AVELOX 400/250 Mg/Ml Solution for Infusion

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
MOXIFLOXACIN HYDROCHLORIDE
Available from:
Bayer Limited
ATC code:
J01MA14
INN (International Name):
MOXIFLOXACIN HYDROCHLORIDE
Dosage:
400/250 Mg/Ml
Pharmaceutical form:
Solution for Infusion
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Fluoroquinolones
Authorization status:
Authorised
Authorization number:
PA1410/027/002
Authorization date:
2007-11-02

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Package leaflet: Information for the user

Avelox 400 mg/250 ml solution for infusion

For use in adults.

Moxifloxacin

Read all of this leaflet carefully before you start using this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

What Avelox is and what it is used for

What you need to know before you are administered Avelox

How to use Avelox

Possible side effects

How to store Avelox

Contents of the pack and other information

1.

What Avelox is and what it is used for

Avelox contains the active substance moxifloxacin which belongs to a group of antibiotics called

fluoroquinolones. Avelox works by killing bacteria that cause infections if they are caused by bacteria

that are susceptible to moxifloxacin.

Avelox is used in adults for treating the following bacterial infections:

Infection of the lungs (pneumonia) acquired outside the hospital

Infections of the skin and soft tissue

2.

What you need to know before you are administered Avelox

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

Do not use Avelox

If you are allergic to the active substance moxifloxacin, any other quinolone antibiotics or any

of the other ingredients of this medicine (listed in section 6).

If you are pregnant or breast-feeding.

If you are under 18 years of age.

If you have a history of tendon disease or disorder which was related to treatment with

quinolone antibiotics (see sections Warnings and precautions and 4. Possible side effects).

If you were born with or have had any condition with abnormal heart rhythm (seen on ECG,

electrical recording of the heart), have salt imbalance in the blood (especially low level of

potassium or magnesium in the blood), have a very slow heart rhythm (called ‘bradycardia’),

have a weak heart (heart failure), have a history of abnormal heart rhythms, or you are taking

other medicines that result in abnormal ECG changes (see section Other medicines and Avelox).

This is because Avelox can cause changes on the ECG, that is a prolongation of the QT-interval

i.e. delayed conduction of electrical signals.

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If you have a severe liver disease or liver enzymes (transaminases) that are higher than 5 times

the upper normal limit.

Warnings and precautions

Talk to your doctor before Avelox is administered for the first time

Avelox can change your heart’s ECG, especially if you are female, or if you are elderly. If you

are currently taking any medicine that decreases your blood potassium levels, consult your

doctor before Avelox is administered (see also sections Do not use Avelox and Other medicines

and Avelox).

If you suffer from epilepsy or a condition which makes you likely to have convulsions, tell

your doctor before Avelox is administered.

If you have or have ever had any mental health problems, consult your doctor before Avelox

is administered.

If you suffer from myasthenia gravis using Avelox may worsen the symptoms of your disease.

If you think you are affected consult your doctor immediately.

If you or any member of your family have glucose-6-phosphate dehydrogenase deficiency (a

rare hereditary disease), inform your doctor, who will advise whether Avelox is suitable for you.

Avelox should be given intravenously (in the vein) only, and should not be administered into an

artery.

When using Avelox

If you experience palpitations or irregular heart beat during the period of treatment, you

should inform your doctor immediately. He/she may wish to perform an ECG to measure your

heart rhythm.

The risk of heart problems may increase with increase of the dose and the speed of the

perfusion into your vein.

There is a rare chance that you may experience a severe, sudden allergic reaction (an

anaphylactic reaction/shock) even with the first dose, with symptoms that may include tightness

in the chest, feeling dizzy, feeling sick or faint, or experience dizziness on standing. If this

happens, treatment with Avelox solution for infusion has to be discontinued immediately.

Avelox may cause a rapid and severe inflammation of the liver which could lead to life-

threatening liver failure (including fatal cases, see section 4. Possible side effects). Please

contact your doctor before you continue the treatment if you suddenly start to feel unwell or

notice yellowing of the whites of the eyes, dark urine, itching of the skin, a tendency to bleed or

disturbances of thought or wakefulness.

If you develop a skin reaction or blistering and/or peeling of the skin and/or mucosal

reactions (see section 4. Possible side effects) contact your doctor immediately before you

continue the treatment.

Quinolone antibiotics, including Avelox, may cause convulsions. If this happens, treatment

with Avelox has to be discontinued.

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You may experience symptoms of nerve damage (neuropathy) such as pain, burning, tingling,

numbness and/or weakness especially in the feet and legs or hands and arms. If this happens,

inform your doctor immediately prior to continuing treatment with Avelox.

You may experience mental health problems even when taking quinolone antibiotics,

including Avelox, for the first time. In very rare cases depression or mental health problems

have led to suicidal thoughts and self-injurious behaviour such as suicide attempts (see section

4. Possible side effects). If you develop such reactions, treatment with Avelox has to be

discontinued.

You may develop diarrhoea whilst taking, or after taking, antibiotics including Avelox. If this

becomes severe or persistent or you notice that your stool contains blood or mucus you should

stop using Avelox immediately and consult your doctor. In this situation, you should not take

medicines that stop or slow down bowel movement.

Avelox may cause pain and inflammation of your tendons, even within 48 hours of starting

treatment and up to several months after discontinuing Avelox therapy. The risk of

inflammation and rupture of tendons is increased if you are elderly or if you are currently being

treated with corticosteroids. At the first sign of any pain or inflammation you should stop using

Avelox, rest the affected limb(s) and consult your doctor immediately. Avoid any unnecessary

exercise, as this might increase the risk of a tendon rupture (see sections Do not use Avelox and

4. Possible side effects).

If you are elderly with existing kidney problems take care that your fluid intake is sufficient

because dehydration may increase the risk of kidney failure

If your eyesight becomes impaired or if your eyes seem to be otherwise affected, consult an

eye specialist immediately (see sections Driving and using machines and 4. Possible side

effects).

Fluoroquinolone antibiotics may cause disturbances in blood sugar, including both a decrease

in blood sugar below normal levels (hypoglycemia) and an increase in blood sugar above

normal levels (hyperglycemia). In patients treated with Avelox, disturbances in blood sugar

occured predominantly in elderly patients receiving concomitant treatment with oral antidiabetic

medicines that lower blood sugar (e. g. sulfonylurea) or with insulin. If you suffer from

diabetes, your blood sugar should be carefully monitored (see section 4. Possible side effects).

Quinolone antibiotics may make your skin become more sensitive to sunlight or UV light.

You should avoid prolonged exposure to sunlight or strong sunlight and should not use a sunbed

or any other UV lamp while using Avelox.

There is limited experience on use of sequential intravenous/oral Avelox for the treatment of

infection of the lungs (pneumonia) acquired outside the hospital.

The efficacy of Avelox in the treatment of severe burns, infections of deep tissue and diabetic

foot infections with osteomyelitis (infections of the bone marrow) has not been established.

Children and adolescents

This medicine must not be administered to children and adolescents under the age of 18 because

efficacy and safety have not been established for this age group (see section Do not use Avelox).

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Other medicines and Avelox

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines

besides Avelox.

For Avelox, be aware of the following:

If you are using Avelox and other medicines that affect your heart there is an increased risk for

altering your heart rhythm. Therefore, do not use Avelox together with the following medicines:

Medicines that belong to the group of anti-arrhythmics (e.g. quinidine, hydroquinidine,

disopyramide, amiodarone, sotalol, dofetilide, ibutilide), antipsychotics (e.g. phenothiazines,

pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressants, some antimicrobials

(e.g. saquinavir, sparfloxacin, intravenous erythromycin, pentamidine, antimalarials particularly

halofantrine), some antihistamines (e.g. terfenadine, astemizole, mizolastine), and other

medicines (e.g. cisapride, intravenous vincamine, bepridil and diphemanil).

You must tell your doctor if you are taking other medicines that can lower your blood potassium

levels (e.g. some diuretics, some laxatives and enemas [large doses] or corticosteroids [anti-

inflammatory drugs], amphotericin B) or cause a slow heart rate because these can also increase

the risk of serious heart rhythm disturbances while using Avelox.

If you are currently taking oral anti-coagulants (e.g. warfarin), it may be necessary for your

doctor to monitor your blood clotting times.

Avelox with food and drink

The effect of Avelox is not influenced by food including dairy products.

Pregnancy, breast-feeding and fertility

Do not use Avelox if you are pregnant or breast-feeding.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor or pharmacist for advice before using this medicine.

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

Driving and using machines

Avelox may make you feel dizzy or light-headed, you may experience a sudden, transient loss of

vision, or you might faint for a short period. If you are affected in this way do not drive or operate

machinery.

Avelox contains sodium

This medicinal product contains 787 milligram (approximately 34 millimol) sodium per dose. To be

taken into consideration by patients on a controlled sodium diet.

3.

How to use Avelox

Avelox will always be given to you by a doctor or healthcare professional.

The recommended dose for adults is one bag once daily.

Avelox is for intravenous use. Your doctor should ensure that the infusion is given at a constant flow

over 60 minutes.

No adjustment of the dose is required in elderly patients, patients with a low bodyweight or in patients

with kidney problems.

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Your doctor will decide on the duration of your treatment with Avelox. In some cases your doctor may

start your treatment with Avelox solution for infusion and then continue your treatment with Avelox

tablets.

The duration of treatment depends upon the type of infection, and how well you respond to treatment

but the recommended durations of use are:

Infection of the lungs (pneumonia) acquired outside the hospital

7 - 14 days

Most patients with pneumonia were switched to oral treatment with Avelox tablets within 4 days.

Infections of the skin and soft tissue

7 - 21 days

For patients with complicated skin and skin structure infections the mean duration of intravenous

treatment was approximately 6 days and the average overall duration of treatment (infusion followed

by tablets) was 13 days.

It is important that you complete the course of treatment, even if you begin to feel better after a few

days. If you stop using this medicine too soon your infection may not be completely cured, the

infection may return or your condition may get worse, and you may also create a bacterial resistance to

the antibiotic.

The recommended dose and duration of treatment should not be exceeded (see section 2. What you

need to know before you are administered Avelox, Warnings and precautions).

If you receive more Avelox than you should

If you are concerned that you may have received too much Avelox, contact your doctor immediately.

If you miss a dose of Avelox

If you are concerned that you may have missed a dose of Avelox, contact your doctor immediately.

If you stop using Avelox

If the treatment with this medicine is stopped too soon your infection may not be completely cured.

Consult your doctor if you wish to stop the treatment with Avelox solution for infusion or Avelox

tablets before the end of the course of treatment.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The most serious side effects observed during the treatment with Avelox are listed below:

If you notice

an abnormal fast heart rhythm (rare side effect)

that you suddenly start feeling unwell or notice yellowing of the whites of the eyes, dark urine,

itching of the skin, a tendency to bleed or disturbances of thought or wakefulness (these can be

signs and symptoms of fulminant inflammation of the liver potentially leading to life-threating

liver failure (very rare side effect, fatal cases have been observed))

alterations of the skin and mucous membranes like painful blisters in the mouth/nose or at the

penis/vagina (Stevens-Johnson syndrome or toxic epidermal necrolysis) (very rare side effects,

potentially life threatening)

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inflammation of blood vessels (signs could be red spots on your skin, usually on your lower legs

or effects like joint pain) (very rare side effect)

a severe, sudden generalised allergic reaction incl. very rarely a life-threatening shock (e.g.

difficulty in breathing, drop of blood pressure, fast pulse) (rare side effect)

swelling incl. swelling of the airway (rare side effect, potentially life-threatening)

convulsions (rare side effect)

troubles associated with the nervous system such as pain, burning, tingling, numbness and/or

weakness in extremities (rare side effect)

depression (in very rare cases leading to self-harm, such as suicidal ideations/thoughts, or

suicide attempts) (rare side effect)

insanity (potentially leading to self-harm, such as suicidal ideations/thoughts, or suicide

attempts) (very rare side effect)

severe diarrhoea containing blood and/or mucus (antibiotic associated colitis incl.

pseudomembranous colitis), which in very rare circumstances, may develop into complications

that are life-threatening (rare side effects)

pain and swelling of the tendons (tendonitis) (rare side effect) or a tendon rupture (very rare side

effect)

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

In addition, if you notice

transient loss of vision (very rare side effect),

contact an eye specialist immediately.

If you have experienced life-threatening irregular heart beat (Torsade de Pointes) or stopping of heart

beat while taking Avelox (very rare side effects), tell your treating doctor immediately that you

have taken Avelox and do not restart the treatment.

A worsening of the symptoms of myasthenia gravis has been observed in very rare cases. If this

happens, consult your doctor immediately.

If you suffer from diabetes and you notice that your blood sugar is increased or decreased (rare or very

rare side effect), inform your doctor immediately.

If you are elderly with existing kidney problems and you notice decrease in urine output, swelling in

your legs, ankles or feet, fatigue, nausea, drowsiness, shortness of breath or confusion (these can be

signs and symptoms of kidney failure, a rare side effect), consult your doctor immediately.

Other side effects which have been observed during treatment with Avelox are listed below by how

likely they are:

Common (may affect up to 1 in 10 people)

nausea

diarrhoea

dizziness

stomach and abdominal ache

vomiting

headache

increase of a special liver enzyme in the blood (transaminases)

infections caused by resistant bacteria or fungi e.g. oral and vaginal infections caused by

Candida

pain or inflammation at injection site

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change of the heart rhythm (ECG) in patients with low blood potassium level

Uncommon (may affect up to 1 in 100 people)

rash

stomach upset (indigestion/heartburn)

changes in taste (in very rare cases loss of taste)

sleep problems (predominantly sleeplessness)

increase of a special liver enzyme in the blood (gamma-glutamyl-transferase and/or alkaline

phosphatase)

low number of special white blood cells (leukocytes, neutrophils)

constipation

itching

sensation of dizziness (spinning or falling over)

sleepiness

wind

change of the heart rhythm (ECG)

impaired liver function (incl. increase of a special liver enzyme in the blood (LDH))

decreased appetite and food intake

low white blood cells count

aches and pains such as back, chest, pelvic and extremities pains

increase of special blood cells necessary for blood clotting

sweating

increased specialised white blood cells (eosinophils)

anxiety

feeling unwell (predominantly weakness or tiredness)

shaking

joint pain

palpitations

irregular and fast heart beat

difficulty in breathing incl. asthmatic conditions

increase of a special digestive enzyme in the blood (amylase)

restlessness / agitation

tingling sensation (pins and needles) and/or numbness

skin hives

widening of blood vessels

confusion and disorientation

decrease of special blood cells necessary for blood clotting

visual disturbances incl. double and blurred vision

decreased blood clotting

increased blood lipids (fats)

low red blood cell count

muscle pain

allergic reaction

increase of bilirubin in the blood

inflammation of a vein

inflammation of the stomach

dehydration

severe heart rhythm abnormalities

dry skin

angina pectoris

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

muscle twitching

muscle cramp

hallucination

high blood pressure

swelling (of the hands, feet, ankles, lips, mouth, throat)

low blood pressure

kidney impairment (incl. increase in special kidney laboratory test results like urea and

creatinine)

inflammation of the liver

inflammation of the mouth

ringing/noise in the ears

jaundice (yellowing of the whites of the eyes or skin)

impairment of skin sensation

abnormal dreams

disturbed concentration

difficulty in swallowing

changes in smell (incl. loss of smell)

balance disorder and poor co-ordination (due to dizziness)

partial or total loss of memory

hearing impairment including deafness (usually reversible)

increased blood uric acid

emotional instability

impaired speech

fainting

muscle weakness

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

inflammation of joints

abnormal heart rhythms

increase of skin sensitivity

a feeling of self-detachment (not being yourself)

increased blood clotting

muscle rigidity

significant decrease of special white blood cells (agranulocytosis)

The following symptoms have been observed more frequently in patients treated intravenously:

Common (may affect up to 1 in 10 people)

Increase of a special liver enzyme in the blood (gamma-glutamyl-transferase)

Uncommon (may affect up to 1 in 100 people)

severe diarrhoea containing blood and/or mucus (antibiotic associated colitis) which in very rare

circumstances, may develop into complications that are life-threatening

abnormal fast heart rhythm

hallucination

low blood pressure

kidney impairment (incl. increase in special kidney laboratory test results like urea and

creatinine)

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kidney failure

swelling (of the hands, feet, ankles, lips, mouth, throat)

convulsions

Furthermore, there have been very rare cases of the following side effects reported following treatment

with other quinolone antibiotics, which might possibly also occur during treatment with Avelox:

increased blood sodium levels, increased blood calcium levels, a special type of reduced red blood cell

count (haemolytic anaemia), muscle reactions with muscle cell damage, increased sensitivity of the

skin to sunlight or UV light.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. You can also report side effects directly via HPRA Pharmacovigilance,

Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website:

www.hpra.ie; E-mail: medsafety@hpra.ie. By reporting side effects you can help provide more

information on the safety of this medicine.

5.

How to store Avelox

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

Do not use this medicine after the expiry date which is stated on the label of the bag and on the carton.

The expiry date refers to the last day of that month.

Do not store below 15°C.

Use immediately after first opening and/or dilution.

This product is for single use only. Any unused solution should be discarded.

At cool storage temperatures precipitation may occur, which will re-dissolve at room temperature.

Do not use this medicine if you notice any visible particulate matter or if the solution is cloudy.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Avelox contains

The active substance is moxifloxacin. Each bag contains 400 milligram moxifloxacin (as

hydrochloride). 1 milliliter contains 1.6 milligram moxifloxacin (as hydrochloride).

The other ingredients are sodium chloride, hydrochloric acid 1 N (for pH-adjustment), sodium

hydroxide solution 2 N (for pH-adjustment) and water for injections (see section Avelox

contains sodium).

What Avelox looks like and contents of the pack

Avelox is a clear, yellow solution for infusion.

Avelox is packaged in cartons containing 250 milliliter polyolefine bags with polypropylene port

sealed in aluminium foil overwrap. Packs of 5 and 12 bags are available.

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Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation holder:

Bayer Limited,

The Atrium,

Blackthorn Road,

Dublin 18

Manufacturer:

Bayer AG

D-51368 Leverkusen

Germany

This medicinal product is authorised in the Member States of the EEA under the following

names:

Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, Greece, Hungary, Ireland,

Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Slovak Republic, Slovenia,

Sweden, United Kingdom: Avelox

France: Izilox

Germany, Italy: Avalox

This leaflet was last revised in May 2017

Product Authorisation Number: 1410/27/2

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The following information is intended for healthcare professionals only:

Avelox can be administered via a T-tube together with the following solutions:

Water for injections, sodium chloride 0.9%, sodium chloride 1 molar, glucose 5%/10%/40%,

Xylitol 20%, Ringer’s solution, compound sodium lactate solution (Hartmann’s solution, Ringer-

lactate solution).

Avelox should not be co-infused with other drugs.

The following solutions were incompatible with Avelox:

Sodium chloride 10% and 20% solutions,

Sodium bicarbonate 4.2% and 8.4% solutions

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Avelox 400 mg/250 ml solution for infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 bag of 250 ml contains 400 mg moxifloxacin (as hydrochloride).

1 ml contains 1.6 mg moxifloxacin (as hydrochloride).

Excipient with known effect: 250 ml of solution for infusion contains 787 mg (34 mmol) sodium.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for infusion

Clear, yellow solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Avelox is indicated for the treatment of:

Community acquired pneumonia (CAP)

Complicated skin and skin structure infections (cSSSI)

Moxifloxacin should be used only when it is considered inappropriate to use antibacterial agents that

are commonly

recommended for the initial treatment of these infections.

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

4.2 Posology and method of administration

Posology

The recommended dose is 400 mg moxifloxacin, infused once daily.

Initial intravenous treatment may be followed by oral treatment with moxifloxacin 400 mg tablets, when clinically

indicated.

In clinical studies most patients switched to oral therapy within 4 days (CAP) or 6 days (cSSSI). The recommended

total duration of intravenous and oral treatment is 7 - 14 days for CAP and 7 - 21 days for cSSSI.

Renal/hepatic impairment

No adjustment of dosage is required in patients with mild to severely impaired renal function or in patients on chronic

dialysis i.e. haemodialysis and continuous ambulatory peritoneal dialysis (see section 5.2 for more details).

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

Other special populations

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

Paediatric population

Moxifloxacin is contraindicated in children and growing adolescents. Efficacy and safety of moxifloxacin in children

and adolescents have not been established (see section 4.3).

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Method of administration

For intravenous use; constant infusion over 60 minutes (see also section 4.4).

If medically indicated the solution for infusion can be administered via a T-tube, together with compatible infusion

solutions (see section 6.6).

4.3 Contraindications

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

Pregnancy and lactation (see section 4.6).

Patients below 18 years of age.

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

Both in preclinical investigations and in humans, changes in cardiac electrophysiology have been observed following

exposure to moxifloxacin, in the form of QT prolongation. For reasons of drug safety, moxifloxacin is therefore

contraindicated in patients with:

Congenital or documented acquired QT prolongation

Electrolyte disturbances, particularly in uncorrected hypokalaemia

Clinically relevant bradycardia

Clinically relevant heart failure with reduced left-ventricular ejection fraction

Previous history of symptomatic arrhythmias

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

Due to limited clinical data, moxifloxacin is also contraindicated in patients with impaired liver function (Child Pugh

C) and in patients with transaminases increase > 5fold ULN.

4.4 Special warnings and precautions for use

The benefit of moxifloxacin treatment especially in infections with a low degree of severity should be balanced with

the information contained in the warnings and precautions section.

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

Moxifloxacin has been shown to prolong the QTc interval on the electrocardiogram in some patients. The magnitude

of QT prolongation may increase with increasing plasma concentrations due to rapid intravenous infusion. Therefore,

the duration of infusion should not be less than the recommended 60 minutes and the intravenous dose of 400 mg

once a day should not be exceeded. For more details see below and refer to sections 4.3 and 4.5.

Treatment with moxifloxacin should be stopped if signs or symptoms that may be associated with cardiac arrhythmia

occur during treatment, with or without ECG findings.

Moxifloxacin should be used with caution in patients with any condition pre-disposing to cardiac arrhythmias (e.g.

acute myocardial ischaemia) because they may have an increased risk of developing ventricular arrhythmias (incl.

torsade de pointes) and cardiac arrest. See also sections 4.3 and 4.5.

Moxifloxacin should be used with caution in patients who are taking medications that can reduce potassium levels. See

also sections 4.3 and 4.5.

Moxifloxacin should be used with caution in patients who are taking medications associated with clinically significant

bradycardia. See also section 4.3.

Female patients and elderly patients may be more sensitive to the effects of QTc-prolonging medications such as

moxifloxacin and therefore special caution is required.

Hypersensitivity/allergic reactions

Hypersensitivity and allergic reactions have been reported for fluoroquinolones including moxifloxacin after first

administration. Anaphylactic reactions can progress to a life-threatening shock, even after the first administration. In

cases of clinical manifestations of severe hypersensitivity reactions moxifloxacin should be discontinued and suitable

treatment (e.g. treatment for shock) initiated.

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Severe liver disorders

Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with

moxifloxacin (see section 4.8). Patients should be advised to contact their doctor prior to continuing treatment if signs

and symptoms of fulminant hepatic disease develop such as rapidly developing asthenia associated with jaundice, dark

urine, bleeding tendency or hepatic encephalopathy.

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

Serious bullous skin reactions

Cases of bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with

moxifloxacin (see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing

treatment if skin and/or mucosal reactions occur.

Patients predisposed to seizures

Quinolones are known to trigger seizures. Use should be with caution in patients with CNS disorders or in the presence

of other risk factors which may predispose to seizures or lower the seizure threshold. In case of seizures, treatment with

moxifloxacin should be discontinued and appropriate measures instituted.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoaesthesias, dysaesthesias, or weakness

have been reported in patients receiving quinolones including moxifloxacin. Patients under treatment with

moxifloxacin should be advised to inform their doctor prior to continuing treatment if symptoms of neuropathy such as

pain, burning, tingling, numbness, or weakness develop in order to prevent the development of an irreversible condition

(see section 4.8).

Psychiatric reactions

Psychiatric reactions may occur even after the first administration of quinolones, including moxifloxacin. In very rare

cases depression or psychotic reactions have progressed to suicidal thoughts and self-injurious behaviour such as

suicide attempts (see section 4.8). In the event that the patient develops these reactions, moxifloxacin should be

discontinued and appropriate measures instituted. Caution is recommended if moxifloxacin is to be used in psychotic

patients or in patients with history of psychiatric disease.

Antibiotic-associated diarrhoea incl. colitis

Antibiotic-associated diarrhoea (AAD) and antibiotic-associated colitis (AAC), including pseudomembranous colitis

and Clostridium difficile-associated diarrhoea, has been reported in association with the use of broad spectrum

antibiotics including moxifloxacin and may range in severity from mild diarrhoea to fatal colitis. Therefore it is

important to consider this diagnosis in patients who develop serious diarrhoea during or after the use of moxifloxacin.

If AAD or AAC is suspected or confirmed, ongoing treatment with antibacterial agents, including moxifloxacin, should

be discontinued and adequate therapeutic measures should be initiated immediately. Furthermore, appropriate infection

control measures should be undertaken to reduce the risk of transmission. Drugs inhibiting peristalsis are

contraindicated in patients who develop serious diarrhoea.

Patients with myasthenia gravis

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

exacerbated.

Tendon inflammation, tendon rupture

Tendon inflammation and rupture (especially Achilles tendon), sometimes bilateral, may occur with quinolone therapy

including moxifloxacin, even within 48 hours of starting treatment and have been reported up to several months after

discontinuation of therapy. The risk of tendinitis and tendon rupture is increased in elderly patients and in those treated

concurrently with corticosteroids. At the first sign of pain or inflammation, patients should discontinue treatment with

moxifloxacin, rest the affected limb(s) and consult their doctor immediately in order to initiate appropriate treatment

(e.g. immobilisation) for the affected tendon (see sections 4.3 and 4.8).

Patients with renal impairment

Elderly patients with renal disorders should use moxifloxacin with caution if they are unable to maintain adequate fluid

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intake, because dehydration may increase the risk of renal failure.

Vision disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted

immediately (see sections 4.7 and 4.8).

Dysglycemia

As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have

been reported with moxifloxacin. In moxifloxacin-treated patients, dysglycemia occurred predominantly in elderly

diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g. sulfonylurea) or with insulin.

In diabetic patients, careful monitoring of blood glucose is recommended (see section 4.8).

Prevention of photosensitivity reactions

Quinolones have been shown to cause photosensitivity reactions in patients. However, studies have shown that

moxifloxacin has a lower risk to induce photosensitivity. Nevertheless patients should be advised to avoid exposure to

either UV irradiation or extensive and/or strong sunlight during treatment with moxifloxacin.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with a family history of or actual glucose-6-phosphate dehydrogenase deficiency are prone to haemolytic

reactions when treated with quinolones. Therefore, moxifloxacin should be used with caution in these patients.

Peri-arterial tissue inflammation

Moxifloxacin solution for infusion is for intravenous administration only. Intra-arterial administration should be

avoided since preclinical studies demonstrated peri-arterial tissue inflammation following infusion by this route.

Patients with special cSSSI

Clinical efficacy of moxifloxacin in the treatment of severe burn infections, fasciitis and diabetic foot infections with

osteomyelitis has not been established.

Patients on sodium diet

This medicinal product contains 787 mg (approximately 34 mmol) sodium per dose. To be taken into consideration by

patients on a controlled sodium diet.

Interference with biological tests

Moxifloxacin therapy may interfere with the Mycobacterium spp. culture test by suppression of mycobacterial growth

causing false negative results in samples taken from patients currently receiving moxifloxacin.

Patients with MRSA infections

Moxifloxacin is not recommended for the treatment of MRSA infections. In case of a suspected or confirmed infection

due to MRSA, treatment with an appropriate antibacterial agent should be started (see section 5.1).

Paediatric population

Due to adverse effects on the cartilage in juvenile animals (see section 5.3) the use of moxifloxacin in children and

adolescents < 18 years is contraindicated (see section 4.3).

4.5 Interaction with other medicinal products and other forms of interaction

Interactions with medicinal products

An additive effect on QT interval prolongation of moxifloxacin and other medicinal products that may prolong the QTc

interval cannot be excluded. This might lead to an increased risk of ventricular arrhythmias, including torsade de

pointes. Therefore, co-administration of moxifloxacin with any of the following medicinal products is contraindicated

(see also section 4.3):

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

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

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

tricyclic antidepressive agents

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

halofantrine)

certain antihistaminics (terfenadine, astemizole, mizolastine)

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

Moxifloxacin should be used with caution in patients who are taking medication that can reduce potassium levels (e.g.

loop and thiazide-type diuretics, laxatives and enemas [high doses], corticosteroids, amphotericin B) or medication that

is associated with clinically significant bradycardia.

After repeated dosing in healthy volunteers, moxifloxacin increased C

of digoxin by approximately 30% without

affecting AUC or trough levels. No precaution is required for use with digoxin.

In studies conducted in diabetic volunteers, concomitant administration of oral moxifloxacin with glibenclamide

resulted in a decrease of approximately 21% in the peak plasma concentrations of glibenclamide. The combination of

glibenclamide and moxifloxacin could theoretically result in a mild and transient hyperglycaemia. However, the

observed pharmacokinetic changes for glibenclamide did not result in changes of the pharmacodynamic parameters

(blood glucose, insulin). Therefore no clinically relevant interaction was observed between moxifloxacin and

glibenclamide.

Changes in INR

A large number of cases showing an increase in oral anticoagulant activity have been reported in patients receiving

antibacterial agents, especially fluoroquinolones, macrolides, tetracyclines, cotrimoxazole and some cephalosporins.

The infectious and inflammatory conditions, age and general status of the patient appear to be risk factors. Under these

circumstances, it is difficult to evaluate whether the infection or the treatment caused the INR (international normalised

ratio) disorder. A precautionary measure would be to more frequently monitor the INR. If necessary, the oral

anticoagulant dosage should be adjusted as appropriate.

Clinical studies have shown no interactions following concomitant administration of moxifloxacin with: ranitidine,

probenecid, oral contraceptives, calcium supplements, morphine administered parenterally, theophylline, cyclosporine

or itraconazole.

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

interaction via cytochrome P450 enzymes is unlikely.

Interaction with food

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

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of moxifloxacin in human pregnancy has not been evaluated. Animal studies have shown reproductive

toxicity (see section 5.3). The potential risk for humans is unknown. Due to the experimental risk of damage by

fluoroquinolones to the weight-bearing cartilage of immature animals and reversible joint injuries described in children

receiving some fluoroquinolones, moxifloxacin must not be used in pregnant women (see section 4.3).

Breast-feeding

There is no data available in lactating or nursing women. Preclinical data indicate that small amounts of moxifloxacin

are secreted in milk. In the absence of human data and due to the experimental risk of damage by fluoroquinolones to

the weight-bearing cartilage of immature animals, breast-feeding is contraindicated during moxifloxacin therapy (see

section 4.3).

Fertility

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

4.7 Effects on ability to drive and use machines

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No studies on the effects of moxifloxacin on the ability to drive and use machines have been performed.

However,

fluoroquinolones including moxifloxacin may result

in an impairment

the patient's ability to drive or

operate

machinery due to CNS reactions (e.g.

dizziness;

acute, transient

loss of vision, see section 4.8) or acute and short

lasting loss

consciousness

(syncope,

see section 4.8).

Patients

should be advised to see how they react

moxifloxacin before driving or operating machinery.

4.8 Undesirable effects

Adverse reactions observed in clinical trials and derived from post-marketing reports with moxifloxacin 400 mg daily

administered by the intravenous or oral route (intravenous only, sequential [IV/oral] and oral administration) sorted by

frequencies are listed below:

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

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are

defined as:

common (

1/100 to < 1/10)

uncommon (

1/1,000 to < 1/100)

rare (

1/10,000 to < 1/1,000)

very rare (< 1/10,000)

System Organ

Class

(MedDRA)

Common

Uncommon

Rare

Very Rare

Infections and

infestations

Superinfections

due to resistant

bacteria or

fungi e.g. oral

and vaginal

candidiasis

Blood and

lymphatic

system

disorders

Anaemia

Leucopenia(s)

Neutropenia

Thrombocytopenia

Thrombocythemia

Blood eosinophilia

Prothrombin time

prolonged/INR

increased

Prothrombin level

increased/INR

decreased

Agranulocytosis

Immune system

disorders

Allergic reaction

(see section 4.4)

Anaphylaxis

incl. very rarely

life-threatening

shock (see

section 4.4)

Allergic oedema/

angiooedema

(incl. laryngeal

oedema,

potentially life-

threatening, see

section 4.4)

Metabolism

and nutrition

disorders

Hyperlipidemia

Hyperglycemia

Hyperuricemia

Hypoglycemia

Psychiatric

Anxiety reactions

Emotional

Depersonalization

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disorders

Psychomotor

hyperactivity/

agitation

lability

Depression (in

very rare cases

potentially

culminating in

self- injurious

behaviour, such

as suicidal

ideations/

thoughts, or

suicide attempts,

see section 4.4)

Hallucination

Psychotic

reactions

(potentially

culminating in

self- injurious

behaviour, such

as suicidal

ideations/

thoughts, or

suicide attempts,

see section 4.4)

Nervous system

disorders

Headache

Dizziness

Par- and

Dysaesthesia

Taste disorders

(incl. ageusia in

very rare cases)

Confusion and

disorientation

Sleep disorders

(predominantly

insomnia)

Tremor

Vertigo

Somnolence

Hypoaesthesia

Smell disorders

(incl. anosmia)

Abnormal

dreams

Disturbed

coordination

(incl. gait

disturbances,

esp. due to

dizziness or

vertigo)

Seizures incl.

grand mal

convulsions (see

section 4.4)

Disturbed

attention

Speech disorders

Amnesia

Peripheral

neuropathy and

polyneuropathy

Hyperaesthesia

Eye disorders

Visual

disturbances incl.

diplopia and

blurred vision

(especially in the

course of CNS

reactions, see

section 4.4)

Transient loss of

vision (especially

in the course of

CNS reactions,

see sections 4.4

and 4.7)

Ear and

labyrinth

disorders

Tinnitus

Hearing

impairment incl.

deafness (usually

reversible)

Cardiac

disorders

prolongation in

patients with

hypokalaemia

(see sections

4.3 and 4.4)

QT prolongation

(see section 4.4)

Palpitations

Tachycardia

Atrial fibrillation

Angina pectoris

Ventricular

tachyarrhythmias

Syncope (i.e.,

acute and short

lasting loss of

consciousness)

Unspecified

arrhythmias

Torsade de

Pointes (see

section 4.4)

Cardiac arrest

(see section 4.4)

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Vascular

disorders

Vasodilatation

Hypertension

Hypotension

Vasculitis

Respiratory,

thoracic and

mediastinal

disorders

Dyspnea

(including

asthmatic

conditions)

Gastrointestinal

disorders

Nausea

Vomiting

Gastrointestinal

and abdominal

pains

Diarrhoea

Decreased appetite

and food intake

Constipation

Dyspepsia

Flatulence

Gastritis

Increased amylase

Dysphagia

Stomatitis

Antibiotic-

associated colitis

(incl. pseudo-

membranous

colitis, in very

rare cases

associated with

life-threatening

complications,

see section 4.4)

Hepatobiliary

disorders

Increase in

transaminases

Hepatic

impairment (incl.

LDH increase)

Increased bilirubin

Increased gamma-

glutamyl-

transferase

Increase in blood

alkaline

phosphatase

Jaundice

Hepatitis

(predominantly

cholestatic)

Fulminant

hepatitis

potentially

leading to life-

threatening liver

failure (incl. fatal

cases, see section

4.4)

Skin and

subcutaneous

tissue disorders

Pruritus

Rash

Urticaria

Dry skin

Bullous skin

reactions like

Stevens-Johnson

syndrome or toxic

epidermal

necrolysis

(potentially life-

threatening, see

section 4.4)

Musculoskeletal

and connective

tissue disorders

Arthralgia

Myalgia

Tendonitis (see

section 4.4)

Muscle cramp

Muscle

twitching

Muscle

weakness

Tendon rupture

(see section 4.4)

Arthritis

Muscle rigidity

Exacerbation of

symptoms of

myasthenia gravis

(see section 4.4)

Renal and

urinary

disorders

Dehydration

Renal

impairment (incl.

increase in BUN

and creatinine)

Renal failure

(see section 4.4)

General

disorders and

administration

site conditions

Injection and

infusion site

reactions

Feeling unwell

(predominantly

asthenia or

fatigue)

Painful conditions

Oedema

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The following undesirable effects have a higher frequency category in the subgroup of IV treated patients with or

without subsequent oral therapy:

Common:

Increased gamma-glutamyl-transferase

Uncommon:

Ventricular tachyarrhythmias, hypotension, oedema, antibiotic-associated colitis (incl.

pseudomembranous colitis, in very rare cases associated with life-threatening complications, see

section 4.4), seizures incl. grand mal convulsions (see section 4.4), hallucination, renal impairment

(incl. increase in BUN and creatinine), renal failure (see section 4.4)

There have been very rare cases of the following side effects reported following treatment with other fluoroquinolones,

which might possibly also occur during treatment with moxifloxacin: hypernatraemia, hypercalcaemia, haemolytic

anaemia, rhabdomyolysis, photosensitivity reactions (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any

suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971;

Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9 Overdose

No specific countermeasures after accidental overdose are recommended. In the event of overdose, symptomatic

treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval

prolongation. Concomitant administration of charcoal with a dose of 400 mg oral or intravenous moxifloxacin will

reduce systemic availability of the drug by more than 80% or 20% respectively. The use of charcoal early during

absorption may be useful to prevent excessive increase in the systemic exposure to moxifloxacin in cases of oral

overdose.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Quinolone antibacterials, fluoroquinolones, ATC code: J01MA14

Mechanism of action

Moxifloxacin inhibits bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) that are required for

bacterial DNA replication, transcription and repair.

PK/PD

Fluoroquinolones exhibit a concentration dependent killing of bacteria. Pharmacodynamic studies of fluoroquinolones

in animal infection models and in human trials indicate that the primary determinant of efficacy is the AUC

/MIC

ratio.

Mechanism of resistance

Resistance to fluoroquinolones can arise through mutations in DNA gyrase and topoisomerase IV. Other mechanisms

may include over-expression of efflux pumps, impermeability, and protein-mediated protection of DNA gyrase. Cross

resistance should be expected between moxifloxacin and other fluoroquinolones.

The activity of moxifloxacin is not affected by mechanisms of resistance that are specific to antibacterial agents of

(incl. pain in back,

chest, pelvic and

extremities)

Sweating

Infusion site

(thrombo-)

phlebitis

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other classes.

Breakpoints

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

Microbiological Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species and local information

of resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought

where the local prevalence of resistance is such that utility of the agent in at least some types of infections is

questionable.

Organism

Susceptible

Resistant

Staphylococcus spp.

0.5 mg/l

24 mm

> 1 mg/l

< 21 mm

S. pneumoniae

0.5 mg/l

22 mm

> 0.5 mg/l

< 22 mm

Streptococcus Groups A, B, C, G

0.5 mg/l

18 mm

> 1 mg/l

< 15 mm

H. influenzae

0.5 mg/l

25 mm

> 0.5 mg/l

< 25 mm

M. catarrhalis

0.5 mg/l

23 mm

> 0.5 mg/l

< 23 mm

Enterobacteriaceae

0.5 mg/l

20 mm

> 1 mg/l

< 17 mm

Non-species related breakpoints*

0.5 mg/l

> 1 mg/l

* Non-species related breakpoints have been determined mainly on the basis of

pharmacokinetic/pharmacodynamic data and are independent of MIC distributions of

specific species. They are for use only for species that have not been given a species-

specific breakpoint and are not for use with species where interpretative criteria remain

to be determined.

Commonly susceptible species

Aerobic Gram-positive micro-organisms

Staphylococcus aureus*

Streptococcus agalactiae (Group B)

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

Streptococcus pneumoniae*

Streptococcus pyogenes* (Group A)

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

S. thermophilus)

Aerobic Gram-negative micro-organisms

Acinetobacter baumanii

Haemophilus influenzae*

Legionella pneumophila

Moraxella (Branhamella) catarrhalis*

Anaerobic micro-organisms

Prevotella spp.

“Other” micro-organisms

Chlamydophila (Chlamydia) pneumoniae*

Coxiella burnetii

Mycoplasma pneumoniae*

Species for which acquired resistance may be a problem

Aerobic Gram-positive micro-organisms

Enterococcus faecalis*

Enterococcus faecium*

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5.2 Pharmacokinetic properties

Absorption and Bioavailability

After a single 400 mg intravenous 1 hour infusion peak plasma concentrations of approximately 4.1 mg/l were

observed at the end of the infusion corresponding to a mean increase of approximately 26% relative to those seen after

oral administration (3.1 mg/l). The AUC value of approximately 39 mg·h/l after i.v. administration is only slightly

higher than that observed after oral administration (35 mg·h/l) in accordance with the absolute bioavailability of

approximately 91%.

In patients, there is no need for age or gender related dose adjustment on intravenous moxifloxacin.

Pharmacokinetics are linear in the range of 50 - 1200 mg single oral dose, up to 600 mg single intravenous dose and up

to 600 mg once daily dosing over 10 days.

Distribution

Moxifloxacin is distributed to extravascular spaces rapidly. The steady-state volume of distribution (Vss) is

approximately 2 l/kg. In vitro and ex vivo experiments showed a protein binding of approximately 40 - 42%

independent of the concentration of the drug. Moxifloxacin is mainly bound to serum albumin.

Maximum concentrations of 5.4 mg/kg and 20.7 mg/l (geometric mean) were reached in bronchial mucosa and

epithelial lining fluid, respectively, 2.2 h after an oral dose. The corresponding peak concentration in alveolar

macrophages amounted to 56.7 mg/kg. In skin blister fluid concentrations of 1.75 mg/l were observed 10 h after

intravenous administration. In the interstitial fluid unbound concentration time profiles similar to those in plasma were

found with unbound peak concentrations of 1.0 mg/l (geometric mean) reached approximately 1.8 h after an

intravenous dose.

Biotransformation

Moxifloxacin undergoes Phase II biotransformation and is excreted via renal (approximately 40%) and biliary/faecal

(approximately 60%) pathways as unchanged drug as well as in the form of a sulpho-compound (M1) and a

glucuronide (M2). M1 and M2 are the only metabolites relevant in humans, both are microbiologically inactive.

In clinical Phase I and in vitro studies no metabolic pharmacokinetic interactions with other drugs undergoing Phase I

biotransformation involving cytochrome P450 enzymes were observed. There is no indication of oxidative metabolism.

Elimination

Moxifloxacin is eliminated from plasma with a mean terminal half life of approximately 12 hours. The mean apparent

total body clearance following a 400 mg dose ranges from 179 to 246 ml/min. Following a 400 mg intravenous infusion

recovery of unchanged drug from urine was approximately 22% and from faeces approximately 26%. Recovery of the

dose (unchanged drug and metabolites) totalled to approximately 98% after intravenous administration of the drug.

Aerobic Gram-negative micro-organisms

Enterobacter cloacae*

Escherichia coli*

Klebsiella oxytoca

Klebsiella pneumoniae*

Proteus mirabilis*

Anaerobic micro-organisms

Bacteroides fragilis*

Inherently resistant organisms

Aerobic Gram-negative micro-organisms

Pseudomonas aeruginosa

*Activity has been satisfactorily demonstrated in clinical studies.

Methicillin resistant S. aureus have a high probability of resistance to fluoroquinolones.

Moxifloxacin resistance rate of > 50% have been reported for methicillin resistant S. aureus.

ESBL-producing strains are commonly also resistant to fluoroquinolones.

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Renal clearance amounted to about 24 - 53 ml/min suggesting partial tubular reabsorption of the drug from the kidneys.

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

drug.

Renal impairment

The pharmacokinetic properties of moxifloxacin are not significantly different in patients with renal impairment

(including creatinine clearance > 20 ml/min/1.73 m

). As renal function decreases, concentrations of the M2 metabolite

(glucuronide) increase by up to a factor of 2.5 (with a creatinine clearance of < 30 ml/min/1.73 m

Hepatic impairment

On the basis of the pharmacokinetic studies carried out so far in patients with liver failure (Child Pugh A, B), it is not

possible to determine whether there are any differences compared with healthy volunteers. Impaired liver function was

associated with higher exposure to M1 in plasma, whereas exposure to parent drug was comparable to exposure in

healthy volunteers. There is insufficient experience in the clinical use of moxifloxacin in patients with impaired liver

function.

5.3 Preclinical safety data

In conventional repeated dose studies moxifloxacin revealed haematological and hepatic toxicity in rodents and non-

rodents. Toxic effects on the CNS were observed in monkeys. These effects occurred after the administration of high

doses of moxifloxacin or after prolonged treatment.

In dogs,

high oral

doses

60 mg/kg)

leading to plasma

concentrations

20 mg/l

caused changes

in the

electroretinogram and in isolated cases an atrophy of the retina.

After intravenous administration findings indicative of systemic toxicity were most

pronounced when moxifloxacin

was given by bolus injection (45 mg/kg) but they were not observed when moxifloxacin (40 mg/kg) was given as slow

infusion over 50 minutes.

After intra-arterial injection inflammatory changes involving the peri-arterial soft tissue were observed suggesting that

intra-arterial administration of moxifloxacin should be avoided.

Moxifloxacin was genotoxic in in vitro tests using bacteria or

mammalian cells.

In in vivo tests,

no evidence of

genotoxicity was

found despite the fact

that

very high moxifloxacin doses

were used.

Moxifloxacin was

non-

carcinogenic in an initiation-promotion study in rats.

In vitro, moxifloxacin revealed cardiac electrophysiological properties that can cause prolongation of the QT interval,

even though at high concentrations.

After intravenous administration of moxifloxacin to dogs (30 mg/kg infused over 15, 30 or 60 minutes) the degree of

QT prolongation was clearly depending on the infusion rate, i.e. the shorter the infusion time the more pronounced the

prolongation of the QT interval.

No prolongation of the QT interval was seen when a dose of 30 mg/kg was infused

over 60 minutes.

Reproductive studies performed in rats,

rabbits and monkeys indicate that

placental

transfer of moxifloxacin occurs.

Studies in rats (p.o.

and i.v.) and monkeys (p.o.) did not

show evidence of teratogenicity or impairment

of fertility

following administration of

moxifloxacin.

A slightly increased incidence of

vertebral

and rib malformations was

observed in foetuses of rabbits but only at a dose (20 mg/kg i.v.) which was associated with severe maternal toxicity.

There

an increase

in the

incidence

abortions

in monkeys

and rabbits

human therapeutic

plasma

concentrations.

Quinolones,

including moxifloxacin,

are known to cause lesions in the cartilage of the major diarthrodial

joints in

immature animals.

6 PHARMACEUTICAL PARTICULARS

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6.1 List of excipients

Sodium chloride

Hydrochloric acid 1 N (for pH-adjustment)

Sodium hydroxide solution 2 N (for pH-adjustment)

Water for injections

6.2 Incompatibilities

The following solutions are incompatible with moxifloxacin solution for infusion:

Sodium chloride 10% and 20% solutions

Sodium bicarbonate 4.2% and 8.4% solutions

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life

Polyolefine bag: 3 years

Use immediately after first opening and/or dilution.

6.4 Special precautions for storage

Do not store below 15

6.5 Nature and contents of container

Polyolefine bags with polypropylene port sealed in aluminium foil overwrap. 250 ml pack available in cartons of 5 and

12 bags.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

This product is for single use only. Any unused solution should be discarded.

The following co-infusions were found to be compatible with moxifloxacin 400 mg solution for infusion:

Water for injections, Sodium chloride 0.9%, Sodium chloride 1 molar, Glucose 5%/10%/40%, Xylitol 20%, Ringer’s

solution, Compound Sodium Lactate Solution (Hartmann’s Solution, Ringer-Lactate Solution).

Moxifloxacin solution for infusion should not be co-infused with other drugs.

Do not use if there are any visible particulate matter or if the solution is cloudy.

At cool storage temperatures precipitation may occur, which will re-dissolve at room temperature. It is therefore

recommended not to store the infusion solution below 15

7 MARKETING AUTHORISATION HOLDER

Bayer Limited

The Atrium

Blackthorn Road

Dublin 18

Ireland

8 MARKETING AUTHORISATION NUMBER

PA1410/27/002

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

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Date of first authorisation: 04 April 2003

Date of last renewal: 30 November 2013

10 DATE OF REVISION OF THE TEXT

June 2017

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