Consumer medicine information

Moxifloxacin Kabi

Moxifloxacin

BRAND INFORMATION

Brand name

Moxifloxacin Kabi

Active ingredient

Moxifloxacin

Schedule

What is in this leaflet

This leaflet answers some common questions about Moxifloxacin Kabi.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you receiving Moxifloxacin Kabi against the benefits they expect it will have for you.

If you have any concerns about receiving this medicine, ask your doctor or pharmacist.

Keep this leaflet in a safe place, even after your treatment is finished. You may need to read it again.

What Moxifloxacin Kabi is used for

Moxifloxacin Kabi is a sterile intravenous antibiotic used in adults for the treatment of serious infections of the lungs and airways. It can also be used to treat severe, complicated skin and skin structure infections.

Moxifloxacin Kabi is used to start the treatment and then your doctor may prescribe tablets to complete the course.

Remember to read the Consumer Medicine Information for Moxifloxacin tablets, if you receive them, because it may contain additional information specific to the tablets.

Moxifloxacin Kabi contains the active ingredient, moxifloxacin, which is an antibiotic belonging to a group of medicines called quinolones. These antibiotics work by killing the bacteria that are causing your infection.

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

Moxifloxacin Kabi is available by prescription only, and is used in a hospital environment only.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

Before you are given Moxifloxacin Kabi

When you must not be given it

You must not be given Moxifloxacin Kabi if you have an allergy to:

moxifloxacin, the active ingredient in Moxifloxacin Kabi
any of the ingredients listed at the end of this leaflet.
other medicines belonging to the quinolone family (e.g. ciprofloxacin, norfloxacin, nalidixic acid)

Some of the symptoms of an allergic reaction may include:

shortness of breath
wheezing or difficulty breathing
swelling of the face, lips, tongue or other parts of the body
rash, itching or hives on the skin

You should not be given Moxifloxacin Kabi if you:

have a condition called ‘QTc prolongation’ which is a type of abnormal heart rhythm
are taking medicines to treat arrhythmia - fast, slow or irregular heart beat (e.g. quinidine, procainamide, amiodarone, sotalol)
have a blood test that shows lower than normal potassium levels

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or think you may be pregnant. Moxifloxacin Kabi is not recommended if you are pregnant.

Tell your doctor if you are breastfeeding. Moxifloxacin Kabi passes into breast milk and may affect your baby.

Moxifloxacin Kabi should not be used in children under 18 years of age.

Tell your doctor if 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 disease causing muscle weakness)
have or have had a mental illness
have diabetes

Some medical conditions may require a restricted sodium intake (e.g. congestive heart failure, kidney failure, kidney disease). Tell your doctor if you have a condition like this because Moxifloxacin Kabi solution contains sodium salt. The additional sodium you receive may worsen the symptoms of these conditions.

If you have not told your doctor about any of the above, tell him/her before you are given Moxifloxacin Kabi.

Taking other medicines

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

Moxifloxacin Kabi may have an effect on the electro-cardiogram (ECG - an electrical record of the activity of the heart) and may add to the effect of other medicines on the ECG. You should advise your doctor if you are taking any medicines that might affect the heart rhythm.

In particular, tell your doctor if you are taking:

warfarin, a medicine 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, sotalol)
medicines that can affect the heart rhythm (e.g. erythromycin, tricyclic antidepressants, antipsychotics)
corticosteroids

These medicines and Moxifloxacin Kabi may affect each other or increase the chance of you getting a side effect.

Your doctor or pharmacist will be able to tell you what to do when receiving Moxifloxacin Kabi with other medicines.

How Moxifloxacin Kabi is given

Moxifloxacin Kabi is given as a slow injection into a vein over a period of 60 minutes (‘drip’).

Moxifloxacin Kabi must only be given by a doctor or a nurse.

How much is given

This depends on your condition, and will be prescribed by your doctor.

The usual adult dose is 400 mg once a day for 5-21 days.

How long it is given

Your doctor will determine the duration of time that you are given Moxifloxacin Kabi depending on your infection. Your doctor will put you on Moxifloxacin tablets as soon as possible, after being given Moxifloxacin Kabi injection.

If you are given too much (overdose)

Immediately tell your doctor or nurse or telephone the Poisons Information Centre (Australia: 13 11 26) or 0800 764 766 (New Zealand), or go to the Accident and Emergency department at your nearest hospital, if you think you or anyone else may have received too much Moxifloxacin Kabi. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are receiving Moxifloxacin Kabi

Things you must do

Tell your doctor or nurse if you develop an allergic reaction (e.g. skin rash) while on Moxifloxacin Kabi, even following a single dose.

If you develop diarrhoea, tell your doctor or pharmacist immediately. Do this even if it occurs several weeks after you have finished receiving Moxifloxacin Kabi. Diarrhoea may mean 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.

Tell your doctor immediately if you feel any discomfort, pain, swelling or inflammation of a tendon. Medicines like Moxifloxacin Kabi have been reported to cause tendon damage (especially the Achilles tendon). Elderly patients and those taking a type of medicine called corticosteroids are more at risk.

If you experience palpitations (fast or irregular heartbeats) or fainting spells during the period of treatment, tell your doctor immediately.

Tell your doctor or nurse if you experience symptoms of depression or self-endangering behavior. Moxifloxacin Kabi should be discontinued.

Tell your doctor or nurse if you develop photosensitivity (getting sunburnt very easily). Avoid exposure to ultraviolet radiation and sunlight. Protect your skin when you are in the sun, especially between 10am and 3pm. If you are outdoors, wear protective clothing and use a 30+ sunscreen.

Tell your doctor or nurse as soon as possible if you develop pain, burning tingling, numbness or weakness in any part of the body.

Things you must not do

Do not interfere with the equipment that is used to infuse Moxifloxacin Kabi into your body. Changes to the settings of the equipment must only be carried out by your doctor or the nurse who is looking after you.

Side Effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are receiving Moxifloxacin Kabi. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need to stop receiving the injection or have medical treatment if you get some of the serious side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following side effects and they worry you:

headache
dizziness or light-headedness
nausea, vomiting
stomach pains, diarrhoea
thrush in the mouth (sore creamy-yellow raised patches in mouth) or in the vagina (itching, burning or thick white discharge)
redness or pain at the site of injection

These are the more common side effects of Moxifloxacin Kabi. They are usually mild and short-lived.

Tell your doctor immediately, if you notice any of the following:

allergic reactions such as skin rashes, swelling of the face, lips, mouth or throat
palpitations or fainting spells
watery or bloody diarrhoea, even if it occurs several weeks after finishing your Moxifloxacin Kabi treatment
pain, swelling or rupture of a tendon
fits (seizures, convulsions)
visual disturbances (eyesight problems)
pain, burning, tingling, numbness or weakness that starts or worsens on Moxifloxacin Kabi
changes in your moods or thoughts that worry you

These are serious side effects. If you have them, you may need urgent medical attention, and Moxifloxacin Kabi will need to be discontinued.

Moxifloxacin Kabi may cause rapid and severe inflammation of the liver, which can lead to life-threatening liver failure including fatal cases. Tell your doctor immediately if you suddenly feel 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

If you develop a skin reaction or blistering and/or peeling of the skin and/or mucosal reactions contact your doctor immediately before you continue the treatment.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell. Other side effects not listed above may also occur in some people.

After recieving Moxifloxacin Kabi

Storage

Moxifloxacin Kabi will be stored in the pharmacy or on the ward. It is kept in a cool, dry place away from sunlight, where the temperature stays below 25°C and above 15°C. Do not refrigerate or freeze.

Disposal

Each pack of Moxifloxacin Kabi is to be used once only. Any unused portion must be returned to the pharmacist for disposal.

Product Description

What it looks like

Moxifloxacin Kabi 400 mg is a ready to use, clear yellow solution for infusion.

Moxifloxacin Kabi is available in Freeflex bags in packs of 1, 10, 20, 25 and 40.

It is also available in KabiPac bottles in packs of 1, 10, 20, 25 and 40.

Not all forms and pack sizes may be marketed.

Ingredients

Active Ingredient:

Moxifloxacin Kabi - moxifloxacin (as hydrochloride) 400 mg per 250 mL

Inactive ingredients:

sodium acetate trihydrate
sodium sulphate
sulphuric acid
water for injections

Supplier

Moxifloxacin Kabi is supplied in Australia by:

Fresenius Kabi Australia Pty Limited
Level 2, 2 Woodland Way
Mount Kuring-gai NSW 2080
Australia
Telephone: (02) 9391 5555

Moxifloxacin Kabi is supplied in New Zealand by:

Fresenius Kabi New Zealand Limited
60 Pavilion Drive
Airport Oaks, Auckland 2022
New Zealand
Freecall: 0800 144 892

Australian Registration Numbers

free flex® bag - AUST R 241252

KabiPac bottle - AUST R 241253

Date of preparation

July 2018

See TGA website (www.ebs.tga.gov.au) for latest Australian Consumer Medicine Information.

Published by MIMS September 2018

BRAND INFORMATION

Brand name

Moxifloxacin Kabi

Active ingredient

Moxifloxacin

Schedule

1 Name of Medicine

Moxifloxacin hydrochloride.

2 Qualitative and Quantitative Composition

Moxifloxacin Kabi is available in ready-to-use 250 mL (containing 400 mg of moxifloxacin) Freeflex bags or KabiPac infusion bottles, as a sterile, preservative free aqueous solution of moxifloxacin hydrochloride with pH ranging from 5.0 to 6.0. The appearance of the intravenous solution is yellow. The colour does not affect, nor is it indicative of, product stability. The inactive ingredients are sodium acetate trihydrate, sodium sulfate, sulfuric acid and water for injections.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Moxifloxacin Kabi (moxifloxacin hydrochloride) is a synthetic broad spectrum antibacterial agent and is available as Moxifloxacin Kabi IV infusion solution for intravenous administration.

4 Clinical Particulars

4.1 Therapeutic Indications

Moxifloxacin Kabi intravenous solutions are indicated for treatment of adults who require initial IV therapy for the treatment of infections in the conditions:
community acquired pneumonia (caused by susceptible organisms);
acute exacerbations of chronic bronchitis when caused by organisms bacteriologically proven to be resistant to other classes of antibiotics or when there is intolerance to other antibiotics;
Moxifloxacin Kabi intravenous solutions are indicated for treatment of adults with severe and complicated skin and skin structure infections who require initial parenteral therapy, and who have intolerance to alternative agents (especially penicillin allergy), and when caused by organisms known to be susceptible to moxifloxacin.
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 Kabi 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

The usual dose of Moxifloxacin Kabi is 400 mg intravenously every 24 hours. The recommended dose should not be exceeded. Moxifloxacin Kabi is recommended for the treatment of adults in its approved indications who require initial IV therapy (see Section 4.1 Therapeutic Indications). Initial intravenous treatment may be followed by oral treatment with moxifloxacin 400 mg tablets* when clinically indicated. The duration of therapy depends on the type of infection as described in Table 1.
* Moxifloxacin tablets are unavailable in Moxifloxacin Kabi brand however are available in other brands. Where the tablet formulation is clinically indicated, moxifloxacin tablets from other suppliers should be used.
The recommended duration of therapy for the treatment indication should not be exceeded.
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.

Directions to administer.

Moxifloxacin Kabi (moxifloxacin) should be administered by intravenous infusion only. It is not intended for intra-arterial, intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.
Moxifloxacin Kabi should be administered by intravenous infusion over a period of 60 minutes by direct infusion or through a Y-type intravenous infusion set which may already be in place. Caution: rapid or bolus intravenous infusion must be avoided.
Since only limited data are available on the compatibility of moxifloxacin intravenous injection with other intravenous substances, additives or other medications should not be added to Moxifloxacin Kabi or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of other drugs, the line should be flushed before and after infusion of Moxifloxacin Kabi with an infusion solution compatible with Moxifloxacin Kabi as well as with other drug(s) administered via this common line.
In patients for whom sodium intake is of medical concern (patients with congestive heart failure, renal failure, nephrotic syndrome etc.) the additional sodium load of the solution for infusion should be taken into account.
Parenteral medicine products should be inspected visually for particulate matter and discolouration prior to the administration. Only clear solution free from particles should be used.
Moxifloxacin Kabi is for single use in one patient only. Discard any residue. Contains no antimicrobial preservatives. Only clear solutions are to be used. To be used immediately after the bag or bottle is opened.

Compatible solutions for infusion.

Moxifloxacin Kabi is compatible with the following intravenous solutions at ratios from 1:10 to 10:1: 0.9% Sodium Chloride Injection, USP; 1 M Sodium Chloride Injection; 5% Glucose Injection, USP; Water for Injections, USP; 10% Glucose for Injection, USP; Glucose 40%; Lactated Ringer's Solution for Injection; Ringer's Solution; Xylitol 20%.
If the Y-type or "piggyback" method of administration is used, it is advisable to discontinue temporarily the administration of any other solutions during the infusion of Moxifloxacin Kabi.

Dose adjustments.

Elderly.

No adjustment of dose is necessary.

Paediatric.

The use of Moxifloxacin Kabi 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 Kabi 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 any component of moxifloxacin or to any other quinolone or any of the excipients.
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 4.4 Special Warnings and Precautions for Use, General, Paediatric use; Section 4.2 Dose and Method of Administration, Paediatric.

4.4 Special Warnings and Precautions for Use

[Oral moxifloxacin is unavailable in this brand however is available in other brands. Precaution information relating to the oral formulation of moxifloxacin is also included in the following sub-sections for completion and for information of the prescribers.]
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. These include, but are not limited to, serious adverse reactions involving the nervous system (see Psychiatric reactions) and musculoskeletal system (see Tendonitis and tendon rupture).

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, Use in lactation.

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 Torsades 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 Kabi. 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 Kabi 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 Kabi 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 Kabi should be discontinued.

Seizures.

Seizures may occur with quinolone therapy. Moxifloxacin Kabi 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 Kabi 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)).

Use in the elderly.

No data available.

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.

Effects on laboratory tests.

No data available.

Use in hepatic impairment.

As limited clinical data are available in severe hepatic impairment (Child Pugh C), the use of Moxifloxacin Kabi 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.

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 Kabi 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 Kabi 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.

Sodium content of solution for infusion.

In patients for whom sodium intake is of medical concern (patients with congestive heart failure, renal failure, nephrotic syndrome, etc.) the additional sodium load of the solution for infusion should be taken into account. The sodium content of the solution for infusion (250 mL) is 54.4 mmol.

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, Microbiology).
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 Kabi.

Information for patients.

To assure safe and effective use of Moxifloxacin Kabi, 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 Kabi;
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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

[Oral moxifloxacin is unavailable in this brand however is available in other brands. Information relating to interactions with other medicines obtained using oral moxifloxacin is also included in the following sub-sections for completion and for information of the prescribers.]

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 Kabi 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.
After intravenous drug administration carbo medicinalis only slightly reduces systemic exposure (approx. 20%).

Drug-drug interactions.

The potential for pharmacokinetic drug interactions between moxifloxacin and theophylline, warfarin, digoxin, probenecid, ranitidine, glibenclamide, 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 electrocardiogram. 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 Kabi 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)
[Category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.]
Reproductive studies performed in rats, rabbits and monkeys indicate that placental transfer of moxifloxacin occurs. Moxifloxacin was not teratogenic in Cynomolgous 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 Kabi, 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 Kabi may cause dizziness and lightheadedness; 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)

[Oral moxifloxacin is unavailable in this brand however is available in other brands. Information relating to adverse effects obtained using oral moxifloxacin is also included in the following sub-sections for completion and for information of the prescribers.]
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 Torsades 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.

Hypoglycemia.

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.

4.9 Overdose

Only limited data on overdose are available. In the event of overdosage it is recommended that appropriate supportive care should be instituted as dictated by the patient's clinical status. Due to the potential for moxifloxacin to cause QT prolongation, patients should be carefully monitored following an overdose.
For further advice on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia) or 0800 764 766 (New Zealand).

5 Pharmacological Properties

[Oral moxifloxacin is unavailable in this brand however it is available in other brands. Pharmacokinetic information obtained using oral moxifloxacin is also included in the following sub-sections for completion and for information for the prescribers.]

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology. 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 (see Table 3), both in vitro and in clinical infections (see Section 4.1 Therapeutic Indications).

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

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.
Community acquired pneumoniae.

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).
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 as follows in Table 5:

The bacteriological eradication rates at TOC by baseline pathogen for selected organisms in the patients with causative organisms follows in Table 6:

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 7. Also see 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 (V_ss) 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 summarized in Table 8. 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.