Download Moxifloxacin "Orion"

VI.2 Elements for a Public Summary
VI.2.1 Overview of disease epidemiology
Moxifloxacin is a broad spectrum antibiotic indicated for the treatment of a variety of bacterial
infections such as acute exacerbation of chronic bronchitis, acute bacterial sinusitis, community
acquired pneumonia, complicated skin and skin-structure infections, and pelvic inflammatory disease.
Acute exacerbation of chronic bronchitis
Chronic bronchitis is a condition where there is a prolonged inflammation in the upper part of the
respiratory tract with a mucus producing cough most days of the month. An acute exacerbation
describes a condition with sudden worsening of the inflammation. Chronic bronchitis occurs in 3-17%
of the population in most developed countries and can be fatal if not treated.
Acute bacterial sinusitis
Acute sinusitis (acute rhinosinusitis) causes the cavities around the nasal passages (sinuses) to
become inflamed and swollen. This interferes with drainage and causes mucus to build up. With acute
sinusitis, it may be difficult to breathe through the nose. The area around the eyes and face may feel
swollen, and the patient may have throbbing facial pain or a headache.
Acute sinusitis is most often caused by the common cold. Other triggers include allergies, bacterial and
fungal infections. Acute bacterial sinusitis has been reported to complicate up to 2% of common colds
and influenza-like illnesses in adults and up to 10% of such cases in children. It can lead to serious
complications, if untreated or undertreated; Furthermore, acute bacterial sinusitis can evolve into
chronic sinusitis, which leads to significant illness.
Community-acquired pneumonia
Community-acquired pneumonia (CAP) is defined as an inflammation of the lungs that has not been
acquired in a hospital or long-term care institution. CAP is an acute condition. Depending on the
country and populations studied, CAP may affect 1.6 to 11.6 out of 1000 persons in a given year.
Patients over 60 years have a higher risk to develop CAP. The incidence of CAP peaks in the winter
season. Up to 61% of patients with CAP are admitted to hospital. The reported death rates of adults
admitted to hospital with CAP vary from 6% to 14%. The mortality of patients with severe CAP
requiring admission to an Intensive Care Unit is high, varying from 22% to over 50%.
Complicated skin and skin-structure infections
Complicated skin and skin structure infections (cSSSIs) are the most common type of bacterial
infection, and can range in severity from mild inflammation to extensive tissue destruction with lifethreatening spread of infections inside the body (sepsis). The exact frequency of cSSSIs is unknown.
cSSSIs that have been classified as complicated include infected skin ulcers caused by poor blood
supply (ischemic ulcers), diabetic foot infections, major abscesses, human or animal bite wound
infections, infections involving deeper soft tissues such as surgical or post-traumatic wound infections,
and infection of the dead deep layer of the skin (necrotizing fasciitis). Untreated cSSSIs may spread
and cause major tissue destruction, bone morrow infection, diabetic foot infection, local amputation or
even limb loss and death.
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Pelvic inflammatory disease
Pelvic inflammatory disease (PID) is an infection of the female upper genital tract and one of the most
common causes of illness among women of childbearing age. It causes acute pain and discomfort and,
in many women, leads to long-term problems such as chronic pain, infertility or outside the normal site
(ectopic) pregnancy, in addition to its considerable economic cost and psychological stress. The
frequency of PID peaks in the age group of 18 to 29 with 88.7 PID hospitalizations per 10,000. More
than 90% of hospitalizations for PID occur in 18 to 49-year-old women. The death rate for noncomplicated PID is very low.
Women with clinically apparent PID are at risk of damage to oviducts (uterine tubes) and subsequent
adverse reproductive complications, with PID caused by Chlamydia infection being identified as the
most important preventable cause of infertility and adverse pregnancy outcome.
VI.2.2 Summary of treatment benefits
Pathogenic bacterial infections may lead to complications, suffering and in serious cases even death.
Therefore appropriate and effective treatment is important.
The active ingredient of this medicinal product, moxifloxacin, belongs to a group of antibiotics called
fluoroquinolones. It works by killing bacteria that cause infections.
Moxifloxacin is used in patients aged 18 years and above for treating bacterial infections caused by
bacteria against which moxifloxacin is active. It should only be used to treat these infections when
usual antibiotics cannot be used or have not worked. Sometimes it is necessary to combine other
antibiotic to the treatment.
VI.2.3 Unknowns relating to treatment benefits
Efficacy and safety have not been established in children and adolescents under 18 years of age.
VI.2.4 Summary of safety concerns
Important identified risks
Risk
What is known
Preventability
Hypersensitivity, anaphylaxis
Hypersensitivity and allergic
Patients who are allergic to the
(serious allergic reaction)
reactions have been reported for
active substance moxifloxacin,
fluoroquinolones including
any other quinolone antibiotics
moxifloxacin even after first
or any of the other ingredients
administration.
of this medicine must not take
Moxifloxacin Orion.
Anaphylactic reactions can
progress to a life-threatening
If allergic reactions to
shock, even after the first
moxifloxacin appear, doctor
administration. Symptoms
needs to be contacted,
include tightness in the chest,
treatment should be
feeling dizzy, feeling sick or
discontinued and suitable
faint, or dizziness when standing
treatment (e.g. treatment for
up.
shock) initiated. In case of
anaphylactic reactions
immediate medical help is
necessary.
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Risk
What is known
Preventability
Abnormal heart rhythm
Moxifloxacin can cause
Patients who were born with or
(Prolongation of QTc interval)
potentially life-threatening
have had any condition with
changes on the ECG, that is a
abnormal heart rhythm (seen on
prolongation of the QT-interval
ECG, electrical recording of the
i.e. delayed conduction of
heart), have salt imbalance in
electrical signals, especially in
the blood (especially low level of
female or elderly patients.
potassium or magnesium in the
blood), have a very slow heart
The risk of heart problems may
rhythm (called ‘bradycardia’),
increase with increase of the
have a weak heart (heart
dose (oral and intravenous
failure), have a history of
administration) and the speed of
abnormal heart rhythm, or
the perfusion into vein
patients who are taking other
(intravenous administration).
medicines that result in
abnormal ECG changes must not
take Moxifloxacin Orion.
Patients who are currently
taking any medicine that
decrease their blood potassium
levels must consult doctor
before taking Moxifloxacin Orion.
If patient experiences
palpitations or irregular heart
beat during the period of
treatment, patient should inform
doctor immediately. Doctor may
perform an ECG to measure
patient’s heart rhythm.
Recommended dosage and
method of administration should
be followed.
Seizure (convulsion)
Quinolone antibiotics such as
Patients who suffer from
moxifloxacin are known to
epilepsy or a condition which
trigger seizures.
makes patient likely to have
convulsions should talk to doctor
before taking Moxifloxacin Orion.
If convulsions appear, patient
should stop taking Moxifloxacin
Orion and contact doctor
immediately.
Peripheral neuronal disease
Cases of sensory or
Patients under treatment with
(nerve disorders in hands and
sensorimotor polyneuropathy
moxifloxacin should be advised
feet)
(disorders in several nerves)
to inform their doctor prior to
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Risk
What is known
Preventability
have been reported in patients
continuing treatment if
receiving quinolones including
symptoms of neuropathy such
moxifloxacin.
as pain. burning, tingling,
numbness, or weakness
develop.
Tendinopathy (tendon disorders)
Tendon inflammation and
Patients with a history of tendon
rupture (especially Achilles
disease/disorder related to
tendon), sometimes in both
quinolone treatment must not
sides, may occur with quinolone
take Moxifloxacin Orion
therapy including moxifloxacin,
Liver toxicity
even within 48 hours of starting
At the first sign of pain or
treatment and have been
inflammation, patients should
reported up to several months
discontinue treatment with
after discontinuation of therapy.
moxifloxacin, rest the affected
The risk of tendinitis and tendon
limb(s) and consult their doctor
rupture is increased in elderly
immediately in order to initiate
patients and in those treated
appropriate treatment (e.g.
concurrently with
immobilisation) for the affected
corticosteroids.
tendon.
Cases of sudden liver
Moxifloxacin Orion must not be
inflammation with strong
used in patients with impaired
symptoms potentially leading to
liver function and in patients
liver failure (including cases
with significantly increased liver
resulting to death) have been
enzyme levels.
reported with moxifloxacin.
Patients should contact their
doctor prior to continuing
treatment if signs and
symptoms of sudden liver
disease with strong symptoms
develop such as rapidly
developing weakness associated
with jaundice (yellowness of skin
and whites of the eyes), dark
urine, bleeding tendency or
hepatic encephalopathy(a
condition that causes temporary
worsening of brain function in
people with advanced liver
disease).
Liver function
tests/investigations should be
performed in cases where
indications of liver dysfunction
occur.
Antibiotic associated diarrhoea
Antibiotic-associated diarrhoea
If diarrhoea becomes severe or
(including bowel inflammation)
and bowel inflammation,
persistent or if stool contains
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Risk
What is known
Preventability
in hospital setting
including serious conditions
blood or mucus patient should
called pseudomembranous
stop taking moxifloxacin
colitis and Clostridium difficile-
immediately and consult doctor.
associated diarrhoea, have been
Medicines that stop or slow
reported in association with the
down bowel movement must not
use of broad spectrum
be used.
antibiotics including moxifloxacin
and may range in severity from
mild diarrhoea to life
threatening colitis. Diarrhoea
may develop whilst or after
taking antibiotics including
moxifloxacin
Kidney failure
Kidney impairment and kidney
Older patients with kidney
failure may appear.
disorders should use
moxifloxacin with caution if they
are unable to drink enough
fluids, because dehydration may
increase the risk of kidney
failure.
Serious vision disorders
Visual disturbances including
If vision becomes impaired or
double vision, blurred vision and
any effects on the eyes are
transient loss of vision
experienced, an eye specialist
(especially in association with
should be consulted
neurological disorders) have
immediately.
been reported with
fluoroquinolones including
moxifloxacin. Fluoroquinolones
including moxifloxacin may
result in an impairment of the
patient's ability to drive or
operate machinery due to e.g.
acute, transient loss of vision.
Serious blistering / peeling of
Cases of potentially life-
Patients should be advised to
the skin and/or mucosa
threatening blistering/peeling
contact their doctor immediately
skin reactions like Stevens-
prior to continuing treatment if
Johnson syndrome or toxic
skin and/or mucosal reactions
epidermal necrolysis have been
occur.
reported with moxifloxacin.
Depression, suicidality and
Psychiatric reaction/mental
If symptoms of mental health
psychosis
health disorders may occur even
problems appear, doctor should
after the first administration of
be contacted immediately,
quinolones, including
moxifloxacin should be
moxifloxacin.
discontinued and appropriate
measures instituted.
In very rare cases depression or
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Risk
What is known
Preventability
psychotic reactions have
Caution is recommended if
progressed to suicidal thoughts
moxifloxacin is to be used in
and self-endangering behaviour
psychotic patients or in patients
such as suicide attempts.
with history of psychiatric
disease.
Worsening of myasthenia gravis
Moxifloxacin should be used with
Doctor should be informed
(abnormal muscle fatigue
caution in patients with
before starting the treatment, if
leading to weakness and in
myasthenia gravis because the
the patient has diagnosis of
serious cases paralysis)
symptoms can get worse.
myasthenia gravis.
Important potential risks
What is known (Including reason why it is considered a
Risk
potential risk)
Slower than normal heart
Bradycardia can be a serious problem if the heart doesn't pump
rhythm (bradycardia)
enough oxygen-rich blood to the body. For some people, however,
bradycardia doesn't cause symptoms or complications.
Patients with clinically relevant bradycardia must not use
Moxifloxacin Orion.
Moxifloxacin should be used with caution in patients who are taking
medications associated with clinically significant bradycardia.
Breakdown of muscle tissue
(rhabdomyolysis), muscle
Rhabdomyolysis is the breakdown of muscle tissue that leads to the
inflammation (myositis) and
release of muscle fibre contents into the blood. These substances
muscle disease (myopathy) and
are harmful to the kidney and often cause kidney damage.
muscle rupture
There have been very rare cases of rhabdomyolysis reported
following treatment with other fluoroquinolones and it might
possibly also occur during treatment with moxifloxacin.
Myositis is inflammation of the muscles that are used to move the
body. An injury, infection, or autoimmune disease can cause it.
Myositis may cause e.g. muscle weakness.
Myopathies are neuromuscular disorders in which the primary
symptom is muscle weakness due to dysfunction of muscle fibre.
Other symptoms of myopathy can include muscle cramps, stiffness,
and spasm.
When a muscle is pulled too far, one or more fibers inside the
muscle will rupture. This is called a pulled muscle, a strained
muscle or a torn muscle. A case where the muscle is torn apart
totally is called a muscle rupture.
Muscle ache, muscle cramp, muscle twitching, muscle weakness
and muscle rigidity may appear during moxifloxacin therapy.
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What is known (Including reason why it is considered a
Risk
potential risk)
Ligament rupture
Ligaments are tissues that connect bones to joints. Fluoroquinolone
antibiotics such as moxifloxacin may interfere with body’s collagen
synthesis and thus cause problems in connective tissues, including
ligaments.
Retinal detachment
Retinal detachment is an emergency situation in which a critical
layer of tissue (the retina) at the back of the eye pulls away from
the layer of blood vessels that provides it with oxygen and
nourishment. Untreated retinal detachment can lead to permanent
loss of vision. If patient’s eyesight becomes impaired or eyes seem
to be otherwise affected, an eye specialist needs to be contacted
immediately.
The association between fluoroquinolone antibiotic (such as
moxifloxacin) intake and occurrence of retinal detachment has been
investigated in several epidemiological studies using various
designs and data sources. Causal relationship between
fluoroquinolone intake and retinal detachment can neither be
established nor firmly excluded based on the available data.
Selection of drug resistant
Superinfections due to resistant bacteria or fungi may appear
isolates
during or after the moxifloxacin treatment.
Consideration should be given to official guidance on the
appropriate use of antibacterial agents. Moxifloxacin should only be
used to treat infections when usual antibiotics cannot be used or
have not worked.
Missing information
Risk
What is known
Use of moxifloxacin in children
and growing adolescents,
Due to adverse effects of moxifloxacin on the cartilage in juvenile
animals, moxifloxacin must not be used in children and adolescents
<18 years.
Joint disorder (in children and
Quinolone antibiotics are known to cause lesions in the cartilage of
adolescents)
the major diarthrodial joints in immature animals. The lowest oral
dose of moxifloxacin causing joint toxicity in juvenile dogs was four
times the maximum recommended therapeutic dose of 400 mg
(assuming a 50 kg bodyweight) on a mg/kg basis, with plasma
concentrations two to three times higher than those at the
maximum therapeutic dose.
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VI.2.5 Summary of risk minimisation measures by safety concern
All medicines have a Summary of Product Characteristics (SmPC) which provides physicians,
pharmacists and other health care professionals with details on how to use the medicine, the risks and
recommendations for minimising them.
An abbreviated version of this in lay language is provided in
the form of the package leaflet (PL). The measures in these documents are known as routine risk
minimisation measures.
The Summary of Product Characteristics and the Package leaflet for Moxifloxacin Orion can be found in
the national authority’s web page.
This medicine has no additional risk minimisation measures.
VI.2.6 Planned post authorisation development plan
Not applicable.
VI.2.7 Summary of changes to the Risk Management Plan over time
Major changes to the Risk Management Plan over time
Version
Date
Safety Concerns
Comment
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