When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
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
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)
Section 4.9 (overdose): has been updated as follows:
“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
Insertion of subsection:
Clinical efficacy of intravenous moxifloxacin in the treatment of severe burn infections, fasciitis and diabetic foot infections with osteomyelitis has not been established.
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)
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.
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)
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.
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):
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”
“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: “30th 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
Depression (in very rare cases potentially culminating in self-endangering behaviour)
Psychotic reactions (potentially culminating in self-endangering behaviour)
QT prolongation in patients with hypokalaemia (see section 4.4)
Syncope
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
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’.