Consumer medicine information

Moxifloxacin APO

Moxifloxacin

BRAND INFORMATION

Brand name

Moxifloxacin APO

Active ingredient

Moxifloxacin

Schedule

SUMMARY CMI

MOXIFLOXACIN APO TABLETS

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I using MOXIFLOXACIN APO?

MOXIFLOXACIN APO contains the active ingredient moxifloxacin hydrochloride monohydrate. MOXIFLOXACIN APO is used to treat infections of the lungs, airways and sinuses in adults.

For more information, see Section 1. Why am I using MOXIFLOXACIN APO? in the full CMI.

2. What should I know before I use MOXIFLOXACIN APO?

Do not use if you have ever had an allergic reaction to moxifloxacin or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use MOXIFLOXACIN APO? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with MOXIFLOXACIN APO and affect how it works.

The main types of medicines that affect how MOXIFLOXACIN APO works include warfarin, medicines to treat abnormal heart rhythm, medicines which affect heart rhythm, antacids, multivitamins, mineral supplements and corticosteroids.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use MOXIFLOXACIN APO?

The usual adult dosage for MOXIFLOXACIN APO tablets for most infections is one 400 mg tablet once daily for 5 to 10 days.
Your doctor will determine the duration of time that you take the tablets depending on the type of infection you have

More instructions can be found in Section 4. How do I use MOXIFLOXACIN APO? in the full CMI.

5. What should I know while using MOXIFLOXACIN APO?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using MOXIFLOXACIN APO. Avoid exposure to ultraviolet radiation and sunlight Call your doctor immediately if you experience allergic reaction, diarrhoea, feel any discomfort, pain, swelling or inflammation of a tendon, palpitations, symptoms of depression or self-harming, develop pain, burning, tingling, numbness or weakness in any part of the body, or develop photosensitivity.
Things you should not do	Do not stop taking your tablets because you are feeling better unless your doctor told you so.
Driving or using machines	MOXIFLOXACIN APO tablets may cause dizziness or faintness in some people. Be careful when driving or operating machinery until you know how this medicine affects you.
Looking after your medicine	Keep your medicine in its original packaging until it is time to take it. Keep your medicine in a cool dry place where the temperature will stay below 30°C.

For more information, see Section 5. What should I know while using MOXIFLOXACIN APO? in the full CMI.

6. Are there any side effects?

Less serious side effects: redness or pain at the site of injection, headache, dizziness, nausea, vomiting, stomach pains, thrush in the mouth or vagina. Serious side effects: allergic reactions, palpitations, fainting, seizures, diarrhoea, tendon pain, swelling or rupture, pain, burning, tingling, numbness or weakness that starts or worsens on MOXIFLOXACIN APO, eyesight problems, changes in mood or thoughts, skin reactions, blistering or peeling, and symptoms of liver damage.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

BOXED WARNING:

Serious disabling and potentially irreversible adverse reactions

Fluoroquinolones, including moxifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions involving different body systems that have occurred together in the same patient. Patients of any age or without pre-existing risk factors have experienced these adverse reactions. These include but are not limited to serious adverse reactions involving the nervous system (Seizures, Peripheral neuropathy), musculoskeletal system (Tendonitis and tendon rupture) and psychiatric effects (Psychiatric reactions).

FULL CMI

MOXIFLOXACIN APO TABLETS

Active ingredient: moxifloxacin hydrochloride monohydrate

Consumer Medicine Information (CMI)

This leaflet provides important information about using MOXIFLOXACIN APO. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using MOXIFLOXACIN APO.

Where to find information in this leaflet:

1. Why am I using MOXIFLOXACIN APO?
2. What should I know before I use MOXIFLOXACIN APO?
3. What if I am taking other medicines?
4. How do I use MOXIFLOXACIN APO?
5. What should I know while using MOXIFLOXACIN APO?
6. Are there any side effects?
7. Product details

1. Why am I using MOXIFLOXACIN APO?

MOXIFLOXACIN APO contains the active ingredient moxifloxacin hydrochloride monohydrate.
MOXIFLOXACIN APO is an antibiotic belonging to a group of medicines called quinolones. These antibiotics work by killing the bacteria that are causing your infection.

Moxifloxacin will not work against infections caused by viruses such as colds or the flu.

MOXIFLOXACIN APO is used to treat infections of the lungs, airways and sinuses in adults. In certain infections, you may require treatment with moxifloxacin injection followed by a course of moxifloxacin tablets e.g. severe and complicated skin and skin structure infections.

2. What should I know before I use MOXIFLOXACIN APO?

Warnings

Do not use MOXIFLOXACIN APO if:

You are allergic to moxifloxacin, other medicines belonging to the quinolone family (e.g. ciprofloxacin, norfloxacin or nalidixic acid) or any of the ingredients listed at the end of this leaflet.
Have or have had any of the following medical conditions:
- a condition called "QTc prolongation", which is a type of abnormal heart rhythm
- blood tests that show lower than normal potassium levels
Do not take this medicine if you are taking medicines to treat arrhythmia – fast, slow or irregular heart beat (e.g. quinidine, procainamide, amiodarone or sotalol).
Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

have any other medical conditions
take any medicines for any other condition
you or someone in your family has a history of heart rhythm problems
are taking any medicine that might affect heart rhythm (e.g. quinidine, procainamide, amiodarone, sotalol, erythromycin, tricyclic antidepressants, antipsychotics)
have low potassium levels
have had any condition affecting the brain, particularly if you have ever had a seizure (‘fit’)
have severe liver problems
have a condition called myasthenia gravis (a diseasecausing muscle weakness)
have or had a mental illness
have diabetes

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Moxifloxacin is not recommended if you are pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Moxifloxacin passes into breast milk and may affect your baby.

Children under 18 years old

MOXIFLOXACIN APO should not be used in children under 18 years of age.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with MOXIFLOXACIN APO tablets and affect how it works.

MOXIFLOXACIN APO may have an effect on the heart rhythm. If you are using other medicines that affect the heart at the same time as MOXIFLOXACIN APO there is an increased risk of altering your heart rhythm.

Tell your doctor if you are taking:

warfarin, used to stop blood clots – your doctor should perform INR testing and may adjust your warfarin dose
medicines used to treat abnormal heart rhythm (e.g. quinidine, procainamide, amiodarone or sotalol)
medicines that can affect the heart rhythm (erythromycin, tricyclic antidepressants or antipsychotics)
corticosteroids.

These medicines and MOXIFLOXACIN APO may affect each other or increase the chance of you getting a side effect

Some medicines may interfere with the absorption of MOXIFLOXACIN APO tablets. These medicines include:

antacids, multivitamins, mineral supplements and other medicines containing iron, zinc, magnesium, aluminium or calcium
sucralfate, used to treat duodenal or stomach ulcers
didanosine, used to treat viral infections.

You can still take these medicines while you are taking moxifloxacin.

However, you must take moxifloxacin at least 2 hours before, or 4 hours after taking any of these medicines to make sure there is no problem with absorption.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect MOXIFLOXACIN APO.

4. How do I use MOXIFLOXACIN APO?

How much to take

The usual adult dosage for MOXIFLOXACIN APO tablets for most infections is one 400 mg tablet once daily for 5 to 10 days.
Some types of infections may require longer treatment. Your doctor will determine the duration of time that you take the tablets depending on the type of infection you have. It is important that you take the full course of treatment your doctor has prescribed to you
You should not exceed the dose your doctor has prescribed for you. The risk of heart rhythm problems may increase with an increase of the dose.

When to take MOXIFLOXACIN APO

Moxifloxacin tablets are usually taken once a day.
Take your medicine at about the same time each day.
It can be taken with or without food. It is advisable to drink fluids liberally
Swallow the tablet whole with water. Do not chew the tablet.
Do not take moxifloxacin at the same time as taking antacids (containing magnesium, calcium or aluminium), multivitamins (containing iron or zinc), sucralfate (a medicine to treat stomach ulcers) or didanosine (a medicine to treat viral infections).
Taking these medicines at the same time as moxifloxacin can interfere with the absorption of moxifloxacin tablets and reduce their effectiveness in fighting the infection.
You must take moxifloxacin at least 2 hours before, or 4 hours after taking any of these medicines.

If you forget to use MOXIFLOXACIN APO

MOXIFLOXACIN APO should be used regularly at the same time each day.

If you forget to take your tablet and it is:

8 hours or more until your next scheduled dose, take your missed dose right away. Then take the next dose at your regular time.
Less than 8 hours until your next scheduled dose, do not take the missed dose. Take the next dose at your regular time.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you use too much MOXIFLOXACIN APO

If you think that you have used too much MOXIFLOXACIN APO, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using MOXIFLOXACIN APO?

Things you should do

Tell all doctors, dentists and pharmacists who are treating you that you are taking MOXIFLOXACIN APO.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking MOXIFLOXACIN APO tablets.

Avoid prolonged exposure to ultraviolet radiation and sunlight. MOXIFLOXACIN APO can make your skin more susceptible to sunburn. Protect your skin when you are in the sun, especially between 10am and 3pm. If you are outdoors, wear protective clothing and use a SPF 30+ sunscreen.

Call your doctor straight away if you:

become pregnant while you are taking MOXIFLOXACIN APO
develop an allergic reaction (e.g. skin rash) while taking AVELOX, even following a single dose. Stop taking it and tell your doctor.
develop diarrhoea. Tell your doctor even if it occurs several weeks after you have stopped taking MOXIFLOXACIN APO.
feel any discomfort, pain, swelling or inflammation of a tendon.
experience palpitations (fast or irregular heart beats) or fainting spells during treatment
experience symptoms of depression or self-harming behaviour. MOXIFLOXACIN APO should be discontinued.
develop pain, burning, tingling, numbness or weakness in any part of the body. MOXIFLOXACIN APO should be discontinued immediately.
develop photosensitivity (getting sunburnt very easily)

Remind any doctor, dentist or pharmacist you visit that you are using MOXIFLOXACIN APO.

Things you should not do

Do not give your MOXIFLOXACIN APO tablets to anyone else, even if they have the same condition as you.
Do not use MOXIFLOXACIN APO to treat other conditions unless your doctor tells you to.
Do not change the dose.
Do not stop using this medicine suddenly or lower the dosage without checking with your doctor first, especially if you are feeling better.
If you do not complete the full course prescribed by your doctor, some of the bacteria causing your infection may not be killed. These bacteria may continue to grow and multiply so that your infection may not clear up completely or it may return.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how MOXIFLOXACIN APO affects you.

MOXIFLOXACIN APO tablets may cause dizziness or faintness in some patients. The ability to drive and/or operate machinery may be impaired.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

Keep your medicine in its original packaging until it is time to take it.
If you take your medicine out of its original packaging it may not keep well.
Keep your medicine in a cool dry place where the temperature will stay below 30°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

in the bathroom or near a sink, or
in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking this medicine.

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects

What to do

Nervous system-related:

headache
dizziness or light-headedness

Gastrointestinal system-related:

nausea, vomiting
stomach pains, diarrhoea

Fungal infection:

thrush in the mouth (sore creamyyellow raised patches in mouth) or in the vagina (itching, burning or thick white discharge)

Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects

What to do

Immune-related:

allergic reactions such as skin rashes, swelling of the face, lips, mouth or throat

Nervous system-related:

palpitations or fainting spells
fits (seizures, convulsions)
Gastrointestinal system-related:
watery or bloody diarrhoea, even if it occurs several weeks after finishing your tablets It may be a sign that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take any medications for diarrhoea without checking with your doctor.

Muscle-related:

pain, swelling or rupture of a tendon
pain, burning, tingling, numbness or weakness that starts or worsens on MOXIFLOXACIN APO

Eye-related:

visual disturbances (eyesight problems)

Mood-related:

changes in your mood or thoughts that worry you

Liver damage: suddenly feeling unwell or sick and develop symptoms such as:

yellowing of the skin and in the whites of your eyes, also called jaundice
pain in liver area
dark urine
itchy skin
tendency to bleed

Skin-related:

skin reaction or blistering and/or peeling of the skin and/or mucosal reactions

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What MOXIFLOXACIN APO contains

Active ingredient (main ingredient)	Moxifloxacin hydrochloride monohydrate
Other ingredients (inactive ingredients)	Lactose (223.7mg/tablet) Povidone Croscarmellose sodium Colloidal anhydrous silica Magnesium stearate Titanium dioxide Hypromellose Macrogol 400 Iron oxide red
Potential allergens	This medicine contains sugars as lactose.

Do not take this medicine if you are allergic to any of these ingredients.

What MOXIFLOXACIN APO looks like

MOXIFLOXACIN APO is dull red coloured, caplet shaped, film coated tablets, debossed with M on one side and 400 on other side. (Aust R 309824).

Who distributes MOXIFLOXACIN APO

Arrotex Pharmaceuticals Pty Ltd
15 - 17 Chapel Street
Cremorne, Victoria 3121
Australia

This leaflet was prepared in October 2024.

Published by MIMS December 2024

BRAND INFORMATION

Brand name

Moxifloxacin APO

Active ingredient

Moxifloxacin

Schedule

1 Name of Medicine

Moxifloxacin hydrochloride monohydrate.

2 Qualitative and Quantitative Composition

Each film coated tablet contains 400 mg moxifloxacin (as hydrochloride monohydrate).

Excipients with known effects.

Lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Dull red coloured, caplet shaped, film coated tablets, debossed with "M" on one side and "400" on other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Moxifloxacin is indicated for the treatment of adults with infections caused by susceptible organisms in the conditions: acute bacterial sinusitis; community acquired pneumonia; acute exacerbations of chronic bronchitis.
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 moxifloxacin may be initiated, in some conditions, before results of these tests are known. Once results become available, therapy should be continued with the most appropriate antibiotic therapy.
Consideration should be given to available official guidance on the appropriate use of antibacterial agents.

4.2 Dose and Method of Administration

This medicine is available as a 400 mg film coated tablet for oral administration.
Moxifloxacin injection is unavailable in this brand however is available in other brands. Where correct dosing requires moxifloxacin injection formulation, refer to the specific product information for this formulation for their complete dosage and administration instructions.

Dosage.

The usual dose of moxifloxacin is 400 mg orally or intravenously every 24 hours. The recommended dose should not be exceeded. The duration of therapy depends on the type of infection as described in Table 1.

The recommended duration of therapy for the treatment indication should not be exceeded.
Oral doses should be administered at least two hours before or four hours after antacids containing magnesium or aluminium, products containing iron, or multivitamins containing zinc. The film-coated tablet should be swallowed whole with sufficient liquid and may be taken independent of meals.
When switching from intravenous to oral dosage administration, no dosage adjustment is necessary. Patients whose therapy is started with moxifloxacin IV may be switched to moxifloxacin tablets when clinically indicated at the discretion of the physician.

Dose adjustments.

Elderly.

No adjustment of dose is necessary.

Paediatric.

The use of moxifloxacin in children is not recommended (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

Interethnic differences.

No adjustment of dosage is required in different ethnic groups.

Hepatic impairment.

No dosage adjustment is required in patients with impaired liver function. As limited clinical data are available in severe hepatic impairment (Child-Pugh C), the use of moxifloxacin in this patient group is not recommended (also see Section 4.4 Special Warnings and Precautions for Use for use in Child-Pugh C patients).

Renal impairment.

No dosage adjustment is required in renally impaired patients (including patients whose creatinine clearance ≤ 30 mL/min/1.73 m²) and in patients on chronic dialysis i.e. haemodialysis and continuous ambulatory peritoneal dialysis.

4.3 Contraindications

Known hypersensitivity to moxifloxacin, any other quinolones or to any of the excipients in this medicine.
Because of an effect of moxifloxacin on the QTc interval of the electrocardiogram and a lack of clinical experience with the drug in the following patient populations, the drug is contraindicated in patients with known prolongation of the QTc interval, patients with uncorrected hypokalaemia and patients receiving Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic agents (see Section 4.4 Special Warnings and Precautions for Use).
Also see Section 4.2 Dose and Method of Administration, Paediatric; Section 4.4 Special Warnings and Precautions for Use, General and Paediatric use.

4.4 Special Warnings and Precautions for Use

Moxifloxacin injection is unavailable in this brand, however this dosage form is available in other brands. Special warnings and precautions for use, pharmacokinetic and pharmacodynamic information obtained using moxifloxacin injection formulation is also included in the following sections for prescriber information.
Fluoroquinolones, including moxifloxacin, have been associated with disabling and potentially persistent adverse reactions involving different body systems that have occurred together in the same patient. Patients of any age or without pre-existing risk factors have experienced these adverse reactions. These include, but are not limited to, serious adverse reactions involving the nervous system (see Section 4.4 Special Warnings and Precautions for Use, Seizures and Peripheral neuropathy) and musculoskeletal system (see Section 4.4 Special Warnings and Precautions for Use, Tendonitis and tendon rupture) and psychiatric effects (see Section 4.4 Special Warnings and Precautions for Use, Psychiatric reactions).

General.

The safety and effectiveness of moxifloxacin in paediatric patients, adolescents (less than 18 years of age), pregnant women and lactating women have not been established. See Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy and Use in lactation; Section 4.4 Special Warnings and Precautions for Use, Paediatric use.

Cardiac effects.

At high concentrations, moxifloxacin is an inhibitor of the delayed rectifier potassium current of the heart. Moxifloxacin has been shown to prolong the QTc interval in some patients. The magnitude of this effect may increase with increasing concentrations of the drug, therefore, the recommended dose or infusion rate (400 mg within 60 minutes) should not be exceeded. QTc prolongation may lead to an increased risk for ventricular arrhythmias (including torsade de pointes) and cardiac arrest.
In 787 patients receiving oral treatment with paired valid ECGs in Phase III clinical trials, the mean ± SD effect of moxifloxacin 400 mg on the QTc interval was small (6 ± 26 ms). 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.
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 9 ms (± 24) on Day 1 (n = 69) and 3 ms (± 29) on Day 3 (n = 290). In sequential IV/oral trials in community acquired pneumonia, QT interval prolongation was reported in 1.3% (6/550) in the moxifloxacin group and 0.7% (4/579) in the comparator group. No cases of ventricular arrhythmia associated with QT interval prolongation was observed in these studies.
No cardiovascular morbidity or mortality was attributed to moxifloxacin among over 5000 patients treated with oral moxifloxacin including 223 patients who were hypokalaemic at the start of treatment.
Due to limited clinical experience, patients with uncorrected electrolyte disorders particularly hypokalaemia, known prolongation of the QTc interval, or those concurrently receiving drugs that prolong the QTc interval, in particular Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmics, should not receive moxifloxacin. An additive effect of moxifloxacin and drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants cannot be excluded, therefore moxifloxacin should be used with caution when given concurrently with these drugs. The effect of moxifloxacin on patients with congenital prolongation of the QTc interval has not been studied, however, it is expected that these individuals may be more susceptible to drug induced QTc prolongation.
Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients), such as clinically significant bradycardia and acute myocardial ischaemia.

Antibiotic-associated colitis.

Pseudomembranous colitis has been reported with virtually all broad spectrum antibiotics including moxifloxacin. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with moxifloxacin use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate therapy such as oral antibacterial agents effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs inhibiting peristalsis are contraindicated in patients who develop serious diarrhoea.

Tendonitis and tendon rupture.

Tendonitis and tendon rupture (predominantly Achilles tendon), sometimes bilateral, that required surgical repair or resulted in prolonged disability have been reported with quinolone therapy including moxifloxacin. This may occur even within the first 48 hours of treatment, and cases occurring up to several months after completion of therapy have been reported. The risk of tendinopathy may be increased in elderly patients, during strenuous physical activity, in patients treated concomitantly with corticosteroids, in patients with renal impairment and in patients with solid organ transplants. At the first sign of tendonitis (e.g. painful swelling, inflammation) the affected extremity should be kept at rest, any inappropriate physical exercise should be avoided, a physician should be consulted and moxifloxacin should be discontinued.

Seizures.

Seizures may occur with fluoroquinolone therapy. Moxifloxacin should be used with caution in patients with known or suspected CNS disorders (e.g. lowered convulsion threshold, previous history of convulsion, reduced cerebral blood flow, altered brain structure or stroke), that may predispose them to seizures or lower the seizure threshold.

Myasthenia gravis.

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

Peripheral neuropathy.

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoaesthesias, dysaesthesias or weakness have been reported in patients receiving quinolones including moxifloxacin. Moxifloxacin should be discontinued in patients experiencing symptoms of neuropathy, including pain, burning, tingling, numbness and/or weakness, in order to prevent the development of an irreversible condition (see Section 4.8 Adverse Effects (Undesirable Effects)).

Psychiatric reactions.

Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of psychiatric adverse reactions including: toxic psychosis, psychotic reactions progressing to suicidal ideations/thoughts, hallucinations or paranoia; depression, or self-injurious behaviour such as attempted or completed suicide; anxiety, agitation, or nervousness; confusion, delirium, disorientation, or disturbances in attention; insomnia or nightmares; memory impairment. These reactions may occur following the first dose. Advise patients receiving moxifloxacin to inform their healthcare provider immediately if these reactions occur, discontinue the drug and institute appropriate care.

Vision disorders.

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately (see Section 4.8 Adverse Effects (Undesirable Effects)).

Photosensitivity potential.

Phototoxicity has been reported with other quinolones. However, in specially designed preclinical and clinical studies photosensitivity has not been observed with moxifloxacin. In addition, since first marketed there has been no clinical evidence that moxifloxacin causes photosensitivity reactions. Nevertheless, patients should be advised to avoid extensive exposure to either UV irradiation or sunlight.

Hypersensitivity reactions.

Hypersensitivity and allergic reactions have been reported following the first dose. In very rare instances these can progress to life-threatening shock. Moxifloxacin should be discontinued and appropriate therapy commenced in these cases. Anaphylactic reactions in very rare instances can progress to a life-threatening shock, in some instances after the first administration. In these cases, the treatment with moxifloxacin has to be discontinued, medical treatment (e.g. treatment for shock) is required.

Skin reactions.

Cases of bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with moxifloxacin (see Section 4.8 Adverse Effects (Undesirable Effects), Post-marketing adverse event reports). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.

Osteomyelitis.

In patients with complicated skin and skin structure infection who have associated osteomyelitis there are no data demonstrating the efficacy and safety of treatment with moxifloxacin.

Dysglycaemia.

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

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.

Other.

Moxifloxacin is not recommended for the treatment of methicillin resistant Staphylococcus aureus (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 Pharmacodynamic Properties, Mechanism of action).
Moxifloxacin in vitro activity may interfere with the Mycobacterium spp. culture test by suppression of mycobacterial growth, causing false negative results in specimens from patients currently taking moxifloxacin.

Paediatric use.

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 weight bearing joints and other signs of arthropathy in immature animals of various species. Therefore, moxifloxacin should not be used in paediatric patients.

Use in the elderly.

No data available.

Patients with severe hepatic impairment.

As limited clinical data are available in severe hepatic impairment (Child-Pugh C), the use of moxifloxacin in this patient group is not recommended. Cases of fulminant hepatitis potentially leading to life threatening liver failure (including fatal cases) have been reported with moxifloxacin (see Section 4.8 Adverse Effects (Undesirable Effects), Post-marketing adverse event reports). Patients should be advised to contact their doctor prior to continuing treatment if signs and symptoms of 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.

Information for patients.

To assure safe and effective use of moxifloxacin, the following information and instruction should be communicated to the patient when appropriate.
Patients should be advised:
that moxifloxacin may produce an effect on the electrocardiogram and may add to the effect of other drugs on the electrocardiogram. Consequently, patients should advise their physician of any other medications that they are currently taking, including over-the-counter medications;
that the recommended dose should not be exceeded;
to inform their physician of any personal or family history of QT prolongation;
to contact their physician if they experience palpitations or fainting spells while taking moxifloxacin;
that moxifloxacin tablets may be taken with or without meals, and to drink fluids liberally;
that moxifloxacin tablets should be taken at least 2 hours before or 4 hours after multivitamins (containing iron or zinc), antacids (containing magnesium, calcium, or aluminium), sucralfate, or didanosine chewable/buffered tablets or the paediatric powder for oral solution (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions);
that moxifloxacin may be associated with hypersensitivity reactions, even following a single dose, and to discontinue the drug at the first sign of a skin rash or other signs of an allergic reaction;
to discontinue treatment, rest and refrain from exercise, and inform their physician if they experience pain, inflammation or rupture of a tendon;
that moxifloxacin may cause dizziness and light-headedness, therefore, patients should know how they react to this drug before they operate an automobile or machinery or engage in activities requiring mental alertness or co-ordination;
that convulsions have been reported in patients receiving quinolones, and they should notify their physician before taking this drug if there is any history of this condition.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Drugs which can affect moxifloxacin.

See Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use for drugs known to prolong the QT interval.

Antacids, minerals and multi-vitamins.

Concomitant ingestion of moxifloxacin together with antacids, minerals and multi-vitamins may result in impaired absorption of the drug due to the formation of chelate complexes with the multivalent cations contained in these preparations. This may lead to lower than desired plasma concentrations. Hence, oral doses of moxifloxacin should be administered at least 2 hours before or four hours after ingestion of antacids, and other preparations containing magnesium, aluminium, sucralfate and other minerals such as iron or zinc.

Anti-retroviral drugs.

Oral doses of moxifloxacin should be administered at least 2 hours before or after ingestion of antacid buffered anti-retroviral drugs (e.g. didanosine).

Drugs shown not to affect moxifloxacin.

For the following substances absence of a clinically relevant interaction with moxifloxacin was proven: atenolol, ranitidine, calcium supplements, theophylline, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid. No dose adjustment is necessary for these drugs.

Ranitidine.

The concomitant administration with ranitidine did not change the absorption characteristics of moxifloxacin significantly. Absorption parameters (C_max, t_max, AUC) were very similar indicating an absence of influence of gastric pH on moxifloxacin uptake from the gastrointestinal tract.

Calcium supplements.

When given with high dose calcium supplements only a slightly reduced rate of absorption was observed while extent of absorption remained unaffected. The effect of high dose calcium supplements on the absorption of moxifloxacin is considered as clinically not relevant.

Warfarin.

No interaction during concomitant treatment with warfarin on prothrombin time and other coagulation parameters has been observed.
Changes in INR (International Normalized Ratio): cases of increased anticoagulant activity have been reported in patients receiving oral anticoagulants concurrently with antibiotics, including moxifloxacin. The infectious disease (and its accompanying inflammatory process), age and general status of the patient are risk factors. Although an interaction between moxifloxacin and warfarin was not demonstrated in clinical trials, INR monitoring should be performed, and if necessary, the oral anticoagulant dosage should be adjusted as appropriate.

Oral contraceptives.

No interaction has occurred following concomitant oral administration of moxifloxacin with oral contraceptives.

Itraconazole.

Exposure (AUC) to itraconazole was only marginally altered under concomitant moxifloxacin treatment. Pharmacokinetics of moxifloxacin were not significantly altered by itraconazole. No dose adjustment is necessary for itraconazole when given with moxifloxacin and vice versa.

Digoxin.

The pharmacokinetics of digoxin are not significantly influenced by moxifloxacin (and vice versa). After repeated dosing in healthy volunteers, moxifloxacin increased C_max of digoxin by approximately 30% at steady state without affecting AUC or trough levels.

Morphine.

Parenteral administration of morphine with moxifloxacin did not reduce the oral bioavailability of moxifloxacin and only slightly decreased C_max (17%).

Atenolol.

The pharmacokinetics of atenolol are not significantly altered by moxifloxacin. Following single dose administration in healthy subjects, AUC was marginally increased (by approximately 4%) and peak concentrations were decreased by 10%.

Theophylline.

No influence of moxifloxacin on theophylline pharmacokinetics (and vice versa) at steady state was detected, indicating that moxifloxacin does not interfere with the 1A2 subtypes of the cytochrome P450 enzymes; theophylline concentrations were not elevated at steady state during combined treatment with moxifloxacin (C_max 10.5 vs 10.1 mg/L without vs with theophylline).

Probenecid.

No significant effect on apparent total body clearance and renal clearance of moxifloxacin was found in a clinical study investigating the impact of probenecid on renal excretion. Therefore, dosing adjustments need not be made when both drugs are administered concurrently.

Antidiabetic agents.

No clinically relevant interaction was seen between glibenclamide and moxifloxacin.

Use of countermeasures.

Concomitant dosing of charcoal and 400 mg oral moxifloxacin reduced the systemic availability of the drug by more than 80% by preventing absorption in vivo. The application of activated charcoal in the early absorption phase prevents further increase of systemic exposure in cases of overdose.

Drug-drug interactions.

The potential for pharmacokinetic drug interactions between moxifloxacin and theophylline, warfarin, digoxin, probenecid, ranitidine, glyburide, iron, and antacids has been evaluated. No clinically significant drug-drug interactions were found with theophylline, warfarin, digoxin, probenecid, ranitidine or glibenclamide, but, as with all other quinolones, iron and antacids significantly reduced the bioavailability of orally administered moxifloxacin (see Section 4.4 Special Warnings and Precautions for Use).
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 electro-cardiogram. In clinical trials, over 200 moxifloxacin-treated patients receiving drugs that prolong the QTc interval, 44 had electrocardiograms before and during moxifloxacin treatment. These patients demonstrated less of a change in QTc on moxifloxacin (1 ± 35 ms) than patients not receiving drugs that prolong the QTc interval (7 ± 25 ms). However, sotalol, a Class III antiarrhythmic, has been shown to further increase the QTc interval when combined with intravenous (IV) moxifloxacin in dogs. Therefore, moxifloxacin should not be used with Class IA or Class III antiarrhythmics (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Oral treatment of male rats with a dose of 500 mg/kg/day moxifloxacin (about 2.5 times clinical exposure, based on AUC) or an intravenous dose of 45 mg/kg/day (about 0.5 times clinical exposure, based on the estimated AUC) had no effect on fertility. At the oral dose of 500 mg/kg/day there were slight effects on sperm morphology (head-tail separations) in male rats. Female rat fertility was unaffected by the same oral moxifloxacin dose, which resulted in a low relative systemic drug exposure (0.4 times clinical exposure), and slightly reduced oestrus cycling. Female rat fertility was also unaffected by an IV dose of 45 mg/kg/day (about 0.3 times clinical exposure, based on the estimated AUC).
(Category B3)
Reproductive studies performed in rats, rabbits and monkeys indicate that placental transfer of moxifloxacin occurs. Moxifloxacin was not teratogenic in Cynomolgus monkeys administered oral doses of 100 mg/kg/day moxifloxacin (approximately 2 times clinical exposure at the maximum recommended dose based on AUC). Doses of 30 mg/kg/day and above (about 0.6 times clinical exposure in terms of the AUC) resulted in embryonic deaths and abortions. An increased incidence of smaller foetuses was observed at doses of 100 mg/kg/day. Teratogenicity was not seen in a study in rats, but the highest oral dose used (500 mg/kg/day) resulted in a lower (0.25 times) plasma drug exposure than would have been expected during therapy. The same oral dose given to rats from early gestation through to weaning was maternotoxic and was associated with reduced pup weights and increased perinatal mortality. Intravenous administration of 80 mg/kg/day to pregnant rats resulted in maternal toxicity and a marginal effect on fetal and placental weights and the appearance of the placenta. There was no evidence of teratogenicity at intravenous doses as high as 80 mg/kg/day (at least 0.2x clinical exposure, based on AUC). Intravenous administration of 20 mg/kg/day moxifloxacin (approximately equal to clinical exposure in terms of the AUC) to rabbits resulted in decreased fetal body weights, delayed fetal skeletal ossification, an increased incidence of fetuses and litters with malformations and an increased incidence of fetuses with prominent liver lobulation. Maternal toxicity in rabbits at 20 mg/kg/day intravenously included mortality, abortions, reduction of food consumption, decreased water intake, body weight loss and hypoactivity.
There are no adequate or well-controlled studies in pregnant women and because of the above findings in animal teratology studies, moxifloxacin therapy during pregnancy is not recommended.
Preclinical evidence indicates that small amounts of moxifloxacin may be secreted in human milk. Because of the potential for serious adverse reactions in infants nursing from mothers taking moxifloxacin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

4.7 Effects on Ability to Drive and Use Machines

Moxifloxacin may cause dizziness and light-headedness; therefore, patients should know how they react to this drug before they operate an automobile or machinery, or engage in activities requiring mental alertness or co-ordination.
Fluoroquinolones including moxifloxacin may result in an impairment of the patient's ability to drive or operate machinery due to CNS reactions and vision disorders (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Adverse drug reactions (ADRs) based on all clinical studies with moxifloxacin 400 mg (oral and sequential therapy) sorted by CIOMS III categories of frequency (overall n = 12,984, including n = 2,535 for sequential therapy studies; status: December 2005) are listed in Table 2.
ADRs listed under "common" were observed with a frequency below 3% with the exception of nausea and diarrhoea.
Within each frequency grouping, the ADRs are presented in order of decreasing seriousness. Frequencies are defined as: common ≥ 1/100 to < 1/10, uncommon ≥ 1/1000 to < 1/100, rare ≥ 1/10,000 to < 1/1000, very rare < 1/10,000.
In isolated instances, some serious adverse drug reactions may be long-lasting (> 30 days) and disabling; such as tendonitis, tendon rupture, musculoskeletal disorders, and other reactions affecting the nervous system including psychiatric disorders and disturbance of senses.
The following undesirable effects have a higher frequency in the subgroup of IV/oral sequentially treated patients:
Common: increased gamma-glutamyl-transferase.
Uncommon: hallucination, seizures of various clinical manifestations (incl. grand mal convulsions), hypotension, oedema, antibiotic-associated colitis (in very rare cases associated with life threatening complications), ventricular tachyarrhythmias, renal impairment and renal failure (due to dehydration esp. in elderly with pre-existing renal disorders).

Post-marketing adverse event reports.

Cardiovascular system disorders.

Very rare (< 0.01%): cardiac arrest and torsade de pointes, and usually in patients with concurrent severe underlying proarrhythmic conditions such as clinically significant bradycardia, acute myocardial ischaemia.

Hepatobiliary disorder.

Very rare (< 0.01%): fulminant hepatitis potentially leading to life-threatening liver failure (including fatal cases).

Musculoskeletal, connective tissue and bone disorder.

Very rare (< 0.01%): tendon rupture, gait disturbance (caused by muscular, tendon or joint symptoms), exacerbation of symptoms of myasthenia gravis.

Psychiatric disorders.

Very rare (< 0.01%): depression and/or psychotic reactions potentially culminating in self-injurious behaviour such as suicidal ideational thoughts or suicide attempts.

Nervous system disorders.

Very rare (< 0.01%): disturbed coordination leading to fall with injuries (esp. in elderly).

Skin and subcutaneous tissue disorders.

Very rare (< 0.01%): bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life threatening).

Renal and urinary disorders.

Uncommon (≥ 0.1% to < 1%): dehydration (caused by diarrhoea or reduced fluid intake).

Metabolism and nutrition disorders.

Hypoglycaemia.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems and contact Apotex Medical Information Enquiries/ Adverse Drug Reaction Reporting on 1800 195 055.

4.9 Overdose

Only limited data on overdose are available. Single oral doses of up to 2.8 g and multiple doses of 600 mg over 10 days were administered to healthy subjects without any significant undesirable effects. In the event of overdosage it is recommended that appropriate supportive care should be instituted as dictated by the patient's clinical status. The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase in systemic moxifloxacin exposure. Due to the potential for moxifloxacin to cause QT prolongation, patients should be carefully monitored following an overdose.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Moxifloxacin is an 8-methoxyfluoroquinolone antibiotic with a broad spectrum of activity and bactericidal action. The bactericidal action results from the inhibition of topoisomerase II or DNA gyrase and topoisomerase IV required for bacterial DNA replication, transcription, repair and recombination.
Moxifloxacin exhibits concentration dependent bactericidal killing. Minimum bactericidal concentrations are generally similar to minimum inhibitory concentrations. 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. There is no known cross-resistance between moxifloxacin and other classes of antibiotics. Although cross-resistance has been observed between moxifloxacin and other fluoroquinolones against gram-negative bacteria, gram-positive bacteria resistant to other fluoroquinolones may be susceptible to moxifloxacin.
Moxifloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in Section 4.1 Therapeutic Indications. See Table 3.

Moxifloxacin exhibits in vitro activity (MIC₉₀ ≤ 2 microgram/mL) against the following microorganisms, but their clinical significance is unknown. See Table 4.

Moxifloxacin does not reliably show activity against Pseudomonas aeruginosa.

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 and efflux mechanisms may, however, also affect the sensitivity of corresponding bacteria to moxifloxacin. Plasmid-mediated resistance has not been observed to date.
Cross resistance among quinolones has been observed. As moxifloxacin inhibits both topoisomerases II and IV, some gram-positive bacteria and anaerobes that are resistant to other quinolones are susceptible to moxifloxacin.
The frequency of acquired resistance may vary geographically and with time for certain species. Local area information on resistance of organisms is desirable, particularly when treating severe infections.

Effect on the intestinal flora in humans.

In two volunteer studies, the following changes in intestinal flora were seen following dosing with moxifloxacin. E. coli, Bacillus spp., Bacteroides vulgatus, Enterococci and Klebsiella spp. were reduced, as were the anaerobes Bifidobacterium, Eubacterium and Peptostreptococcus. These changes returned to normal within two weeks. Clostridium difficile toxin was not found.

Susceptibility tests.

Dilution or diffusion techniques - either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS).
Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of "susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Clinical trials.

In this section, overall clinical response is defined as the combined response rate at the end of treatment and follow-up visits (with failures at the end of treatment carried forward) in the per-protocol population. Bacteriological eradication is defined as eradication plus presumed eradication in microbiologically valid patients.
Acute bacterial exacerbation of chronic bronchitis. Moxifloxacin tablets (400 mg once daily for 5 days) were evaluated for acute bacterial exacerbation of chronic bronchitis in two large randomised, double-blind, controlled clinical studies. Clarithromycin (500 mg twice daily) was used as the active control in both studies and the treatment duration was 7 days in one study (0124), and 10 days in the other (0127). The overall clinical response and bacteriological eradication rates for the most frequently isolated pathogens are shown in Table 5.

Community acquired pneumonia. Three large randomised, double-blind controlled clinical studies were conducted to evaluate the efficacy of moxifloxacin tablets (400 mg once daily for 10 days) in patients with clinically and radiologically documented community acquired pneumonia. Clarithromycin (500 mg twice daily for 10 days) was used as the active control in two studies (0119 and 0130) and high dose amoxycillin (1000 mg three times daily for 10 days) in the remaining one (0140). The results of these studies are shown in Table 6.

Sequential IV/oral therapy.

Two large, randomised, controlled trials were conducted to compare the efficacy of sequential IV/PO moxifloxacin 400 mg QD for 7-14 days in the treatment of patients with clinically and radiologically documented mild-moderate or severe community acquired pneumonia. A double-blind study enrolled 516 patients from the U.S. and Canada compared moxifloxacin to an IV/PO fluoroquinolone control. Another study enrolled 628 patients from Europe, Israel and South Africa, and compared moxifloxacin to sequential IV/PO amoxicillin/clavulanate (1.2 g IV q8h/625 mg PO q8h) with or without high-dose IV/PO clarithromycin (500 mg BID). The primary efficacy analysis was conducted in clinically evaluable patients at the test of cure visit (Day 7-30 post-therapy for NA Study and Day 5-7 post-therapy for Ex-NA Study). The clinical success rate for moxifloxacin therapy was equivalent to the fluoroquinolone comparators (86% vs. 89%). The clinical success for moxifloxacin therapy (93%) was higher than that for amoxicillin/clavulanate ± clarithromycin (85%) [95% C.I. for the treatment difference was 2.9% to 13.2%].
The microbiological eradication rates (eradication plus presumed eradication) in moxifloxacin treated patients from these two trials were Streptococcus pneumoniae 93% (63/68), Streptococcus pneumoniae bacteremia 95% (19/20), Haemophilus influenzae 92% (23/25), Mycoplasma pneumoniae 96% (22/23), and Chlamydia pneumoniae 93% (13/14). Across all moxifloxacin tablet and intravenous community acquired pneumonia studies, the clinical success for Legionella pneumophila was 100% (6/6).
Acute bacterial sinusitis. In a large randomised, double-blind controlled study, moxifloxacin tablets (400 mg once daily for 10 days) were compared with cefuroxime axetil (250 mg twice daily for 10 days) in the treatment of acute bacterial sinusitis. The results obtained from this study are shown in Table 7.

Skin and skin structure infections. In a prospective, randomized, double-blind, active-control, multi-centre Phase III B clinical study (study number 100273), a total of 617 patients were randomized to one of the two treatment groups (sequential IV/p.o moxifloxacin 400 mg qd versus piperacillin/tazobactam 3.0/0.375 g IV followed by p.o amoxicillin/clavulanic acid suspension 800/114 mg bid). Subjects were enrolled with infections which included infected ischaemic or decubitus ulcers, diabetic foot infections, major abscesses, carbuncles, other SSTI requiring surgery, post-operative surgical infections and infected bite wounds. The clinical success rate (clinical cure or resolution) at the Test of Cure (TOC) visit was 79.4% (143/180) and 81.8% (153/187) for the moxifloxacin and comparator groups, respectively. Moxifloxacin was proven to be no less effective than the comparator regimen (-12.04, +3.29 95% CI).
In a second study prospective, non-blind, comparative, parallel group, multicentre, multinational Phase III clinical study (study number 10279) in patients with cSSSi with 804 patients, the patients were randomly and equally assigned to one of the two treatment groups: sequential IV/PO moxifloxacin 400 mg QD or amoxicillin/clavulanate 1000/200 mg IV followed by 500/125 mg PO TID, and maintained on a non-blind basis.
The clinical success rate at the TOC visit was 80.6% (254/315) and 84.5% (268/317) for the moxifloxacin and comparator groups respectively. Moxifloxacin was proven to be no less effective than the comparator regimen (-9.41, +2.18 95% CI).
The clinical cure rates for the patients at TOC visit analysed by diagnosis type for each study are shown in Table 8.

The bacteriological eradication rates at TOC by baseline pathogen for selected organisms in the patients with causative organisms are shown in Table 9.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration, moxifloxacin is absorbed rapidly and almost completely with an absolute bioavailability of approximately 90%.
Concomitant administration of moxifloxacin together with food slightly prolongs the time to reach peak concentrations by approximately 2 hours and slightly reduced peak concentrations by approximately 16%. Extent of absorption remained unchanged. As AUC/MIC is most predictive for antimicrobial efficacy of quinolones, this effect is clinically not relevant. Therefore, moxifloxacin can be administered independent from meals.
The mean (± SD) C_max and AUC values following single and multiple doses of 400 mg moxifloxacin given orally or by 1 hour i.v. infusion are summarised in Table 10 and Figure 1.

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

Distribution.

The mean volume of distribution at steady state (Vss) is approximately 2 L/kg. In in vitro and ex vivo experiments protein binding over a range of 0.02 to 2 mg/L resulted in a protein binding of approximately 40 - 42% independent of the drug concentration. Moxifloxacin is mainly bound to serum albumin.
Moxifloxacin is widely distributed throughout the body. Moxifloxacin has been detected in active form in the saliva, nasal and bronchial secretions, mucosa of the sinuses following oral or intravenous administration of 400 mg. Concentrations measured at 3 hours post-dose are summarised in Table 11. The rates of elimination of moxifloxacin from tissues generally parallel the elimination from plasma.

The peak concentrations and site vs. plasma concentration ratios for various target tissues yielded comparable results for both modes of drug administration after a single dose of 400 mg moxifloxacin.

Metabolism.

Moxifloxacin is metabolised via glucuronide and sulphate conjugation. The cytochrome P450 system is not involved in moxifloxacin metabolism and is not affected by moxifloxacin. M1 and M2 are the only metabolites relevant in humans and both are microbiologically inactive. The sulphate conjugate (M1) accounts for approximately 38% of the dose and is eliminated primarily in the faeces. Approximately 14% of an oral or intravenous dose is converted to 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.

Excretion.

Approximately 45% of an oral or intravenous dose 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 approximately 12 L/hr and 2.5 L/hr, respectively, suggesting partial tubular reabsorption of the drug from the kidneys.

Special populations.

Geriatric.

In a study of 16 healthy elderly male and female volunteers given a single oral 200 mg dose of moxifloxacin, the AUC, C_max and elimination half life were not statistically different between young and elderly subjects. In large phase III studies, the pharmacokinetics in elderly patients following intravenous infusion of 400 mg were similar to those observed in young patients. Therefore, dosage adjustments based on age are not necessary.