event that the patient develops these reactions, moxifloxacin should be discontinued and appropriate measures instituted. Caution is recommended if moxifloxacin is to be used in psychotic patients or in patients with history of psychiatric disease.

Antibiotic-associated diarrhoea incl. colitis

Antibiotic-associated diarrhoea (AAD) and antibiotic-associated colitis (AAC), including pseudomembranous colitis and Clostridium difficile-associated diarrhoea, has been reported in association with the use of broad spectrum antibiotics including moxifloxacin and may range in severity from mild diarrhoea to fatal colitis. Therefore it is important to consider this diagnosis in patients who develop serious diarrhoea during or after the use of moxifloxacin. If AAD or AAC is suspected or confirmed, ongoing treatment with antibacterial agents, including moxifloxacin, should be discontinued and adequate therapeutic measures should be initiated immediately. Furthermore, appropriate infection control measures should be undertaken to reduce the risk of transmission. Drugs inhibiting peristalsis are contraindicated in patients who develop serious diarrhoea.

Patients with myasthenia gravis

Moxifloxacin should be used with caution in patients with myasthenia gravis because the symptoms can be exacerbated.

Tendinitis and tendon rupture

Tendinitis and tendon rupture (especially but not limited to Achilles tendon), sometimes bilateral, may occur as early as within 48 hours of starting treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment (see sections 4.3 and 4.8). The risk of tendinitis and tendon rupture is increased in older patients, patients with renal impairment, patients with solid organ transplants, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.

At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with moxifloxacin should be discontinued and alternative treatment should be considered. The affected limb(s) should be appropriately treated (e.g. immobilisation). Corticosteroids should not be used if signs of tendinopathy occur.

Aortic aneurysm and dissection

Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the older population. Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or dissection, or in presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet´s disease, hypertension, known atherosclerosis). In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.

Patients with renal impairment

Elderly patients with renal disorders should use moxifloxacin with caution if they are unable to maintain adequate fluid intake, because dehydration may increase the risk of renal failure.

Vision disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately (see sections 4.7 and 4.8).

Dysglycemia

As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin (see section 4.8). In moxifloxacin-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g. sulfonylurea) or with insulin. Cases of hypoglycaemic coma have been reported. In diabetic patients, careful monitoring of blood glucose is recommended.

Prevention of photosensitivity reactions

Quinolones have been shown to cause photosensitivity reactions in patients. However, studies have shown that moxifloxacin has a lower risk to induce photosensitivity. Nevertheless patients should be advised to avoid exposure to either UV irradiation or extensive and/or strong sunlight during treatment with moxifloxacin.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with a family history of, or actual glucose-6-phosphate dehydrogenase deficiency are prone to haemolytic reactions when treated with quinolones. Therefore, moxifloxacin should be used with caution in these patients.

Patients with pelvic inflammatory disease

For patients with complicated pelvic inflammatory disease (e.g. associated with a tubo-ovarian or pelvic abscess), for whom an intravenous treatment is considered necessary, treatment with Moxifloxacin 400 mg film-coated tablets is not recommended.

Pelvic inflammatory disease may be caused by fluoroquinolone-resistant Neisseria gonorrhoeae. Therefore in such cases empirical moxifloxacin should be co-administered with another appropriate antibiotic (e.g. a cephalosporin) unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded. If clinical improvement is not achieved after 3 days of treatment, the therapy should be reconsidered.

Patients with special cSSSI

Clinical efficacy of intravenous moxifloxacin in the treatment of severe burn infections, fasciitis and diabetic foot infections with osteomyelitis has not been established.

Interference with biological tests

Moxifloxacin therapy may interfere with the Mycobacterium spp. culture test by suppression of mycobacterial growth causing false negative results in samples taken from patients currently receiving moxifloxacin.

Patients with MRSA infections

Moxifloxacin is not recommended for the treatment of MRSA infections. In case of a suspected or confirmed infection due to MRSA, treatment with an appropriate antibacterial agent should be started (see section 5.1).

Paediatric population

Due to adverse effects on the cartilage in juvenile animals (see section 5.3) the use of moxifloxacin in children and adolescents < 18 years is contraindicated (see section 4.3).

Information about excipients

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially “sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

Interactions with medicinal products

An additive effect on QT interval prolongation of moxifloxacin and other medicinal products that may prolong the QTc interval cannot be excluded. This might lead to an increased risk of ventricular arrhythmias, including torsade de pointes. Therefore, co-administration of moxifloxacin with any of the following medicinal products is contraindicated (see also section 4.3):

– anti-arrhythmics class IA (e.g. quinidine, hydroquinidine, disopyramide)

– anti-arrhythmics class III (e.g. amiodarone, sotalol, dofetilide, ibutilide)

– antipsychotics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride)

– tricyclic antidepressive agents

– certain antimicrobial agents (saquinavir, sparfloxacin, erythromycin IV, pentamidine, antimalarials particularly halofantrine)

– certain antihistaminics (terfenadine, astemizole, mizolastine)

– others (cisapride, vincamine IV, bepridil, diphemanil).

Moxifloxacin should be used with caution in patients who are taking medication that can reduce potassium levels (e.g. loop and thiazide-type diuretics, laxatives and enemas [high doses], corticosteroids, amphotericin B) or medication that is associated with clinically significant bradycardia.

An interval of about 6 hours should be left between administration of agents containing bivalent or trivalent cations (e.g. antacids containing magnesium or aluminium, didanosine tablets, sucralfate and agents containing iron or zinc) and administration of moxifloxacin.

Concomitant administration of charcoal with an oral dose of 400 mg moxifloxacin led to a pronounced prevention of drug absorption and a reduced systemic availability of the drug by more than 80%. Therefore, the concomitant use of these two drugs is not recommended (except for overdose cases, see also section 4.9).

After repeated dosing in healthy volunteers, moxifloxacin increased Cmax of digoxin by approximately 30% without affecting AUC or trough levels. No precaution is required for use with digoxin.

In studies conducted in diabetic volunteers, concomitant administration of oral moxifloxacin with glibenclamide resulted in a decrease of approximately 21% in the peak plasma concentrations of glibenclamide. The combination of glibenclamide and moxifloxacin could theoretically result in a mild and transient hyperglycaemia. However, the observed pharmacokinetic changes for glibenclamide did not result in changes of the pharmacodynamic parameters (blood glucose, insulin). Therefore no clinically relevant interaction was observed between moxifloxacin and glibenclamide.

Changes in INR

A large number of cases showing an increase in oral anticoagulant activity have been reported in patients receiving antibacterial agents, especially fluoroquinolones, macrolides, tetracyclines, cotrimoxazole and some cephalosporins. The infectious and inflammatory conditions, age and general status of the patient appear to be risk factors. Under these circumstances, it is difficult to evaluate whether the infection or the treatment caused the INR (international normalised ratio) disorder. A precautionary measure would be to more frequently monitor the INR. If necessary, the oral anticoagulant dosage should be adjusted as appropriate.

Clinical studies have shown no interactions following concomitant administration of moxifloxacin with: ranitidine, probenecid, oral contraceptives, calcium supplements, morphine administered parenterally, theophylline, cyclosporine or itraconazole.

In vitro studies with human cytochrome P450 enzymes supported these findings. Considering these results a metabolic interaction via cytochrome P450 enzymes is unlikely.

Interaction with food

Moxifloxacin has no clinically relevant interaction with food including dairy products.

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of moxifloxacin in human pregnancy has not been evaluated.. Animal studies have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Due to the experimental risk of damage by fluoroquinolones to the weight-bearing cartilage of immature animals and reversible joint injuries described in children receiving some fluoroquinolones, moxifloxacin must not be used in pregnant women (see section 4.3).

Breastfeeding

There is no data available in lactating or nursing women. Preclinical data indicate that small amounts of moxifloxacin are secreted in milk. In the absence of human data and due to the experimental risk of damage by fluoroquinolones to the weight-bearing cartilage of immature animals, breast-feeding is contraindicated during moxifloxacin therapy (see section 4.3).

Fertility

Animal studies do not indicate impairment of fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

No studies on the effects of moxifloxacin on the ability to drive and use machines have been performed. However, fluoroquinolones including moxifloxacin may result in an impairment of the patient’s ability to drive or operate machinery due to CNS reactions (e.g. dizziness; acute, transient loss of vision, see section 4.8) or acute and short lasting loss of consciousness (syncope, see section 4.8). Patients should be advised to see how they react to moxifloxacin before driving or operating machinery.

4.8 Undesirable effects

Adverse reactions based on all clinical trials and derived from post-marketing reports with moxifloxacin 400 mg (oral and sequential therapy) sorted by frequencies are listed below:

Apart from nausea and diarrhoea all adverse reactions were observed at frequencies below 3%.

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)

System Organ Class (MedDRA)CommonUncommonRareVery Rare
Infections and infestationsSuperinfections due to resistant bacteria or fungi e.g. oral and vaginal candidiasis
Blood and lymphatic system disordersAnaemia

Leucopenia(s)

Neutropenia

Thrombocytopenia

Thrombocythemia

Blood eosinophilia

Prothrombin time prolonged/INR increased

Prothrombin level increased/INR decreased

Agranulocytosis

Immune system disordersAllergic reaction (see section 4.4)Anaphylaxis incl. very rarely life-threatening shock (see section 4.4)

Allergic oedema / angiooedema (incl. laryngeal oedema, potentially life-threatening, see section 4.4)

Metabolism and nutrition disordersHyperlipidemiaHyperglycemia

Hyperuricemia

Hypoglycemia
Psychiatric disorders*Anxiety reactions

Psychomotor hyperactivity/ agitation

Emotional lability

Depression (in very rare cases potentially culminating in self-injurious behaviour, such as suicidal ideations/ thoughts, or suicide attempts, see section 4.4)

Hallucination

Depersonalization

Psychotic reactions (potentially culminating in self- injurious behaviour, such as suicidal ideations/ thoughts, or suicide attempts, see section 4.4)

Nervous system disorders*Headache

Dizziness

Par- and Dysaesthesia

Taste disorders (incl. ageusia in very rare cases)

Confusion and disorientation

Sleep disorders (predominantly insomnia)

Tremor

Vertigo

Somnolence

Hypoaesthesia

Smell disorders (incl. anosmia)

Abnormal dreams

Disturbed coordination (incl. gait disturbances, esp. due to dizziness or vertigo)

Seizures incl. grand mal convulsions (see section 4.4)

Disturbed attention

Speech disorders

Amnesia

Peripheral neuropathy and polyneuropathy

Hyperaesthesia
Eye disorders*Visual disturbances incl. diplopia and blurred vision (especially in the course of CNS reactions, see section 4.4)PhotophobiaTransient loss of vision (especially in the course of CNS reactions, see sections 4.4 and 4.7)

Uveitis and bilateral acute iris transillumination (see section 4.4)

Ear and labyrinth disorders*Tinnitus

Hearing impairment incl. deafness (usually reversible)

Cardiac disordersQT prolongation in patients with hypokalaemia (see sections 4.3 and 4.4)QT prolongation (see section 4.4)

Palpitations

Tachycardia

Atrial fibrillation

Angina pectoris

Ventricular tachyarrhythmias

Syncope (i.e., acute and short lasting loss of consciousness)

Unspecified arrhythmias

Torsade de Pointes (see section 4.4)

Cardiac arrest (see section 4.4)

Vascular disordersVasodilatationHypertension

Hypotension

Vasculitis
Respiratory, thoracic and mediastinal disordersDyspnea (including asthmatic conditions)
Gastrointestinal disordersNausea

Vomiting

Gastrointestinal and abdominal pains

Diarrhoea

Decreased appetite and food intake

Constipation

Dyspepsia

Flatulence

Gastritis

Increased amylase

Dysphagia

Stomatitis

Antibiotic associated colitis (incl. pseudo-membranous colitis, in very rare cases associated with life-threatening complications, see section 4.4)

Hepatobiliary disordersIncrease in transaminasesHepatic impairment (incl. LDH increase)

Increased bilirubin

Increased gamma-glutamyl-transferase

Increase in blood alkaline phosphatase

Jaundice

Hepatitis (predominantly cholestatic)

Fulminant hepatitis potentially leading to life-threatening liver failure (incl. fatal cases, see section 4.4)
Skin and subcutaneous tissue disordersPruritus

Rash

Urticaria

Dry skin

Bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening, see section 4.4)
Musculoskeletal and connective tissue disorders*Arthralgia

Myalgia

Tendonitis (see section 4.4)

Muscle cramp

Muscle twitching

Muscle weakness

Tendon rupture (see section 4.4)

Arthritis

Muscle rigidity

Exacerbation of symptoms of myasthenia gravis (see section 4.4)

Renal and urinary disordersDehydrationRenal impairment (incl. increase in BUN and creatinine)

Renal failure (see section 4.4)

General disorders and administration site conditions*Feeling unwell (predominantly asthenia or fatigue)

Painful conditions (incl. pain in back, chest, pelvic and extremities)

Sweating

Oedema

*Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious drug reactions affecting several, sometimes multiple, system organ classes and senses (including reactions such as tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in some cases irrespective of pre-existing risk factors (see section 4.4).

There have been very rare cases of the following side effects reported following treatment with other fluoroquinolones, which might possibly also occur during treatment with moxifloxacin: increased intracranial pressure (including pseudotumor cerebri), hypernatraemia, hypercalcaemia, haemolytic anaemia, rhabdomyolysis, photosensitivity reactions (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

No specific countermeasures after accidental overdose are recommended. In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Concomitant administration of charcoal with a dose of 400 mg oral moxifloxacin will reduce systemic availability of the drug by more than 80%. The use of charcoal early during absorption may be useful to prevent excessive increase in the systemic exposure to moxifloxacin in cases of oral overdose.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Quinolone antibacterials, fluoroquinolones.

Mechanism of action

Moxifloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative pathogens.

The bactericidal action of moxifloxacin results from the inhibition of both type II topoisomerases (DNA gyrase and topoisomerase IV) required for bacterial DNA replication, transcription and repair. 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.

Pharmacodynamic investigations have demonstrated that moxifloxacin exhibits a concentration dependent killing rate. Minimum bactericidal concentrations (MBC) were found to be in the range of the minimum inhibitory concentrations (MIC).

Effect on the intestinal flora in humans

The following changes in the intestinal flora were seen in volunteers following oral administration of moxifloxacin: Escherichia coliBacillus spp., Enterococcus spp., and Klebsiella spp. were reduced, as were the anaerobes Bacteroides vulgatusBifidobacterium spp., Eubacterium spp., and Peptostreptococcus spp.. For Bacteroides fragilis there was an increase. These changes returned to normal within two weeks.

Mechanism of resistance

Resistance mechanisms that inactivate penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not interfere with the antibacterial activity of moxifloxacin. Other resistance mechanisms such as permeation barriers (common in Pseudomonas aeruginosa) and efflux mechanisms may also effect susceptibility to moxifloxacin.

In vitro resistance to moxifloxacin is acquired through a stepwise process by target site mutations in both type II topoisomerases, DNA gyrase and topoisomerase IV. Moxifloxacin is a poor substrate for active efflux mechanisms in Gram-positive organisms.

Cross-resistance is observed with other fluoroquinolones. However, as moxifloxacin inhibits both topoisomerase II and IV with similar activity in some Gram-positive bacteria, such bacteria may be resistant to other quinolones, but susceptible to moxifloxacin.

Breakpoints

EUCAST clinical MIC and disk diffusion breakpoints for moxifloxacin (01.01.2012):

OrganismSusceptibleResistant
Staphylococcus spp.≤ 0.5 mg/l

≥ 24 mm

> 1 mg/l

< 21 mm

S. pneumoniae≤ 0.5 mg/l

≥ 22 mm

> 0.5 mg/l

< 22 mm

Streptococcus Groups A, B, C, G≤ 0.5 mg/l

≥ 18 mm

> 1 mg/l

< 15 mm

H. influenzae≤ 0.5 mg/l

≥ 25 mm

> 0.5 mg/l

< 25 mm

M. catarrhalis≤ 0.5 mg/l

≥ 23 mm

> 0.5 mg/l

< 23 mm

Enterobacteriaceae≤ 0.5 mg/l

≥ 20 mm

> 1 mg/l

< 17 mm

Non-species related breakpoints*≤ 0.5 mg/l> 1 mg/l
* Non-species related breakpoints have been determined mainly on the basis of pharmacokinetic/pharmacodynamic data and are independent of MIC distributions of specific species. They are for use only for species that have not been given a species-specific breakpoint and are not for use with species where interpretative criteria remain to be determined.

Microbiological Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species and local information of resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought where the local prevalence of resistance is such that utility of the agent in at least some types of infections is questionable.

Commonly susceptible species
Aerobic Gram-positive micro-organisms

Gardnerella vaginalis

Staphylococcus aureus* (methicillin-susceptible)

Streptococcus agalactiae (Group B)

Streptococcus milleri group* (S. anginosus, S. constellatus and S. intermedius)

Streptococcus pneumoniae*

Streptococcus pyogenes* (Group A)

Streptococcus viridans group (S. viridans, S. mutans, S. mitis, S. sanguinis, S. salivarius, S. thermophilus)

Aerobic Gram-negative micro-organisms

Acinetobacter baumanii

Haemophilus influenzae*

Haemophilus parainfluenzae*

Legionella pneumophila

Moraxella (Branhamella) catarrhalis*

Anaerobic micro-organisms

Fusobacterium spp.

Prevotella spp.

“Other” micro-organisms

Chlamydophila (Chlamydia) pneumoniae*

Chlamydia trachomatis*

Coxiella burnetii

Mycoplasma genitalium

Mycoplasma hominis

Mycoplasma pneumoniae*

Species for which acquired resistance may be a problem
Aerobic Gram-positive micro-organisms

Enterococcus faecalis*

Enterococcus faecium*

Staphylococcus aureus (methicillin-resistant)+

Aerobic Gram-negative micro-organisms

Enterobacter cloacae*

Escherichia coli*#

Klebsiella pneumoniae*#

Klebsiella oxytoca

Neisseria gonorrhoeae*+

Proteus mirabilis*

Anaerobic micro-organisms

Bacteroides fragilis*

Peptostreptococcus spp.*

Inherently resistant organisms
Aerobic Gram-negative micro-organisms

Pseudomonas aeruginosa

*Activity has been satisfactorily demonstrated in susceptible strains in clinical studies in the approved clinical indications.

#ESBL-producing strains are commonly resistant to fluoroquinolones

+Resistance rate > 50% in one or more countries

5.2 Pharmacokinetic properties

Absorption and Bioavailability

Following oral administration moxifloxacin is rapidly and almost completely absorbed. The absolute bioavailability amounts to approximately 91%.

Pharmacokinetics are linear in the range of 50 – 800 mg single dose and up to 600 mg once daily dosing over 10 days. Following a 400 mg oral dose peak concentrations of 3.1 mg/l are reached within 0.5 – 4 h post administration. Peak and trough plasma concentrations at steady-state (400 mg once daily) were 3.2 and 0.6 mg/l, respectively. At steady-state the exposure within the dosing interval is approximately 30% higher than after the first dose.

Distribution

Moxifloxacin is distributed to extravascular spaces rapidly; after a dose of 400 mg an AUC of 35 m∙gh/l is observed. The steady-state volume of distribution (Vss) is approximately 2 l/kg. In vitro and ex vivo experiments showed a protein binding of approximately 40 – 42% independent of the concentration of the drug. Moxifloxacin is mainly bound to serum albumin.

The following peak concentrations (geometric mean) were observed following administration of a single oral dose of 400 mg moxifloxacin:

TissueConcentrationSite: Plasma ratio
Plasma3.1 mg/l
Saliva3.6 mg/l0.75 – 1.3
Blister fluid1.61 mg/l1.71
Bronchial mucosa5.4 mg/kg1.7 – 2.1
Alveolar macrophages56.7 mg/kg18.6 – 70.0
Epithelial lining fluid20.7 mg/l5 – 7
Maxillary sinus7.5 mg/kg2.0
Ethmoid sinus8.2 mg/kg2.1
Nasal polyps9.1 mg/kg2.6
Interstitial fluid1.02 mg/l0.8 – 1.42,3
Female genital tract*10.24 mg/kg1.724
* intravenous administration of a single 400 mg dose

1 10 h after administration

2 unbound concentration

3 from 3 h up to 36 h post dose

4 at the end of infusion

Biotransformation

Moxifloxacin undergoes Phase II biotransformation and is excreted via renal and biliary/faecal pathways as unchanged drug as well as in the form of a sulpho-compound (M1) and a glucuronide (M2). M1 and M2 are the only metabolites relevant in humans, both are microbiologically inactive.

In clinical Phase I and in vitro studies no metabolic pharmacokinetic interactions with other drugs undergoing Phase I biotransformation involving cytochrome P450 enzymes were observed. There is no indication of oxidative metabolism.

Elimination

Moxifloxacin is eliminated from plasma with a mean terminal half life of approximately 12 hours. The mean apparent total body clearance following a 400 mg dose ranges from 179 to 246 ml/min. Renal clearance amounted to about 24 – 53 ml/min suggesting partial tubular reabsorption of the drug from the kidneys.

After a 400 mg dose, recovery from urine (approximately 19% for unchanged drug, approximately 2.5% for M1, and approximately 14% for M2) and faeces (approximately 25% of unchanged drug, approximately 36% for M1, and no recovery for M2) totalled to approximately 96%.

Concomitant administration of moxifloxacin with ranitidine or probenecid did not alter renal clearance of the parent drug.

Elderly and patients with low body weight

Higher plasma concentrations are observed in healthy volunteers with low body weight (such as women) and in elderly volunteers.

Renal impairment

The pharmacokinetic properties of moxifloxacin are not significantly different in patients with renal impairment (including creatinine clearance > 20 ml/min/1.73 m2). As renal function decreases, concentrations of the M2 metabolite (glucuronide) increase by up to a factor of 2.5 (with a creatinine clearance of < 30 ml/min/1.73 m2).

Hepatic impairment

On the basis of the pharmacokinetic studies carried out so far in patients with liver failure (Child Pugh A, B), it is not possible to determine whether there are any differences compared with healthy volunteers. Impaired liver function was associated with higher exposure to M1 in plasma, whereas exposure to parent drug was comparable to exposure in healthy volunteers. There is insufficient experience in the clinical use of moxifloxacin in patients with impaired liver function.

5.3 Preclinical safety data

Effects on the haematopoetic system (slight decreases in the number of erythrocytes and platelets) were seen in rats and monkeys. As with other quinolones, hepatotoxicity (elevated liver enzymes and vacuolar degeneration) was seen in rats, monkeys and dogs. In monkeys CNS toxicity (convulsions) occurred. These effects were seen only after treatment with high doses of moxifloxacin or after prolonged treatment.

Moxifloxacin, like other quinolones, was genotoxic in in vitro tests using bacteria or mammalian cells. Since these effects can be explained by an interaction with the gyrase in bacteria and – at higher concentrations – by an interaction with the topoisomerase II in mammalian cells, a threshold concentration for genotoxicity can be assumed. In in vivo tests, no evidence of genotoxicity was found despite the fact that very high moxifloxacin doses were used. Thus, a sufficient margin of safety to the therapeutic dose in man can be provided. Moxifloxacin was non-carcinogenic in an initiation-promotion study in rats.

Many quinolones are photoreactive and can induce phototoxic, photomutagenic and photocarcinogenic effects. In contrast, moxifloxacin was proven to be devoid of phototoxic and photogenotoxic properties when tested in a comprehensive programme of in vitro and in vivo studies. Under the same conditions other quinolones induced effects.

At high concentrations, moxifloxacin is an inhibitor of the rapid component 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 50fold the human dose (> 300 mg/kg), leading to plasma concentrations of ≥ 200 mg/l (more than 40fold the therapeutic level), reversible, non-fatal ventricular arrhythmias were seen.

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 the maximum recommended therapeutic dose of 400 mg (assuming a 50 kg bodyweight) on a mg/kg basis, with plasma concentrations two to three times higher than those at the maximum therapeutic dose.

Toxicity tests in rats and monkeys (repeated dosing up to six months) revealed no indication regarding an oculotoxic risk. In dogs, high oral doses (≥ 60 mg/kg) leading to plasma concentrations ≥ 20 mg/l caused changes in the electroretinogram and in isolated cases an atrophy of the retina.

Reproductive studies performed in rats, rabbits and monkeys indicate that placental transfer of moxifloxacin occurs. Studies in rats (p.o. and i.v.) and monkeys (p.o.) did not show evidence of teratogenicity or impairment of fertility following administration of moxifloxacin. A slightly increased incidence of vertebral and rib malformations was observed in foetuses of rabbits but only at a dose (20 mg/kg i.v.) which was associated with severe maternal toxicity. There was an increase in the incidence of abortions in monkeys and rabbits at human therapeutic plasma concentrations. In rats, decreased foetal weights, an increased prenatal loss, a slightly increased duration of pregnancy and an increased spontaneous activity of some male and female offspring was observed at doses which were 63 times the maximum recommended dose on a mg/kg basis with plasma concentrations in the range of the human therapeutic dose.

  1. Pharmaceutical particulars

6.1 List of excipients

Tablet core: Microcrystalline cellulose, Croscarmellose sodium, Lactose monohydrate & Magnesium stearate.

Film-coat: Hypromellose, Macrogol, Ferric oxide & Titanium dioxide.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Polypropylene/aluminium and polyvinyl chloride/polyvinylidene chloride/aluminium blisters

Do not store above 25°C.

Store in the original package in order to protect from moisture.

Aluminium/aluminium blisters

Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

PVC/Aluminium Blister Pack 10, 20, 30, 40, 50, 60, 90, 100 and 200 Tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com

Moxifloxacin 400mg Tablets USP Taj Pharma

Package leaflet: Information for the patient

(Moxifloxacin)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have more questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

  1. What Moxifloxacin is and what it is used for
    2. What you need to know before you take Moxifloxacin
    3. How to take Moxifloxacin
    4. Possible side effects
    5. How to store Moxifloxacin
    6. Contents of the pack and other information

 

  1. What Moxifloxacin is and what it is used for

Moxifloxacin contains the active substance moxifloxacin, which belongs to a group of antibiotics called fluoroquinolones. Moxifloxacin works by killing bacteria that cause infections.

Moxifloxacin is used in patients aged 18 years and above for treating the following bacterial infections when caused by bacteria against which moxifloxacin is active. Moxifloxacin should only be used to treat these infections when usual antibiotics cannot be used or have not worked:

Infection of the sinuses, sudden worsening of long-term inflammation of the airways or infection of the lungs (pneumonia) acquired outside the hospital (except severe cases).

Mild to moderate infections of the female upper genital tract (pelvic inflammatory disease), including infections of the fallopian tubes and infections of the uterus mucous membrane.

Moxifloxacin tablets are not sufficient on their own for treating this kind of infection. Therefore, another antibiotic in addition to Moxifloxacin tablets should be prescribed by your doctor for the treatment of infections of the female upper genital tract (see section 2What you need to know before you take Moxifloxacin, Warnings and precautions, Talk to your doctor before taking Moxifloxacin).

If the following bacterial infections have shown improvement during initial treatment with Moxifloxacin solution for infusion, Moxifloxacin tablets may also be prescribed by your doctor to complete the course of therapy: Infection of the lungs (pneumonia) acquired outside the hospital, infections of the skin and soft tissue.

Moxifloxacin tablets should not be used to initiate therapy for any type of infections of the skin and soft tissue or in severe infections of the lungs.

  1. What you need to know before you take Moxifloxacin

Contact your doctor if you are not sure if you belong to a patient group described below.

Do not take Moxifloxacin

  • If you are allergic to the active substance moxifloxacin, any other quinolone antibiotics or any of the other ingredients of this medicine (listed in section 6.).
  • If you are pregnant or are breast-feeding.
  • If you are under 18 years of age.
  • If you have previously had problems with your tendons related to treatment with quinolone antibiotics (see section Warnings and Precautionsand section  Possible side effects).
  • If you were born with or have
    • any condition with abnormal heart rhythm (seen on ECG, electrical recording of the heart)
    • a salt imbalance in the blood (especially low levels of potassium or magnesium in the blood)
    • a very slow heart rhythm (called ‘bradycardia’)
    • a weak heart (heart failure)
    • a history of abnormal heart rhythms
      or
    • if you are taking other medicines that result in abnormal ECG changes (see section Other medicines and Moxifloxacin). This is because Moxifloxacin can cause changes on the ECG, that is a prolongation of the QT-interval, i.e., delayed conduction of electrical signals.
  • If you have a severe liver disease or increased liver enzymes (transaminases) higher than 5 times the upper normal limit.

Warnings and precautions

Before taking this medicine

You should not take fluoroquinolone/quinolone antibacterial medicines, including Moxifloxacin, if you have experienced any serious adverse reaction in the past when taking a quinolone or fluoroquinolone. In this situation, you should inform your doctor as soon as possible.

Talk to your doctor before taking Moxifloxacin

  • Moxifloxacin can change your heart’s ECG, especially if you are female, or if you are elderly. If you are currently taking any medicine that decreases your blood potassium levels, consult your doctor before taking Moxifloxacin (see also sections Do not take Moxifloxacinand Other medicines and Moxifloxacin).
  • If you suffer from epilepsyor a condition which makes you likely to have convulsions talk to your doctor before taking Moxifloxacin.
  • If you have or have ever had any mental health problems, consult your doctor before taking Moxifloxacin.
  • If you suffer from myasthenia gravis(abnormal muscle fatigue leading to weakness and in serious cases paralysis), taking Moxifloxacin may worsen the symptoms of your disease. If you think you are affected consult your doctor immediately.
  • If you have been diagnosed with an enlargement or “bulge” of a large blood vessel(aortic aneurysm or large vessel peripheral aneurysm).
  • If you have experienced a previous episode of aortic dissection(a tear in the aorta wall).
  • If you have a family history of aortic aneurysm or aortic dissectionor other risk factors or predisposing conditions (e.g. connective tissue disorders such as Marfan syndrome, or vascular Ehlers-Danlos syndrome, or vascular disorders such as Takayasu arteritis, giant cell arteritis, Behcet´s disease, high blood pressure, or known atherosclerosis).
  • If you or any member of your family have glucose-6-phosphate dehydrogenase deficiency(a rare hereditary disease), tell your doctor, who will advise whether Moxifloxacin is suitable for you.
  • If you have a complicated infection of the female upper genital tract(e.g. associated with an abscess of the fallopian tubes and ovaries or of the pelvis), for which your doctor considers an intravenous treatment necessary, treatment with Moxifloxacin tablets is not appropriate.
  • For the treatment of mild to moderate infections of the female upper genital tractyour doctor should prescribe another antibiotic in addition to Moxifloxacin. If there is no improvement in symptoms after 3 days of treatment, please consult your doctor.

When taking Moxifloxacin

  • If you experience palpitations or irregular heart beatduring the period of treatment, you should inform your doctor immediately. He/she may wish to perform an ECG to measure your heart rhythm.
  • The risk of heart problemsmay increase with increase of the dose. Therefore, the recommended dosage should be followed.
  • There is a rare chance that you may experience a severe, sudden allergic reaction(an anaphylactic reaction/shock) even with the first dose. Symptoms include tightness in the chest, feeling dizzy, feeling sick or faint, or dizziness when standing up. If so, stop taking Moxifloxacin and seek medical advice immediately.
  • Moxifloxacin may cause a rapid and severe inflammation of the liverwhich could lead to life-threatening liver failure (including fatal cases, see section  Possible side effects). If you suddenly feel unwell and/or are being sick and also have yellowing of the whites of the eyes, dark urine, itching of the skin, a tendency to bleed or liver induced disease of the brain (symptoms of a reduced liver function or a rapid and severe inflammation of the liver) please contact your doctor before taking any more tablets.
  • If you develop a skin reaction or blisteringpeeling of the skin and/or mucosal reactions (see section  Possible side effects) contact your doctor immediately before you continue treatment.
  • Quinolone antibiotics, including Moxifloxacin, may cause convulsions. If this happens, stop taking Moxifloxacin and contact your doctor immediately.
  • Prolonged, disabling and potentially irreversible serious side effects.Fluoroquinolone/quinolone antibacterial medicines, including Moxifloxacin, have been associated with very rare but serious side effects, some of them being long lasting (continuing months or years), disabling or potentially irreversible. This includes tendon, muscle and joint pain of the upper and lower limbs, difficulty in walking, abnormal sensations such as pins and needles, tingling, tickling, numbness or burning (paraesthesia), sensory disorders including impairment of vision, taste and smell, and hearing, depression, memory impairment, severe fatigue, and severe sleep disorders.
    If you experience any of these side effects after taking Moxifloxacin, contact your doctor immediately prior to continuing treatment. You and your doctor will decide on continuing the treatment considering also an antibiotic from another class.
  • You may rarely experience symptoms of nerve damage (neuropathy)such as pain, burning, tingling, numbness and/or weakness especially in the feet and legs or hands and arms. If this happens, stop taking Moxifloxacin and inform your doctor immediately in order to prevent the development of potentially irreversible condition.
  • You may experience mental health problemseven when taking quinolone antibiotics, including Moxifloxacin, for the first time. In very rare cases depression or mental health problems have led to suicidal thoughts and self-injurious behaviour such as suicide attempts (see section  Possible side effects). If you develop such reactions, stop taking Moxifloxacin and inform your doctor immediately.
  • You may develop diarrhoeawhilst or after taking antibiotics including Moxifloxacin. If this becomes severe or persistent or you notice that your stool contains blood or mucus you should stop taking Moxifloxacin immediately and consult your doctor. You should not take medicines that stop or slow down bowel movement.
  • Pain and swelling in the joints and inflammation or rupture of tendonsmay occur rarely (see sections Do not take Moxifloxacin and  Possible side effects). Your risk is increased if you are elderly (above 60 years of age), have received an organ transplant, have kidney problems or if you are also taking corticosteroids. Inflammation and ruptures of tendons may occur within the first 48 hours of treatment and even up to several months after stopping of Moxifloxacin therapy. At the first sign of pain or inflammation of a tendon (for example in your ankle, wrist, elbow, shoulder or knee), stop taking Moxifloxacin, contact your doctor and rest the painful area. Avoid any unnecessary exercise as this might increase the risk of a tendon rupture.
  • If you feel sudden, severe pain in your abdomen, chest or back, go immediately to an emergency room.
  • If you are elderly and have kidney problemsmake sure that you drink plenty whilst taking Moxifloxacin. If you get dehydrated this may increase the risk of kidney failure.
  • If your eyesight becomes impairedor if your eyes seem to be otherwise affected, consult an eye specialist immediately (see sections Driving and using machines and  Possible side effects).
  • Fluoroquinolone antibiotics may cause disturbances in blood sugar, including both a decrease in blood sugar below normal levels (hypoglycemia) and an increase in blood sugar above normal levels (hyperglycemia) (see section  Possible side effects). In patients treated with Moxifloxacin, disturbances in blood sugar occurred predominantly in elderly diabetic patients receiving concomitant treatment with oral antidiabetic medicines that lower blood sugar (e. g. sulfonylurea) or with insulin. Loss of consciousness due to severe reduction in blood sugar (hypoglycaemic coma) have been reported. If you suffer from diabetes, your blood sugar should be carefully monitored.
  • Quinolone antibiotics may make your skinbecome more sensitive to sunlight or UV light. You should avoid prolonged exposure to sunlight or strong sunlight and should not use a sunbed or any other UV lamp while taking Moxifloxacin.
  • The efficacy of Moxifloxacin in the treatment of severe burns, infections of deep tissue and diabetic foot infections with osteomyelitis (infections of the bone marrow) has not been established.

Children and adolescents

Do not give this medicine to children and adolescents under the age of 18 because efficacy and safety have not been established for this age group (see section Do not take Moxifloxacin).

Other medicines and Moxifloxacin

Tell your doctor or pharmacist about any other medicines that you are taking, took recently or might take.

For Moxifloxacin, be aware of the following:

  • If you are taking Moxifloxacin and other medicines that affect your heartthere is an increased risk for altering your heart rhythm. Therefore, do not take Moxifloxacin together with the following medicines:
    • medicines that belong to the group of anti-arrhythmics (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide)
    • antipsychotics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride)
    • tricyclic antidepressants
    • some antimicrobials (e.g. saquinavir, sparfloxacin, intravenous erythromycin, pentamidine, antimalarials particularly halofantrine)
    • some antihistamines (e.g. terfenadine, astemizole, mizolastine)
    • other medicines (e.g. cisapride, intravenous vincamine, bepridil and diphemanil).
  • You must tell your doctor if you are taking other medicines that can lower your blood potassium levels (e.g. some diuretics, some laxatives and enemas [high doses] or corticosteroids [anti-inflammatory drugs], amphotericin B) or cause a slow heart rate because these can also increase the risk of serious heart rhythm disturbances while taking Moxifloxacin.
  • Any medicine containing magnesium or aluminium(such as antacids for indigestion), iron, zinc or didanosine or any medicine containing sucralfate (to treat stomach disorders) can reduce the action of Moxifloxacin tablets. Take your Moxifloxacin tablet 6 hours before or after taking the other medicine.
  • Taking any medicine containing charcoalat the same time as Moxifloxacin tablets reduces the action of Moxifloxacin. It is recommended that these medicines are not used together.
  • If you are currently taking drugs to thin your blood(oral anti-coagulants such as warfarin), it may be necessary for your doctor to monitor your blood clotting time.

Moxifloxacin with food and drink

Moxifloxacin can be taken with or without food (including dairy products).

Pregnancy, breast-feeding and fertility

Do not take Moxifloxacin if you are pregnant or breast-feeding.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Animal studies do not indicate that your fertility will be impaired by taking this medicine.

Driving and using machines

Moxifloxacin may make you feel dizzy or light-headed, you may experience a sudden, transient loss of vision, or you may faint for a short period. If you are affected do not drive or operate machinery.

Moxifloxacin contains lactose and sodium

If you have been told by your doctor that you have an intolerance to some sugars, speak to your doctor before taking Moxifloxacin.

This medicine contains less than 1 millimol sodium (23 milligramm) per film-coated tablet, that is to say essentially “sodium-free”.

  1. How to take Moxifloxacin

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose for adults is one 400mg film-coated tablet once daily.

Moxifloxacin tablets are for oral use. Swallow the tablet whole (to mask the bitter taste) and with plenty of liquid. You can take Moxifloxacin with or without food. Try to take the tablet at approximately the same time each day.

The same dose can be taken by elderly patients, patients with a low bodyweight or in patients with kidney problems.

The time you will take Moxifloxacin for depends on your infection. Unless your doctor tells you otherwise, your treatment will be as follows:

  • for sudden worsening of chronic bronchitis (acute exacerbation of chronic obstructive pulmonary disease including bronchitis) 5 – 10 days
  • for infection of the lungs (pneumonia) except for pneumonia which starts during a stay in hospital 10 days
  • for acute infection of the sinuses (acute bacterial sinusitis) 7 days
  • Mild to moderate infections of the female upper genital tract (pelvic inflammatory disease), including infection of the fallopian tubes and infection of the uterus mucous membrane 14 days

When Moxifloxacin film-coated tablets are used to complete a course of therapy started with Moxifloxacin solution for infusion, the recommended durations of use are:

  • Infection of the lungs (pneumonia) acquired outside the hospital 7 -14 days
    Most patients with pneumonia were switched to oral treatment with Moxifloxacin film-coated tablets within 4 days.
  • Infections of the skin and soft tissue 7 -21 days
    Most patients with infections of the skin and soft tissue were switched to oral treatment with Moxifloxacin film-coated tablets within 6 days.

It is important that you complete the course of treatment even if you begin to feel better after a few days. If you stop taking Moxifloxacin too soon your infection may not be completely cured and the infection may return or your condition may get worse. The bacteria causing your infection may become resistant to Moxifloxacin.

The recommended dose and duration of treatment should not be exceeded (see section 2What you need to know before you take Moxifloxacin, Warnings and precautions).

If you take more Moxifloxacin than you should

If you take more than the prescribed one tablet a day, get medical help immediately. Try to take any remaining tablets, the packaging or this leaflet with you to show the doctor or pharmacist what you have taken.

If you forget to take Moxifloxacin

If you forget to take your tablet you should take it as soon as you remember on the same day. If you do not remember on the same day, take your normal dose (one tablet) on the next day. Do not take a double dose to make up for a forgotten dose.

If you are unsure about what to do ask your doctor or pharmacist.

If you stop taking Moxifloxacin

If you stop taking this medicine too soon your infection may not be completely cured. Talk to your doctor if you wish to stop taking your tablets before the end of the course of treatment.

If you have any further questions about this medicine, ask your doctor or pharmacist.

  1. Possible Side Effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The most serious side effects observed during treatment with Moxifloxacin are listed below:

If you notice

  • an abnormal fast heart rhythm (rare side effect)
  • that you suddenly start feeling unwell or notice yellowing of the whites of the eyes, dark urine, itching of the skin, a tendency to bleed or disturbances of thought or wakefulness (these can be signs and symptoms of fulminant inflammation of the liver potentially leading to life-threating liver failure (very rare side effect, fatal cases have been observed))
  • alterations of the skin and mucous membranes like painful blisters in the mouth/nose or at the penis/vagina (Stevens-Johnson syndrome or toxic epidermal necrolysis) (very rare side effects, potentially life threatening)
  • inflammation of blood vessels (signs could be red spots on your skin, usually on your lower legs or effects like joint pain) (very rare side effect)
  • a severe, sudden generalised allergic reaction incl. very rarely a life-threatening shock (e.g. difficulty in breathing, drop of blood pressure, fast pulse) (rare side effect)
  • swelling incl. swelling of the airway (rare side effect, potentially life-threatening)
  • convulsions (rare side effect)
  • troubles associated with the nervous system such as pain, burning, tingling, numbness and/or weakness in extremities (rare side effect)
  • depression (in very rare cases leading to self-harm, such as suicidal ideations/thoughts, or suicide attempts) (rare side effect)
  • insanity (potentially leading to self-harm, such as suicidal ideations/thoughts, or suicide attempts) (very rare side effect)
  • severe diarrhoea containing blood and/or mucus (antibiotic associated colitis incl. pseudomembranous colitis), which in very rare circumstances, may develop into complications that are life-threatening (rare side effects)
  • pain and swelling of the tendons (tendonitis) (rare side effect) or a tendon rupture (very rare side effect)

stop taking Moxifloxacin and tell your doctor immediately as you may need urgent medical advice.

In addition, if you notice

  • transient loss of vision (very rare side effect),
  • discomfort or pain to the eyes, especially due to light exposure (very rare to rare side effect)

contact an eye specialist immediately.

If you have experienced life-threatening irregular heart beat (Torsade de Pointes) or stopping of heart beat while taking Moxifloxacin (very rare side effects), tell your treating doctor immediately that you have taken Moxifloxacin and do not restart the treatment.

A worsening of the symptoms of myasthenia gravis has been observed in very rare cases. If this happens, consult your doctor immediately.

If you suffer from diabetes and you notice that your blood sugar is increased or decreased (rare or very rare side effect), inform your doctor immediately.

If you are elderly with existing kidney problems and you notice decrease in urine output, swelling in your legs, ankles or feet, fatigue, nausea, drowsiness, shortness of breath or confusion (these can be signs and symptoms of kidney failure, a rare side effect), consult your doctor immediately.

Other side effects which have been observed during treatment with Moxifloxacin are listed below by how likely they are:

Common (may affect up to 1 in 10 people)

  • nausea
  • diarrhoea
  • dizziness
  • stomach and abdominal ache
  • vomiting
  • headache
  • increase of a special liver enzyme in the blood (transaminases)
  • infections caused by resistant bacteria or fungi e.g. oral and vaginal infections caused by Candida
  • change of the heart rhythm (ECG) in patients with low blood potassium level

Uncommon (may affect up to 1 in 100 people)

  • rash
  • stomach upset (indigestion/heartburn)
  • changes in taste (in very rare cases loss of taste)
  • sleep problems (predominantly sleeplessness)
  • increase of a special liver enzyme in the blood (gamma-glutamyl-transferase and/or alkaline phosphatase)
  • low number of special white blood cells (leukocytes, neutrophils)
  • constipation
  • itching
  • sensation of dizziness (spinning or falling over)
  • sleepiness
  • wind
  • change of the heart rhythm (ECG)
  • impaired liver function (incl. increase of a special liver enzyme in the blood (LDH))
  • decreased appetite and food intake
  • low white blood cells count
  • aches and pains such as back, chest, pelvic and extremities pains
  • increase of special blood cells necessary for blood clotting
  • sweating
  • increased specialised white blood cells (eosinophils)
  • anxiety
  • feeling unwell (predominantly weakness or tiredness)
  • shaking
  • joint pain
  • palpitations
  • irregular and fast heart beat
  • difficulty in breathing incl. asthmatic conditions
  • increase of a special digestive enzyme in the blood (amylase)
  • restlessness / agitation
  • tingling sensation (pins and needles) and/or numbness
  • skin hives
  • widening of blood vessels
  • confusion and disorientation
  • decrease of special blood cells necessary for blood clotting
  • visual disturbances incl. double and blurred vision
  • decreased blood clotting
  • increased blood lipids (fats)
  • low red blood cell count
  • muscle pain
  • allergic reaction
  • increase of bilirubin in the blood
  • inflammation of the stomach
  • dehydration
  • severe heart rhythm abnormalities
  • dry skin
  • angina pectoris

Rare (may affect up to 1 in 1,000 people)

  • muscle twitching
  • muscle cramp
  • hallucination
  • high blood pressure
  • swelling (of the hands, feet, ankles, lips, mouth, throat)
  • low blood pressure
  • kidney impairment (incl. increase in special kidney laboratory test results like urea and creatinine)
  • inflammation of the liver
  • inflammation of the mouth
  • ringing/noise in the ears
  • jaundice (yellowing of the whites of the eyes or skin)
  • impairment of skin sensation
  • abnormal dreams
  • disturbed concentration
  • difficulty in swallowing
  • changes in smell (incl. loss of smell)
  • balance disorder and poor co-ordination (due to dizziness)
  • partial or total loss of memory
  • hearing impairment including deafness (usually reversible)
  • increased blood uric acid
  • emotional instability
  • impaired speech
  • fainting
  • muscle weakness

Very rare (may affect up to 1 in 10,000 people)

  • inflammation of joints
  • abnormal heart rhythms
  • increase of skin sensitivity
  • a feeling of self-detachment (not being yourself)
  • increased blood clotting
  • muscle rigidity
  • significant decrease of special white blood cells (agranulocytosis)

Very rare cases of long lasting (up to months or years) or permanent adverse drug reactions, such as tendon inflammations, tendon rupture, joint pain, pain in the limbs, difficulty in walking, abnormal sensations such as pins and needles, tingling, tickling, burning, numbness or pain (neuropathy), depression, fatigue, sleep disorders, memory impairment, as well as impairment of hearing, vision, and taste and smell have been associated with administration of quinolone and fluoroquinolone antibiotics, in some cases irrespective of pre-existing risk factors.

Furthermore, there have been very rare cases of the following side effects reported following treatment with other quinolone antibiotics, which might possibly also occur during treatment with Moxifloxacin:

  • Raised pressure in the skull (symptoms include headache, visual problems including blurred vision, “blind” spots, double vision, loss of vision)
  • Increased blood sodium levels
  • Increased blood calcium levels
  • A special type of reduced red blood cell count (haemolytic anaemia)
  • Muscle reactions with muscle cell damage
  • Increased sensitivity of the skin to sunlight or UV light.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

  1. How to store Moxifloxacin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the blister and on the carton. The expiry date refers to the last day of that month.

Do not store above 25°C.

Store in the original package in order to protect from moisture.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. Contents of the pack and other information

What Moxifloxacin contains

The active substance is moxifloxacin.

Each film-coated tablet contains:
Moxifloxacin Hydrochloride USP
Equivalent to Moxifloxacin   400mg
Colours: Red Oxide of Iron & Titanium Dioxide

The other ingredients are:
Tablet core: Microcrystalline cellulose, Croscarmellose sodium, Lactose monohydrate and Magnesium stearate.
Film coating: Hypromellose, Macrogol, Ferric oxide and Titanium dioxide.

What Moxifloxacin looks like and contents of the pack

Each dull red film-coated tablet with an oblong, convex shape.

PVC/Aluminium Blister Pack 10, 20, 30, 40, 50, 60, 90, 100 and 200 Tablets.

Not all pack sizes may be marketed.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com