Avelox 400mg Film-coatedTablets *

"Ireland" has been added to the MAH address in Section 6.

Date of revision has been updated to October 2021 in Section 6.

2.       What you need to know before you take AveloxTalk to your doctor before taking Avelox

 

• If you have been diagnosed with leaking heart valves (heart valve regurgitation).

 

• If you have a family history of aortic aneurysm or aortic dissection or congenital heart valve disease, or other risk factors or predisposing conditions (e.g. connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Sjögren´s syndrome [an inflammatory autoimmune disease], or vascular disorders such as Takayasu arteritis, giant cell arteritis, Behcet´s disease, high blood pressure, or known atherosclerosis, rheumatoid arthritis [a disease of the joints] or endocarditis [an infection of the heart]).

When taking Avelox

• If you feel sudden, severe pain in your abdomen, chest or back, which can be symptoms of aortic aneurysm and dissection, go immediately to an emergency room. Your risk may be increased if you are being treated with systemic corticosteroids.
   
• If you start experiencing a rapid onset of shortness of breath, especially when you lie down flat in your bed, or you notice swelling of your ankles, feet or abdomen, or a new onset of heart palpitations (sensation of rapid or irregular heartbeat), you should inform a doctor immediately.

4.       Possible side effects

Cases of an enlargement and weakening of the aortic wall or a tear in the aortic wall (aneurysms and dissections), which may rupture and may be fatal, and of leaking heart valves have been reported in patients receiving fluoroquinolones (see also section 2, Warnings and precautions).

4.4    Special warnings and precautions for use

Aortic aneurysm and dissection, and heart valve regurgitation/incompetence

Epidemiologic studies report an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and of aortic and mitral valve regurgitation after intake of fluoroquinolones Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.8).

 

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 congenital heart valve disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection or heart valve disease, or in presence of other risk factors or conditions predisposing

• for both aortic aneurysm and dissection and heart valve regurgitation/incompetence (e.g. connective tissue disorders such as  Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome,  Behcet´s disease, hypertension, rheumatoid arthritis) or additionally
• for aortic aneurysm and dissection (e.g. vascular disorders such as Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren´s syndrome) or additionally
• for heart valve regurgitation/incompetence (e.g. infective endocarditis).

 

The risk of aortic aneurysm and dissection, and their rupture may also be increased in patients treated concurrently with systemic corticosteroids.

 

In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.

Patients should be advised to seek immediate medical attention in case of acute dyspnoea, new onset of heart palpitations, or development of oedema of the abdomen or lower extremities.

4.8       Undesirable effects

**Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.4).

 

 

Dysglycemia

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

Change in section 6.4  - Polypropylene/aluminium and polyvinyl chloride/polyvinylidene chloride/aluminium blisters

Change in section 6.5 - Cartons containing colourless transparent or white opaque polypropylene/aluminium blisters or colourless transparent polyvinyl chloride/polyvinylidene chloride/aluminium blisters:

 

 

 

Section 4.4 -wording in the section has changed slightly as per the below, crossed out text has been removed and bold text has been added

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 these cases of clinical manifestations of severe hypersensitivity reactions moxifloxacin should be discontinued and suitable treatment (e.g. treatment for shock) initiated.

 

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).

 

 

 

Section 4.8
Vasculitis has been added as a very rare side effect.

Avelox Tablets – 1410/27/1
www.medicines.ie

(Inserted Text; Deleted Text)

 

4.4          Special warnings and precautions for use

…

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).

…  

 

4.8          Undesirable effects

…

Metabolism and nutrition disorders

Hyperlipidemia

Hyperglycemia Hyperuricemia

Hypoglycemia

…

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.

 

 

10.          DATE OF REVISION OF THE TEXT

 

05/2014 June 2015

 

 

Section 4.8

The following text was added:

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  IMB Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax; +353 1 6762517. Website: www.imb.ie; e-mail: imbpharmacovigilance@imb.ie

Section 2:
"Each" changed to "1"

"with known effect" added after "Excipient"
"contains lactose monohydrate" updated to "contains 68mg lactose monohydrate (=66.56mg lactose)
"For a full list. . ." changed to "For the full list"

Section 3:
"Dull red tablets marked. . . ." updated to "Dull red film-coated tablet with an oblong, convex shape with facet, a dimension of 17 x 17 mm, and marked with "M400" on one side and "BAYER" on the other side.

Section 4.2:
"Dosage" changed to "Posology"
"One 400mg. . ." changed to "The recommended dose is one 400mg. . . ."
The heading "Children and adolescents" was changed to "Paediatric population"
All heading in the section were changed from underlined to italics.
The following section was added after "Duration of administration":
"Sequential (intravenous followed by oral) therapy

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

Section 4.3:
". . .listed in section 6.1." was added after the first sentence "Hypersensitivity. . ."

Section 4.4:
"(see also sections 4.3 and 4.5)." added to the statement "Medications that can reduce potassium. . ."
". . .including moxifloxacin" added after "quinolones" in the paragraph about peripheral neuropathy.
". . .self injurious behaviour. . ." replaced ". . .self endangering behaviour. . ." in the paragraph about psychiatric reactions.
". . .in samples taken from patients currently receiving moxifloxacin" added after "false negative results" in the paragraph "Interference with biological tests".

Section 4.5:
". . .(e.g. loop and thiazide-type diuretics, laxatives and enemas [high dose], corticosteroids, amphotericin B). . ." was added after ". . .medication that can reduce potassium. . ."
In the sentence "Concomitant administration of charcoal. . ." leads" was changed to "led".

 

Sequential (intravenous followed by oral) therapy

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

Section 4.6:
The main heading "Pregnancy and lactation" was updated to "Fertility, pregnancy and lactation"
The subheading "Lactation" was changed to "Breastfeeding"
The subheading:
 "Fertility
Animal studies do not indicate impairment of fertility (see section 5.3)" was added to this section.

Section 4.8:
"Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as:

-        common (³ 1/100 to < 1/10)

-        uncommon (³ 1/1,000 to < 1/100)

-        rare (³ 1/10,000 to < 1/1,000)

-        very rare (< 1/10,000)" was added before the table.

The frequencies (ie. ≥1/100 to <1/10) were removed from the table..
"MedDRA" added after "System Organ Class"

Under the "Rare" and "Very rare" columns of Psychiatric disorders, "self-endangering"was changed to "self-injurious"
Under the "Rare" column of Nervous system disorders "Peripheral neuropathy and polyneuropathy" was added.
Under the "Uncommon" column of Gastrointestinal disorders "decreased appetite and food intake" was added.

In the paragraph after the table, ". . . , peripheral neuropathy. . ." was removed after ". . .photosensitivity reaction".

Section 5.1:
"In vitro susceptibilty data" changed to "Breakpoints"
". . .and disk diffusion. . ." added after ". . MIC. . ." and the date at the end of the sentence was changed to "(01.012012)".

The first table was updated to:

Organism	Susceptible	Resistant
Staphylococcus spp.	≤ 0.5 mg/l ³ 24 mm	> 1 mg/l < 21 mm
S. pneumoniae	≤ 0.5 mg/l ³ 22 mm	> 0.5 mg/l < 22 mm
Streptococcus Groups A, B, C, G	≤ 0.5 mg/l ³ 18 mm	> 1 mg/l < 15 mm
H. influenzae	≤ 0.5 mg/l ³ 25 mm	> 0.5 mg/l < 25 mm
M. catarrhalis	≤ 0.5 mg/l ³ 23 mm	> 0.5 mg/l < 23 mm
Enterobacteriaceae	≤ 0.5 mg/l ³ 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.

The following was removed from the SPC:

 

Clinical and Laboratory Standards Institute™ (CLSI), formerly NCCLS breakpoints are presented in the below table for MIC testing (mg/l) or disc diffusion testing (zone diameter [mm]) using a 5-μg moxifloxacin disc.

 

Clinical and Laboratory Standards Institute™ (CLSI) MIC and disc diffusion breakpoints for

Staphylococcus spp. and fastidious organisms (M100-S17, 2007) and MIC breakpoints for anaerobes (M11-A7, 2007):

 

Organism	Susceptible	Intermediate	Resistant
S. pneumoniae	≤   1 mg/l   ≥   18 mm	2 mg/l 15 - 17 mm	≥   4 mg/l   ≤   14 mm
Haemophilus   spp.	≤   1 mg/l   ≥   18 mm	- -	- -
Staphylococcus   spp.	≤   0.5 mg/l   ≥   24 mm	1 mg/l 21 - 23 mm	≥   2 mg/l   ≤   20 mm
Anaerobes	≤   2 mg/l	4 mg/l	≥   8 mg/l

Theheading "microbiological susceptibility" was added above the paragraph "the prevalence of acquired. . ."
In the table:
            Under the section "Commonly susceptible species":
                    "Streptococcus viridans group  "(S.viridans, S. mutans, S. mitis, S. sanguinis, S. salivarius, S. thermophilus)" were added inder the heading "Aerobic Gram-positive micro-organisms"

                    "Acinetobacter baumanii" and "legionella pneumophila" were added and "Klebsiella pneumoniae" was removed under the heading "Aerobic Gram-negative micro-organisms"

                    "Peptostreptococcus spp." was removed from under the heading "Anaerobic micro-organisms"

                    "legionella pneumophila" removed from the heading "other micro-organisms"

            Under the sectiom "Species for which acquired resistance may be a problem":
                    "Enterococcus Faecalis" and "Enterococcus faecium" were added under the heading "Aerobic Gram-positive micro-organisms"

                    "Klebsiella pneumoniae" and "Proteus mirabilis" were added under the heading "Aerobic gram-negative micro-organisms"
    
                    The heading "Anaerobic micro-organisms" was added with "Bacteroides fragilis" and "Peptostreptococcus spp." added under it.

Section 5.2:
"Metabolism" was changed to "Biotransformation"

The font of the heading "Elderly and patients with low body weight", "Renal impairment" and "Hepatic impairment" were changed to italics.

Section 6.5:
This section was changed from:
Cartons containing colourless or white opaque polypropylene/aluminium blisters:

 

The film-coated tablets are available in packs of 5, 7, and 10 tablets.

Hospital packs containing 25 (5 x 5), 50 (5 x 10), 70 (7 x 10) film-coated tablets or bundled containing 80 (5 x 16) or 100 (10 x 10) film-coated tablets.

Aluminium/aluminium blisters, pack size one tablet in a carton.

Not all pack sizes may be marketed.

to:

 

 

Cartons containing colourless or white opaque polypropylene/aluminium blisters:

 

The film-coated tablets are available in packs of 5, 7, and 10 tablets, in hospital packs containing 25 (5 x 5), 50 (5 x 10), 70 (7 x 10) film-coated tablets or in hospital multipacks containing 80 (5 packs of 16) or 100 (10 packs of 10) film-coated tablets.

 

Cartons containing aluminium/aluminium blisters are available in packs of one film-coated tablet.

 

Not all pack sizes may be marketed.

 

 

{Deleted text; Inserted text}

 

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. In the analysis of ECGs obtained in the clinical trial program, QTc prolongation with moxifloxacin was 6 msec ± 26 msec, 1.4% compared to baseline. As women tend to have a longer baseline QTc interval compared with men, they may be more sensitive to QTc-prolonging medications. Elderly patients may also be more susceptible to drug-associated effects on the QT interval.
Medication that can reduce potassium levels should be used with caution in patients receiving moxifloxacin.
Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients), such as acute myocardial ischaemia or QT prolongation as this may lead to an increased risk for ventricular arrhythmias (incl. torsade de pointes) and cardiac arrest (see also section 4.3). The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded.
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.
If signs of cardiac arrhythmia occur during treatment with moxifloxacin, treatment should be stopped and an ECG should be performed.

 

………………………………………………

 

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 particularly 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). Tendon inflammation and rupture may occur even up to several months after discontinuing quinolone therapy including moxifloxacin.

 

…………………………………………………..

 

 

4.5          Interaction with other medicinal products and other forms of interaction

Interactions with medicinal products

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

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

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

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

-           tricyclic antidepressive agents

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

-           certain antihistaminics (terfenadine, astemizole, mizolastine)

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

 

Moxifloxacin should be used with caution in patients who are taking medication that can reduce potassium levels or medication that is associated with clinically significant bradycardia.

 

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

 

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

 

After repeated dosing in healthy volunteers, moxifloxacin increased C_max 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 antibiotics, 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 antibiotic therapy 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. Even if during an interaction study performed in healthy volunteers between moxifloxacin and warfarin, negative results have been observed, the precautionary measures as above stated should apply to warfarin as for other anticoagulants.

 

Clinical studies have shown that there are 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 support these findings this data. 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       Pregnancy and lactation

 

Pregnancy

The use of moxifloxacin during pregnancy is contraindicated. The safety of moxifloxacin in human pregnancy has not been evaluated. Reversible joint injuries are described in children receiving some quinolones, however this effect has not been reported as occurring on exposed foetuses. 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).

 

 

Lactation

The use of moxifloxacin during breast feeding is contraindicated. As with other quinolones, moxifloxacin has been shown to cause lesions in the cartilage of the weight bearing joints of immature animals. Preclinical data indicate that moxifloxacin passes into milk. 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).

 

 

The Date of Revision of the text (Section 10) has been updated to “February 2012”

Section 4.5 (Interaction with other medicinal products and other forms of interaction):  has been updated as follows:

 

BEFORE:

“Interactions with medicinal products

An additive effect on QT interval prolongation of moxifloxacin and the following drugs cannot be excluded: antiarrhythmics class IA (e.g. quinidine, hydroquinidine, disopyramide) or antiarrhythmics class III (e.g. amiodarone, sotalol, dofetilide, ibutilide), neuroleptics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressive agents, certain antimicrobials (sparfloxacin, erythromycin IV, pentamidine, antimalarials particularly halofantrine), certain antihistaminics (terfenadine, astemizole, mizolastine), others (cisapride, vincamine IV, bepridil, diphemanil). This effect might lead to an increased risk of ventricular arrhythmias, notably torsade de pointes. Therefore moxifloxacin is contraindicated in patients treated with these drugs (see also section 4.3).”

 

AFTER

“Interactions with medicinal products

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

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

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

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

-        tricyclic antidepressive agents

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

-        certain antihistaminics (terfenadine, astemizole, mizolastine)

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

Section 4.9 (overdose): has been updated as follows:

 

BEFORE:

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

 

AFTER:

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

 

 

In Section 10, the date of revision of the text has been changed from “March 2011” to “July 2011”.

DE/H/0155/002/II/059

IMB ref. C2086436

 

Deleted text: text with strikethrough

 

 

4.4     Special warnings and precautions for use

 

Patients with special cSSSI

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

 

 

10.     DATE OF REVISION OF THE TEXT

 

Changed to:

 

March 2011

DE/H/0155/001/II/060

IMB ref: C2086437

 

4.4     Special warnings and precautions for use

 

Insertion of subsection:

 

Patients with special cSSSI

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

 

 

10.     DATE OF REVISION OF THE TEXT

 

Changed to:

 

March 2011

4.4     Special warnings and precautions for use

 

Superceded text

Newly approved text

-        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 these cases moxifloxacin should be discontinued and suitable treatment (e.g. treatment for shock) initiated. -        Moxifloxacin has been shown to prolong the QTc interval on the electrocardiogram in some patients. In the analysis of ECGs obtained in the clinical trial program, QTc prolongation with moxifloxacin was 6 msec ± 26 msec, 1.4% compared to baseline. As women tend to have a longer baseline QTc interval compared with men, they may be more sensitive to QTc-prolonging medications. Elderly patients may also be more susceptible to drug-associated effects on the QT interval. Medication that can reduce potassium levels should be used with caution in patients receiving moxifloxacin. Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients), such as acute myocardial ischaemia or QT prolongation as this may lead to an increased risk for ventricular arrhythmias (incl. torsade de pointes) and cardiac arrest (see also section 4.3). The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded. 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. If signs of cardiac arrhythmia occur during treatment with moxifloxacin, treatment should be stopped and an ECG should be performed. -        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. -        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. -        Quinolones are known to trigger seizures. Use should be with caution in patients with CNS disorders which may predispose to seizures or lower the seizure threshold. -        Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoaesthesias, dysaesthesias, or weakness have been reported in patients receiving quinolones. 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 (see section 4.8). -        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. -        Moxifloxacin should be used with caution in patients with myasthenia gravis because the symptoms can be exacerbated. -        Tendon inflammation and rupture may occur with quinolone therapy including moxifloxacin, particularly in elderly patients and in those treated concurrently with corticosteroids. At the first sign of pain or inflammation, patients should discontinue treatment with moxifloxacin and rest the affected limb(s). -        Elderly patients with renal disorders should use moxifloxacin with caution if they are unable to maintain adequate fluid intake, because dehydration may increase the risk of renal failure. -        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). -        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 a family history of, or actual glucose-6-phosphate dehydrogenase deficiency are prone to haemolytic reactions when treated with quinolones. Therefore, moxifloxacin should be used with caution in these patients. -        Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. -        For patients with complicated pelvic inflammatory disease (e.g. associated with a tubo-ovarian or pelvic abscess), for whom an intravenous treatment is considered necessary, treatment with Avelox 400 mg film-coated tablets is not recommended. -        Pelvic inflammatory disease may be caused by fluoroquinolone resistant Neisseria gonorrhoeae. Therefore in such cases empirical moxifloxacin should be co-administered with another appropriate antibiotic (e.g. a cephalosporin) unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded. If clinical improvement is not achieved after 3 days of treatment, the therapy should be reconsidered. -        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). -        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).

Prolongation of QTc interval and potentially QTc-prolongation-related clinical conditions Moxifloxacin has been shown to prolong the QTc interval on the electrocardiogram in some patients. In the analysis of ECGs obtained in the clinical trial program, QTc prolongation with moxifloxacin was 6 msec ± 26 msec, 1.4% compared to baseline. As women tend to have a longer baseline QTc interval compared with men, they may be more sensitive to QTc-prolonging medications. Elderly patients may also be more susceptible to drug-associated effects on the QT interval. Medication that can reduce potassium levels should be used with caution in patients receiving moxifloxacin. Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients), such as acute myocardial ischaemia or QT prolongation as this may lead to an increased risk for ventricular arrhythmias (incl. torsade de pointes) and cardiac arrest (see also section 4.3). The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded. 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. If signs of cardiac arrhythmia occur during treatment with moxifloxacin, treatment should be stopped and an ECG should be performed.   Hypersensitivity / allergic reactions Hypersensitivity and allergic reactions have been reported for fluoroquinolones including moxifloxacin after first administration. Anaphylactic reactions can progress to a life-threatening shock, even after the first administration. In these cases moxifloxacin should be discontinued and suitable treatment (e.g. treatment for shock) initiated.   Severe liver disorders Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with moxifloxacin (see section 4.8). Patients should be advised to contact their doctor prior to continuing treatment if signs and symptoms of fulminant hepatic disease develop such as rapidly developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy. Liver function tests/investigations should be performed in cases where indications of liver dysfunction occur.   Serious bullous skin reactions Cases of bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with moxifloxacin (see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.   Patients predisposed to seizures Quinolones are known to trigger seizures. Use should be with caution in patients with CNS disorders or in the presence of other risk factors which may predispose to seizures or lower the seizure threshold. In case of seizures, treatment with moxifloxacin should be discontinued and appropriate measures instituted.   Peripheral neuropathy Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoaesthesias, dysaesthesias, or weakness have been reported in patients receiving quinolones. 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 (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-endangering 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 may occur with quinolone therapy including moxifloxacin, particularly 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. Tendon inflammation and rupture may occur even up to several months after discontinuing quinolone therapy including moxifloxacin.   Patients with renal impairment Elderly patients with renal disorders should use moxifloxacin with caution if they are unable to maintain adequate fluid intake, because dehydration may increase the risk of renal failure.   Vision disorders If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately (see sections 4.7 and 4.8).   Prevention of photosensitivity reactions Quinolones have been shown to cause photosensitivity reactions in patients. However, studies have shown that moxifloxacin has a lower risk to induce photosensitivity. Nevertheless patients should be advised to avoid exposure to either UV irradiation or extensive and/or strong sunlight during treatment with moxifloxacin.   Patients with glucose-6-phosphate dehydrogenase deficiency Patients with a family history of, or actual glucose-6-phosphate dehydrogenase deficiency are prone to haemolytic reactions when treated with quinolones. Therefore, moxifloxacin should be used with caution in these patients.   Patients with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.   Patients with pelvic inflammatory disease For patients with complicated pelvic inflammatory disease (e.g. associated with a tubo-ovarian or pelvic abscess), for whom an intravenous treatment is considered necessary, treatment with Avelox 400 mg film-coated tablets is not recommended. Pelvic inflammatory disease may be caused by fluoroquinolone-resistant Neisseria gonorrhoeae. Therefore in such cases empirical moxifloxacin should be co-administered with another appropriate antibiotic (e.g. a cephalosporin) unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded. If clinical improvement is not achieved after 3 days of treatment, the therapy should be reconsidered.   Interference with biological tests Moxifloxacin therapy may interfere with the Mycobacterium spp. culture test by suppression of mycobacterial growth causing false negative results.   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

The following sentences in section 4.5 have been updated:

 

An additive effect on QT interval prolongation between of moxifloxacin and the following drugs cannot be excluded: antiarrhythmics class IA (e.g. quinidine, hydroquinidine, disopyramide) or antiarrhythmics class III (e.g. amiodarone, sotalol, dofetilide, ibutilide), neuroleptics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressive agents, certain antimicrobials (sparfloxacin, erythromycin IV, pentamidine, antimalarials particularly halofantrine), certain antihistaminics (terfenadine, astemizole, mizolastine), others (cisapride, vincamine IV, bepridil, diphemanil). This effect might lead to an increased risk of ventricular arrhythmias, notably torsade de pointes.

 

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

 

4.8       Undesirable effects

The following changes have been made to the ADR table

Psychiatric Disorders		Anxiety reactions Psychomotor hyperactivity / agitation	Emotional lability Depression (in very rare cases potentially culminating in self-endangering behaviour, such as suicidal ideations/ thoughts, or suicide attempts, see section 4.4) Hallucination	Depersonalization Psychotic reactions (potentially culminating in self-endangering behaviour, such as suicidal ideations/ thoughts, or suicide attempts, see section 4.4)
Vascular Disorders		Vasodilatation	Hypertension Hypotension
Cardiac and Vascular Disorders	QT prolongation in patients with hypokalaemia (see sections 4.3 and 4.4)	QT prolongation (see section 4.4) Palpitations Tachycardia Atrial fibrillation Angina pectoris Vasodilation	Ventricular tachyarrhythmias Syncope (i.e., acute and short lasting loss of consciousness) Hypertension Hypotension	Unspecified arrhythmias Torsade de Pointes (see section 4.4) Cardiac arrest (see section 4.4)
Musculoskeletal, Connective Tissue and Bone 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)

 

 

4.9     Overdose

 

Insertion of the sentence: “ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.”

 

 

5.       PHARMACOLOGICAL PROPERTIES

 

5.1     Pharmacodynamic properties

 

Deletion of subsection:

 

Interference with culture test

Moxifloxacin therapy may give false negative culture results for Mycobacterium spp. by suppression of mycobacterial growth.

 

10.     DATE OF REVISION OF THE TEXT

 

Insertion of “February 2011”

4.       Clinical particulars

 

4.1     Therapeutic indications

 

Old text

Updated text

Avelox 400 mg film-coated tablets are indicated for the treatment of the following bacterial infections in patients of 18 years and older (see section 4.4, 4.8 and 5.1):   -        Acute bacterial sinusitis (ABS) -        Acute exacerbations of chronic bronchitis (AECB) Moxifloxacin should be used to treat adequately diagnosed ABS and AECB only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of these infections or when these have failed to resolve the infection.   -        Community acquired pneumonia, except severe cases Moxifloxacin should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection.   -        Mild to moderate pelvic inflammatory disease (i.e. infections of female upper genital tract, including salpingitis and endometritis), without an associated tubo-ovarian or pelvic abscess. Avelox 400 mg film-coated tablets are not recommended for use in monotherapy of mild to moderate pelvic inflammatory disease but should be given in combination with another appropriate antibacterial agent (e.g. a cephalosporin) due to increasing moxifloxacin resistance of Neisseria gonorrhoeae unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded (see sections 4.4 and 5.1).   Avelox 400 mg film-coated tablets are indicated for the treatment of the above infections if they are caused by bacteria susceptible to moxifloxacin.   Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Avelox 400 mg film-coated tablets are indicated for the treatment of the following bacterial infections in patients of 18 years and older caused by bacteria susceptible to moxifloxacin (see sections 4.4, 4.8 and 5.1). Moxifloxacin should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of these infections or when these have failed:   -        Acute bacterial sinusitis (adequately diagnosed) -        Acute exacerbations of chronic bronchitis (adequately diagnosed) -        Community acquired pneumonia, except severe cases -        Mild to moderate pelvic inflammatory disease (i.e. infections of female upper genital tract, including salpingitis and endometritis), without an associated tubo-ovarian or pelvic abscess. Avelox 400 mg film-coated tablets are not recommended for use in monotherapy of mild to moderate pelvic inflammatory disease but should be given in combination with another appropriate antibacterial agent (e.g. a cephalosporin) due to increasing moxifloxacin resistance of Neisseria gonorrhoeae unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded (see sections 4.4 and 5.1).   Avelox 400 mg film-coated tablets may also be used to complete a course of therapy in patients who have shown improvement during initial treatment with intravenous moxifloxacin for the following indications: - Community-acquired pneumonia - Complicated skin and skin structure infections Avelox 400 mg film-coated tablets should not be used to initiate therapy for any type of skin and skin structure infection or in severe community-acquired pneumonia.   Consideration should be given to official guidance on the appropriate use of antibacterial agents.

 

 

10.     DATE OF REVISION OF THE TEXT

Changed to “November 2010”

 



Renewal, Lego, Art 107 & PID referral update June 2010:

 

Section 4.1 changed to:

 

“Avelox 400 mg film-coated tablets are indicated for the treatment of the following bacterial infections in patients of 18 years and older (see section 4.4, 4.8 and 5.1):

 

-           Acute bacterial sinusitis (ABS)

-           Acute exacerbations of chronic bronchitis (AECB)

Moxifloxacin should be used to treat adequately diagnosed ABS and AECB only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of these infections or when these have failed to resolve the infection.

 

-           Community acquired pneumonia, except severe cases

Moxifloxacin should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection.

 

-        Mild to moderate pelvic inflammatory disease (i.e. infections of female upper genital tract, including salpingitis and endometritis), without an associated tubo-ovarian or pelvic abscess.
Avelox 400 mg film-coated tablets are not recommended for use in monotherapy of mild to moderate pelvic inflammatory disease but should be given in combination with another appropriate antibacterial agent (e.g. a cephalosporin) due to increasing moxifloxacin resistance of Neisseria gonorrhoeae unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded (see sections 4.4 and 5.1).

 

Avelox 400 mg film-coated tablets are indicated for the treatment of the above infections if they are caused by bacteria susceptible to moxifloxacin.

 

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

 

Section 4.2

 

Subsection “children and adolescents”: “Moxifloxacin is contraindicated in children and growing adolescents.” changed to “Moxifloxacin is contraindicated in children and adolescents (< 18 years).”

 

Subsection “Duration of administration”, addition of the following:

“-Acute bacterial sinusitis          7 days

-Mild to moderate pelvic inflammatory disease  14 days”

 

Section 4.3

 

“Children and growing adolescents.” changed to “Patients below 18 years of age.”

 

Addition of the following to section 4.4:

 

Where small sections of text are added to a long sentence, the additional text is highlighted in green, a stikethrough the text indicates deletion.

 

“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.”

 

“Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions (especially women and elderly patients), such as acute myocardial ischaemia or QT prolongation as this may lead to an increased risk for ventricular arrhythmias (incl. torsade de pointes) and cardiac arrest (see also section 4.3)”

Cases of fulminant hepatitis potentially leading to life-threatening liver failure (including fatal cases) have been reported with moxifloxacin (see section 4.8).

 

“Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoaesthesias, dysaesthesias, or weakness have been reported in patients receiving quinolones. 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 (see section 4.8).”

 

Information on diarrhoea changed from:

“Antibiotic associated colitis (incl. pseudomembranous colitis) has been reported in association with the use of broad spectrum antibiotics including moxifloxacin; therefore it is important to consider this diagnosis in patients who develop serious diarrhoea during or after the use of moxifloxacin. In this situation adequate therapeutic measures should be initiated immediately. Drugs inhibiting peristalsis are contraindicated in this situation.”

to

“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.”

 

Addition of:

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

 

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

 

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

 

“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).”

 

“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).”

 

Section 4.7

Addition of the following text highlighted in green:

 

 “However, fluoroquinolones including moxifloxacin may result in an impairment of the patient's ability to drive or operate machinery due to CNS reactions (e.g. dizziness; acute, transient loss of vision, see section 4.8) or acute and short lasting loss of consciousness (syncope, see section 4.8).”

 

Section 4.8

 

Classification of very rare events changed from: “≤10,000” to “<10,000”

 

Addition of “Agranulocytosis” as a very rare adverse event observed.

 

In psychiatric disorders addition of “suicidal ideations/ thoughts, or suicide attempts” as example of self endangering behaviour under the category rare and very rare adverse event observed.

 

Under eye disorders addition of “Transient loss of vision (especially in the course of CNS reactions, see sections 4.4 and 4.7)” as a very rarely observed adverse event.

 

Under ear and labyrinth disorders insertion of “Hearing impairment incl. deafness (usually reversible)” as a rarely observed adverse event.

 

Addition of “haemolytic anaemia” and “peripheral neuropathy” as side effects reported with other fluoroquinolones. Deletion of “transient loss of vision” from this sentence.

 

Addition of explanation for the event “syncope”: “(i.e., acute and short lasting loss of consciousness)”

Under “Hepatobiliary disorders” addition of the text highlighted in green:

“Fulminant hepatitis potentially leading to life-threatening liver failure (incl. fatal cases, see section 4.4)”

 

Addition of “Exacerbation of symptoms of myasthenia gravis (see section 4.4)” as a very rare side effect.

 

“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: trasnient loss of vision, hypernatraemia, hypercalcaemia, haemolysis, haemolytic anaemia, rhabdomyolysis, photosensitivity reactions, peripheral neuropathy (see section 4.4).”

 

Section 5.1

 

Addition of the following to the commonly susceptible species table:

“Gardnerella vaginalis

Chlamydia trachomatis

Mycoplasma genitalium

Mycoplasma hominis”

 

Addition of the following to the spceies for which acquired resistance might be a problem table:

“Neisseria gonorrhoeae”

 

Addition of the following text highlighted in green:

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

 

 

 

Section 6.4

“Store in the original pack” changed to “Store in the original package in order to protect from moisture.” for Polypropylene/aluminium blisters and Aluminium/aluminium blisters.

 

Section 7

“Bayer Healthcare AG” changed to “Bayer Schering Pharma AG”

 

Section 9

 

Change of the date of last renewal to: “30^th November 2008”

 

Section 10

Changed to “May 2010”

Section 4.4:

 Cases of fulminant hepatitis potentially leading to life-threatening liver failure 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.

 

'Pseudomembranous colitis has been reported in association with the use of broad spectrum antibiotics including moxifloxacin' has been replaced with the following text:

Antibiotic associated colitis (incl. pseudomembranous colitis) has been reported in association with the use of broad spectrum antibiotics including moxifloxacin.

 

Section 4.8:

 Headers and text updated to read as follows:

 

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

 

Blood and Lymphatic System Disorders

Anaemia Leucopenia(s) Neutropenia Thrombocytopenia Thrombocythemia Blood eosinophilia Prothrombin time prolonged / INR increased

Prothrombin level increased / INR decreased

 

Psychiatric Disorders

Anxiety reactions Psychomotor hyperactivity / agitation

Emotional lability Depression (in very rare cases potentially culminating in self-endangering behaviour) Hallucination

Depersonalization Psychotic reactions (potentially culminating in self-endangering behaviour)

 

Cardiac and Vascular Disorders

QT prolongation in patients with hypokalaemia (see section 4.4)

QT prolongation (see section 4.4) Palpitations Tachycardia Atrial fibrillation Angina pectoris Vasodilatation

Ventricular tachyarrhythmias Syncope Hypertension Hypotension

Unspecified arrhythmias Torsade de Pointes (see section 4.4) Cardiac arrest (see section 4.4)

 

Gastrointestinal Disorders

Nausea Vomiting Gastrointestinal and abdominal pains Diarrhoea

Anorexia Constipation Dyspepsia Flatulence Gastritis Increased amylase

Dysphagia Stomatitis Antibiotic associated colitis (incl. pseudomembranous 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 (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)

 

General Disorders and Administration Site Conditions

Injection and infusion site reactions

Feeling unwell (predominantly asthenia or fatigue) Painful conditions (incl. pain in back, chest, pelvic and extremities) Sweating Infusion site (thrombo-) phlebitis

Oedema

 

Uncommon:          Ventricular tachyarrhythmias, hypotension, oedema, antibiotic associated colitis (incl. pseudomembranous colitis, in very rare cases associated with life-threatening complications, see section 4.4).

 

 

In vitro Susceptibility Data

Clinical and Laboratory Standards Institute¢â (CLSI) MIC and disc diffusion breakpoints for Staphylococcus spp. and fastidious organisms (M100-S17, 2007) and MIC breakpoints for anaerobes (M11-A7, 2007). (Aerobes M100-S16,2006 has been deleted).

 

Species for which acquired resistance may be a problem

Aerobic Gram-positive micro-organisms

Enterococcus faecalis*

Staphylococcus aureus (methicillin-resistant)⁺

Aerobic Gram-negative micro-organisms

Enterobacter cloacae

Escherichia coli*

Klebsiella oxytoca

 

Section 7

MA holder is now Bayer Limited, The Atrium, Blackthorn Avenue, Dublin 18.

 

 

Section 4.4 (Special warnings and precautions for use:

Bullet point 2, paragraph 3 has been re-worded.

Bullet point 9, has been reworded.

Bullet point 10, has been reworded

 

Section 4.5 (Interaction with other medicinal products and other forms of interactions):

Paragraph 7 has been amended to read: “Clinical studies have shown that there are no interactions following …..”. 

 

Section 4.7 (Effects on ability to drive and use machines):

The wording has been amended slightly: “….. (e.g. dizziness, see section 4.8). 

 

Section 4.8 (Undesirable effects):

The table has been extensively revised to reflect MedDRA terminology.

 

Section 5.1 (Pharmacodynamic properties):

The wording has been updated in line with the Company Core Data Sheet.

 

Section 10 (Date of revision of the text):

This has been updated to ’26.07.2006’.