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VI.2
Elements for a Public Summary
VI.2.1
Overview of disease epidemiology
Schizophrenia is a serious brain illness. It affects around 0.3–0.7% of people at some point in their life.
People with schizophrenia may e.g. hear voices or see things that other people don’t hear or see.
Anyone can develop schizophrenia. It affects men and women equally in all ethnic groups. Teens can
also develop schizophrenia. In rare cases, children have the illness too.
Several factors may contribute to schizophrenia, including:
•
Genes, because the illness runs in families
•
The environment, such as viruses and nutrition problems before birth
•
Different brain structure and brain chemistry.
Bipolar disorder is a serious brain illness. It is also called manic-depressive illness. It affects
approximately 1% of general population. People with bipolar disorder go through unusual mood
changes. Sometimes they feel very happy and “up”, and are much more active than usual. This is
called mania. Sometimes people with bipolar disorder feel very sad and “down”, and are much less
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active. This is called depression. Anyone can develop bipolar disorder. It often starts in a person’s late
teen or early adult years. But children and adults can have bipolar disorder too. The illness usually
lasts a lifetime.
Several factors may contribute to bipolar disorder, including:
•
Genes, because the illness runs in families
•
Abnormal brain structure and brain function.
VI.2.2
Summary of treatment benefits
Quetiapine belongs to a group of medicines called antipsychotics. Quetiapine can be used to treat
several illnesses, such as:
•
Schizophrenia: where you may hear or feel things that are not there, believe things that are
not true or feel unusually suspicious, anxious, confused, guilty, tense or depressed.
•
Mania: where you may feel very excited, elated, agitated, enthusiastic or hyperactive or have
poor judgment including being aggressive or disruptive.
•
Bipolar depression and major depressive episodes in major depressive disorder: where you
may feel sad all the time or you may find that you feel depressed, feel guilty, lack energy, lose your
appetite or can’t sleep.
When quetiapine is being taken to treat major depressive episodes in major depressive disorder, it will
be taken in addition to another drug being used to treat this illness.
The safety and efficacy of quetiapine in above mentioned illnesses has been demonstrated in several
trials.
VI.2.3 Unknowns relating to treatment benefits
There are limited or no data to support the use of this product in patients with decreased kidney or
liver function, in pregnant or breast feeding women, in patients on medicines for their heart or in
epileptic patients on medicines with the substance valproic acid. As studies have mainly been
performed in Caucasians, it is currently unclear whether or not effects may be different in other racial
or ethnic patients. There are also no data currently available on long term use of prolonged release
quetiapine tablets.
VI.2.4
Summary of safety concerns
Important identified risks
Risk
What is known
Preventability
Abnormal muscle movements
In placebo controlled clinical
If these symptoms get serious,
(Extrapyramidal symptoms)
trials quetiapine was associated
doctor should be contacted since
with an increased incidence of
dosage adjustment may be
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Risk
What is known
Preventability
abnormal muscle movements
necessary.
compared to placebo. Abnormal
muscle movements may include
difficulty starting muscle
movements, shaking, feeling
restless or muscle stiffness
without pain. This is most likely
to occur within the first few
weeks of treatment.
Uncontrollable movements,
Uncontrollable movements,
If these symptoms appear after
mainly of face or tongue
mainly of face or tongue may
taking quetiapine, doctor should
(Tardive dyskinesia)
appear when taking quetiapine.
be contacted immediately since
dose reduction or
discontinuation of quetiapine
may be necessary.
Low blood pressure when
Patients taking quetiapine may
Patients should inform their
standing up which may lead to
experience low blood pressure
doctor if they are taking
fainting (Syncope and
when standing up. This may
medicines for high blood
orthostatic hypotension)
make patient feel dizzy or faint
pressure. If symptoms of too
(may lead to falls). Patients
low blood pressure are severe,
taking medicines for high blood
doctor should be contacted.
pressure are at higher risk.
Fits (Seizure)
In controlled clinical trials there
Patients should inform their
was no difference in the
doctor if they have history of
incidence of fits in patients
seizure disorder or have
treated with quetiapine or
conditions associated with
placebo. No data is available
seizures. As with other
about the incidence of seizures
antipsychotics, caution is
in patients with a history of
recommended when treating
seizure disorder.
patients with a history of
seizures.
Disturbance in speech and
Patients taking quetiapine may
If disturbance in speech and
language (Dysarthria)
experience disturbance in
language is severe, doctor
speech and language.
should be contacted.
Very low levels of white blood
Quetiapine should be used with
Low levels of certain type of
white blood cells (Neutropenia)
cells called neutrophils has been
caution in patients who have
uncommonly reported in
had low levels of white blood
quetiapine clinical trials. Most
cells in the past (which may or
cases of severe neutropenia
may not have been caused by
have occurred within a couple of
other medicines). Doctor may
months of starting therapy with
order blood tests to monitor
quetiapine.
white blood cell levels.
Lack of certain type of white
Lack of white blood cells has
Quetiapine should be used with
blood cells (Agranulocytosis)
been rarely reported in
caution in patients who have
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Risk
What is known
Preventability
quetiapine clinical trials.
had low levels of white blood
cells in the past (which may or
may not have been caused by
other medicines). Doctor may
order blood tests to monitor
white blood cell levels.
Weight gain
Weight gain has been seen in
Weight gain should be
patients taking quetiapine.
monitored. Doctor should be
contacted if patient notices
weight gain.
Changes in the amount of
Changes in the amount of
Doctor may order blood tests to
certain fats in the blood (Lipid
certain fats in the blood
monitor changes in the amount
changes /increased cholesterol,
(increases in triglycerides, LDL
of fats in the blood.
increased triglycerides or
and total cholesterol, and
decreased HDLs)
decreases in HDL) have been
observed in clinical trials with
quetiapine.
Increased levels of sugar in the
High blood sugar, in some cases
Doctor should be informed
blood and diabetes
extreme and associated with
before taking quetiapine if
(Hyperglycemia and diabetes
ketones in the blood and urine
patient has experienced high
mellitus)
or coma or death, has been
blood sugar (characterised by
reported in patients treated with
symptoms such as excessive
atypical antipsychotic agents,
thirst, passing of large amounts
including quetiapine. Risk
of urine, increase in appetite,
factors that may predispose
and feeling weak) or has family
patients to severe complications
history of diabetes. Patients
include obesity and family
treated with any antipsychotic
history of diabetes.
agents, including quetiapine,
should be observed for signs
and symptoms of high blood
sugar and patients with diabetes
or with risk factors for diabetes
should be monitored regularly
for worsening of glucose control.
Metabolic risk factors, metabolic
Given the observed changes in
Patients should be monitored for
syndrome
body weight, blood sugar and
worsening of their metabolic risk
blood fats seen in clinical
profile (changes in body weight,
studies, patients (including
blood sugar and blood fats).
those with normal values before
quetiapine treatment) may
experience worsening of their
metabolic risk profile.
Decreases in the amount of
Quetiapine treatment has been
Doctor may order blood tests to
thyroid hormones in the blood
associated with dose-related
monitor thyroid hormone levels
(Hypothyroidism)
decreases in thyroid hormone
if considered necessary.
levels.
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Risk
What is known
Preventability
Increases in the amount of the
Quetiapine may cause increases
Doctor may order blood tests to
hormone prolactin in the blood
in the amount of the hormone
monitor prolactin levels if
(Hyperprolactinemia)
prolactin in the blood. This could
patient experiences such
in rare cases lead to the
symptoms.
following:
- Men and women to have
swelling of breasts and
unexpectedly produce breast
milk.
- Women to have no monthly
period or irregular periods.
Severe allergic reaction which
As with other medicinal
Ketipinor must not be taken if
may cause difficulty in breathing
products, hypersensitivity
patient is allergic to quetiapine
or shock (Anaphylactic reaction)
reactions, characterised by
or any of the other ingredients
allergic symptoms, may occur
of this medicinal product. If
with quetiapine.
patient experiences allergic
symptoms with difficulty in
breathing, medical advice must
be sought immediately.
Yellowing of the skin and eyes,
Yellowing of the skin and eyes,
Before taking quetiapine, doctor
inflammation of the liver and
inflammation of the liver and
should be informed if patient
increased liver enzymes
increased liver enzymes have
has problems with liver. If
(Jaundice, hepatitis, increased
been reported during treatment
patient experiences yellowing of
transaminases and gamma GT
with quetiapine.
the skin and eyes, doctor should
be contacted.
levels)
Severe skin and mucous
Stevens-Johnson syndrome is a
Stevens-Johnson syndrome
membranes disorder (Stevens
rare, serious disorder in which
presents a medical emergency
Johnson Syndrome)
skin and mucous membranes
that usually requires
react severely to a medication or
hospitalization.
infection. Very rare cases of
Steven-johnson syndrome have
been associated with quetiapine.
A combination of fever, severe
A combination of fever, severe
In such cases treatment with
muscle stiffness, sweating or a
muscle stiffness, sweating or a
quetipaine should be stopped
lowered level of consciousness
lowered level of consciousness
and doctor should be contacted
(Neuroleptic malignant
has been associated with
since immediate medical
syndrome)
antipsychotic treatment,
treatment may be needed.
including quetiapine.
Discontinuation (Withdrawal)
Discontinuation symptoms
Gradual withdrawal of
symptoms
(symptoms which occur when
quetiapine over a period of at
patient abruptly stops taking
least 1 to 2 weeks is advisable.
quetiapine) include not being
able to sleep (insomnia), feeling
sick (nausea), headache,
diarrhoea, being sick (vomiting),
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Risk
What is known
Preventability
dizziness, and irritability.
Difficulty swallowing
Difficulty swallowing has been
Quetiapine should be used
(Dysphagia)
reported with quetiapine.
cautiously in patients at risk for
accidental inhalation of food
with risk of pneumonia
(aspiration pneumonia).
Inflammation of the pancreas
Inflammation of the pancreas
Quetiapine should be used with
(Pancreatitis)
has been reported quetiapine.
caution in patients with previous
Many patients had factors which
history of drug induced
are known to be associated with
pancreatitis or other factors
pancreatitis such as increased
known to be associated with
triglycerides, gallstones, and
pancreatitis.
alcohol consumption.
Inappropriate secretion of a
Quetiapine treatment has been
Doctor may order blood tests to
hormone that controls urine
associated with inappropriate
monitor the amount of sodium in
volume and decrease in the
secretion of a hormone that
the blood if considered
amount of sodium in the blood
controls urine volume and
necessary.
(Syndrome of inappropriate
decrease in the amount of
antidiuretic hormone (SIADH)
sodium in the blood.
and hyponatremia)
Blood clots in the veins, which
Cases of venous
Patient should inform doctor if
may travel through blood
thromboembolism have been
patient or someone else in
vessels (Venous
reported with antipsychotic
patient’s family has a history of
thromboembolism)
drugs. This means that there is
blood clots.
a risk for formation of blood
If patient notices any of these
clots in the veins especially in
symptoms, medical advice
the legs (symptoms include
should be sought immediately.
swelling, pain and redness in the
leg), which may travel through
blood vessels to the lungs
causing chest pain and difficulty
in breathing.
Specific change in electrical
QT prolongation has been
Before taking quetiapine,
activity of the heart seen on
reported with quetiapine at the
patients should inform doctor if
ECG (Prolonged QT)
regular doses and in overdose.
they, or someone in their family,
has or has had any heart
problems such as a very fast
heart beat or prolonged QT on
an ECG (heart tracing), or if
patient uses medicines that
have an impact on the way
heart beats, for example,
medicines that can cause an
imbalance in electrolytes (low
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Risk
What is known
Preventability
levels of potassium or
magnesium) such as diuretics
(water pills) or certain
antibiotics (medicines to treat
infections).
In the children and adolescents
Increases in blood pressure
Blood pressure should be
population only: increased blood
have been reported in children
monitored in the children and
pressure
and adolescents in clinical trials.
adolescents taking quetiapine.
Important potential risks
What is known (Including reason why it is considered a
Risk
potential risk)
Certain heart rhythm disorder
The class of medicines to which quetiapine belongs can cause heart
(Torsades de Pointes)
rhythm problems, which can be serious and in severe cases may be
fatal.
Use in elderly patients
As with other antipsychotics, quetiapine should be used with
caution in the elderly, especially during the initial dosing period
since elderly patients may be more susceptible to adverse drug
reactions.
Increased mortality in elderly
Increased risk of stroke, or in some cases the risk of death, in
patients with dementia
elderly people with dementia (loss of brain function) have been
noted in clinical trials with the class of medicines to which
quetiapine belongs.
Conditions that develop as a
Increased risk of stroke, or in some cases the risk of death, in
result of problems with the blood
elderly people with dementia (loss of brain function) have been
vessels inside the brain in
noted in clinical trials with the class of medicines to which
elderly patients (Cerebrovascular
quetiapine belongs. Similar increase of risk in other patient groups
adverse effects in elderly
have not been excluded.
patients)
Conditions that develop as a
Increased risk of stroke, or in some cases the risk of death, in
result of problems with the blood
elderly people with dementia (loss of brain function) have been
vessels inside the brain in the
noted in clinical trials with the class of medicines to which
non-elderly (Cerebrovascular
quetiapine belongs. Similar increase of risk in other patient groups
adverse effects in the non-
have not been excluded.
elderly)
Condition caused by excessive
Cases of serotonin syndrome have been reported. Serotonin
serotonergic activity in the
syndrome is potentially life-threatening condition requiring medical
nervous system (Serotonin
treatment.
syndrome)
Sudden death
Cases of sudden unexplained death have been reported with the
class of medicines to which quetiapine belongs.
Inflammation of the heart
Cases of myocarditis have been reported with the class of
muscle (Myocarditis)
medicines to which quetiapine belongs. Myocarditis is potentially
life-threatening condition requiring medical treatment.
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What is known (Including reason why it is considered a
Risk
potential risk)
Heart disease characterized by
Quetiapine should be used with caution in patients with known
reduced blood supply to the
heart disease since quetiapine has effects on blood pressure.
heart (Ischemic heart disease)
Clouding of the lens inside the
Cases of cataract have been reported with the class of medicines to
eye which leads to a decrease in
which quetiapine belongs.
vision (Cataract)
Aggression/agitation
Cases of aggression/agitation have been reported with the class of
medicines to which quetiapine belongs.
Potential for off-label use (use
Such as other medicinal products, quetiapine has potential for off-
for an unapproved indication or
label use and misdosing if product information regarding indications
in an unapproved age group)
and posology are not followed.
and misdosing
Use in patients with hepatic
If patient suffers from hepatic impairment, the amount of
impairment
quetiapine in blood may be increased. Therefore it might be needed
to lower the dose of quetiapine.
Treatment emergent mania in
Cases of treatment emergent mania in bipolar disorder have been
bipolar disorder
reported with quetiapine.
Abuse and misuse
Such as other medicinal products affecting central nervous sytem,
quetiapine has potential for abuse and misuse if product
information regarding indications and posology are not followed.
Suicide
Depressed patients may sometimes have thoughts of harming or
killing yourself. These may be increased when first starting
treatment, since these medicines all take time to work, usually
about two weeks but sometimes longer.
Fall (Accidental injury)
Quetiapine treatment has been associated with low blood pressure
when standing up which may lead to fainting. This could increase
the occurrence of accidental injury (fall), especially in the elderly
patients.
Accidental inhalation of food with
Quetiapine should be used cautiously in patients at risk for
risk of pneumonia (Aspiration
accidental inhalation of food with risk of pneumonia (aspiration
pneumonia)
pneumonia) since quetiapine may cause difficulty in swallowing.
Missing information
Risk
What is known
Use in patients with renal
According to current knowledge, dosage adjustment is not
impairment
necessary in patients with renal impairment.
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Use in pregnant and lactating
The safety and efficacy of quetiapine during human pregnancy and
women
breastfeeding have not yet been established. Patient should not
take quetiapine during pregnancy unless this has been discussed
with your doctor. Quetiapine should not be taken if patient is
breast-feeding.
Use in patients of different or
There might be a need for dosage adjustment in in patients of
certain ethnic or racial origin
different or certain ethnic or racial origin due to different drug
metabolism.
Use in patients on concomitant
Formal interaction studies with commonly used cardiovascular
cardiovascular medications
medicinal products have not been performed.
Use in patients on concomitant
According to case reports there might be potential for an
valproic acid
interaction between quetiapine and valproic acid.
Long-term exposure
Long-term efficacy and safety in patients with major depressive
disorder has not been evaluated as add-on therapy, however longterm efficacy and safety has been evaluated in adult patients as
monotherapy.
Use in patients with hepatic
If patient suffers from hepatic impairment, the amount of
impairment
quetiapine in blood may be increased. Therefore it might be needed
to lower the dose of quetiapine.
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 Ketipinor
can be found in the national authority’s web page.
This medicine has also special conditions and restrictions for its safe and effective use (additional risk
minimisation measures).
These additional risk minimisation measures are for the following risks:
Weight gain
Risk minimisation measure(s)
Objective and rationale
Healthcare professionals (HCPs) to understand the risk of weight gain and the procedures related to
the appropriate management of this risks to minimize its occurrence and its severity.
Main additional risk minimisation measure
HCP educational materials to be provided to prescribers.
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Changes in the amount of certain fats in the blood (Lipid changes /increased cholesterol)
Risk minimisation measure(s)
Objective and rationale
Healthcare professionals (HCPs) to understand the risk of lipid changes /increased cholesterol and the
procedures related to the appropriate management of this risks to minimize its occurrence and its
severity.
Main additional risk minimisation measure
HCP educational materials to be provided to prescribers.
Increased levels of sugar in the blood and diabetes (Hyperglycemia and diabetes mellitus)
Risk minimisation measure(s)
Objective and rationale
Healthcare professionals (HCPs) to understand the risk of hyperglycemia and diabetes mellitus and the
procedures related to the appropriate management of this risks to minimize its occurrence and its
severity.
Main additional risk minimisation measure
HCP educational materials to be provided to prescribers.
Metabolic risk factors, metabolic syndrome
Risk minimisation measure(s)
Objective and rationale
Healthcare professionals (HCPs) to understand the risk of metabolic risk factors/metabolic syndrome
and the procedures related to the appropriate management of this risks to minimize its occurrence and
its severity.
Main additional risk minimisation measure
HCP educational materials to be provided to prescribers.
VI.2.6 Planned post authorisation development plan (if applicable)
Not applicable.
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