Download VI.2 Elements for a Public summary VI.2.1 Overview of disease

VI.2 Elements for a Public summary
VI.2.1
Overview of disease epidemiology
Infections like endocarditis, infections of the bones (osteomyelitis), pneumonia, soft tissue
infections are often difficult to treat. The epidemiology of infectious disease varies according to
the organism but in general occur in vulnerable groups, particularly the elderly and those with
impaired resistance to infection. All age groups may be affected. Vancomycin is used
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particularly in infections which are resistant to the use of other antibiotics and these are
commonly found in hospital patients.
VI.2.2
Summary of treatment benefits
Vancomycin effectively treats a variety of bacterial infections which cannot be treated effectively
by more commonly used drugs. It is especially useful for very ill and vulnerable patients who
need intensive treatment and so is most frequently used in intensive care units. This includes
patients with severe infections of the blood stream and patients with severe infections following
operation. The effectiveness varies from patient to patient and the treatment dose has to be
carefully adjusted with the help of experts in the treatment of the disease.
VI.2.3
Unknowns relating to treatment benefits
There are no significant unknowns as vancomycin is a drug which has been used for many years
so that its role in treatment is well-defined.
VI.2.4
Summary of safety concerns
The safety concerns of vancomycin have been well documented based on many years clinical use.
There are no outstanding concerns or new signals that relate to this generic product. Known
serious possible hazards (identified risks) according to the SmPC of the Brand Leader are detailed
in the table below along with the appropriate risk-minimisation measures in the Section
“Summary of risk minimisation measures by safety concern”.
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Important identified risks
RISKS
WHAT IS KNOWN
PREVENTABILITY
Hypersensitivity to vancomycin.
This is a very infrequent problem. Patients with
frequent allergies are more at risk and should mention
this to the healthcare professional.
Concomitant administration of vancomycin and
anaesthetic agents has been associated with marked red
flushing of the skin in children.
Reports have shown that this occurs more frequently
when the young patient is given an anaesthetic agent.
Toxicity at injection sites.
Vancomycin when not being administered correctly can
cause pain at the injection site and sometimes the
surrounding tissues may die.
Avoiding the product when allergies to
vancomycin or other substances in the tablet are
known will avoid the problem in most cases.
Concomitant administration of vancomycin and an
anaesthetic agent should be avoided whenever
possible.
Infusion-related reactions may be minimised by
giving vancomycin slowly (over 60 minutes)
before the anaesthetic is given.
The problem may be avoided by infusing slowly
(for more than 60 minutes). Your doctor should
consult the information leaflet to ensure its correct
administration.
Difficulty in controlling the
dose as small changes may lead
to toxic effects or to a lack of
effectiveness (this is called “a
narrow therapeutic index”).
Small increases of vancomycin dose may result in it a
toxic effect, especially when your kidney is not
functioning optimally. On the other hand modest dose
reductions may lead to the blood levels being too low
for the drug to be effective in fighting the infection.
This is especially evident in very old or very young
patients.
The natural decrement of kidney function with
increasing age may lead to elevated amount of
vancomycin retained in the bloodstream.
There are marked differences in dose requirements for
This problem can be avoided by measuring the
levels of vancomycin in the blood by experts as
necessary. which should be closely monitored and
the doses adjusted.
Adjustment of the dosage and ensure blood
concentrations are carefully monitored.
Vancomycin should always be administered to
neonates and infants by experts according to
established dosing regimes. Monitoring blood
levels of vancomycin allows your doctor to
establish correct serum levels to effectively treat
the infection while avoiding too high a dose.
RISKS
Development of red neck
syndrome (Red Man
Syndrome).
Toxicity to the gastrointestinal
tract, causing inflammation of
the colon (colitis).
WHAT IS KNOWN
PREVENTABILITY
vancomycin the first months and years of life. In
premature neonates and young infants, it may be
appropriate to confirm the desired amount of
vancomycin remaining in the blood. The time taken for
the amount of vancomycin to be halved (known as the
half-life) ranges from approximately 2 to 10 hours
depending on age. There is an approximately two fold
difference in their half-lives, between patients aged 3
months to 4 years old compared to those older than 4
years which can lead to a huge difference in the dosing
strategies of vancomycin.
This is a combination of flushing and/or a red rash that
affects the face, neck, and upper torso. Less frequently,
low blood pressure and swelling of the tissues especially
around the mouth and throat may also occur. It usually
appears within 4–10 minutes after the commencement
or soon after the completion of an injection directly into
your bloodstream (an infusion).
In very rare cases, you may suffer from a serious bowel
condition. This may occur when vancomycin kills the
usual bacteria in your bowel leading to an overgrowth
of harmful bacteria. These bacteria are toxic to the
bowel wall and may lead to abdominal pain and bloody
diarrhoea. This condition ( which is called antibioticassociated colitis or pseudomembranous colitis) may
vary from mild effects with minimal diarrhoea to
dramatic diarrhoea with bleeding which can be lifethreatening. Less than 1 out of 10,000 patients treated
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Your doctor will administer vancomycin in a dilute
solution slowly, over at least 60 minutes
(maximum rate of 10 mg/minute for doses
>500 mg). This is due to the high incidence of pain
and thrombophlebitis and to avoid an infusion
reaction known as the red man syndrome or red
neck syndrome. Symptoms may be treated or
prevented with antihistamines, including
diphenhydramine, and are less likely to occur with
slow infusion.
It is important that your doctor considers the
diagnosis of antibiotic-associated colitis or
pseudomembranous colitis in patients who
suffer from diarrhoea during or subsequent to
the administration of vancomycin. Discontinuation
of therapy with vancomycin and early start of a
specific treatment should be considered. Medicinal
products that inhibit gut motility (peristalsis)
should not be given.
RISKS
WHAT IS KNOWN
PREVENTABILITY
with vancomycin may develop this more serious form.
Use in pregnancy and lactation. There is not sufficient safety experience available
regarding the use of vancomycin during human
pregnancy to ensure its safety during pregnancy.
Studies in animals do not suggest any ill effects on the
development of the embryo, foetus or gestation period.
However Vancomycin penetrates the placenta and a
potential risk of embryonal and neonatal toxicity cannot
be excluded.
Vancoymcin is excreted in human milk
Toxicity to the kidney especially The body excretes vancomycin through the kidneys and
in patients with reduced kidney if these are not working properly vancomycin levels in
function (renal insufficiency) or the body increase. In the first 24 hours, about 75% of
those receiving other drugs
an administered dose of vancomycin is excreted in urine
which may be toxic to the
by the kidney. Thus if the kidneys are not working
kidneys.
adequately the vancomycin may accumulate in the
blood. This accumulation of vancomycin in the blood
stream leads to an increased risk of toxicity to the
kidney.
If you receive medicines that can cause damage to your
kidneys, vancomycin can make these problems worse
Toxicity to the ears (ototoxicity)
especially in patients who
already have some hearing loss,
or those receiving other drugs
which may be toxic to the ears.
Vancomycin is known to be a drug that can affect
hearing. It is not clear what the exact risk of this is but
reports of cases in which patient’s hearing is affected
are rare. In patients whose kidneys are not functioning
normally and in patients taking other drugs known to
affect hearing (especially antibiotic drugs known as
aminoglycosides) the risk of hearing damage is higher.
If you receive medicines that can cause damage to your
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The problems associated with the use of
vancomycin in pregnancy or breastfeeding can be
avoided only by ensuring that the drug is not given
during pregnancy. It should be only given if
absolutely necessary, and only after careful
discussion with between the patient and the expert
prescriber, with consideration of all the potential
risks. Vancomycin should only be considered only
if other antibiotics have failed.
If you have kidney disease it is important to inform
your doctor before being treated with vancomycin.
This will allow the dose you take to be carefully
adjusted or complete avoidance. Careful
monitoring can prevent the occurrence of serious
problems.
Your doctor will know which medicines may cause
kidney problems and should avoid prescribing
these with vancomycin. If the combination is
unavoidable careful monitoring of vancomycin
levels is recommended, along with kidney function
tests to detect any potential issues.
Vancomycin is best avoided in individuals at
increased risk of hearing damage such as those
with existing hearing loss, those with poorly
functioning kidneys and those taking other drugs
(such as aminoglycoside antibiotics) which may
damage hearing. When it is essential to give the
drug it should be given cautiously and blood levels
should be monitored carefully. These precautions
RISKS
WHAT IS KNOWN
PREVENTABILITY
hearing, vancomycin can make these problems worse.
Severe skin reactions
Very rarely (1<10,000) vancomycin can cause fluidfilled blisters. Blistering may be localised and mild, or
widespread and severe, even life-threatening.
When vancomycin is uses in
patients receiving drugs given
to relax the muscles (called
neuromuscular blocking agents
and often given during surgical
operations) , there may be an
increase in the relaxation of the
muscles and paralysis may
occur
Giving vancomycin and a neuromuscular blocking agent
at the same time has been shown to increase the effects
on muscles leading to too much muscle relaxation. This
can cause breathing to be affected for a longer period
than required for the operation so making recovery after
the operation difficult.
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will minimise the occurrence and limit the extent of
any hearing loss.
Your doctor will know which medicines may cause
hearing problems and avoid prescribing these with
vancomycin. If the combination is unavoidable,
careful monitoring of vancomycin levels is
recommended, along with hearing tests to detect
any potential issues.
IF you experience any skin problems whilst on
vancomycin, inform your doctor at once. Your
doctor may decide to discontinue vancomycin or
offer treatment to help improving the skin
problems.
Neuromuscular blocking agents are often only used
in surgical procedures or in a hospital. Patients
receiving vancomycin are also treated in hospital .
It can be necessary to administer these drugs at the
same time. This situation can be managed by your
doctors who need to use considerable caution
requiring dosage and need to monitor the response
of the muscles carefully.
Important potential risks
None
Missing information
None
VI.2.5
Summary of risk minimisation measures by safety concern
Safety concern
Proposed pharmacovigilance
activities (routine and
additional)
Proposed risk
minimisation
activities (routine
and additional)
Routine
pharmacovigilance
activities
are
considered
sufficient and no further
actions are required.
Important identified
risks are adequately
described in the
product information.
No further risk
management
activities are
necessary.
Important identified risks










Hypersensitivity reactions.
Toxicity at injection sites.
Narrow therapeutic index
(resulting in possible
underdosing or overdosing)
Developing Red Man syndrome.
Toxicity to the gastrointestinal
tract, causing colitis.
Use in pregnancy and lactation.
Nephrotoxicity especially in
patients with renal
insufficiency.
Ototoxicity especially in
patients with previous hearing
loss.
Severe bullous skin reactions
Increase in neuromuscular
blockage when used
concomitantly with
neuromuscular blocking agents.
These additional risk minimisation measures are for the following risks:
VI.2.6
Planned post authorisation development plan
At present, there is no plan to clinical develop vancomycin further than up to the status within the
current marketing authorisation procedure.
VI.2.7
Summary of changes to the Risk Management Plan over time
This is the first risk management plan for vancomycin therefore no changes to the previous
version can be addressed.
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