VI.2. Elements for a Public Summary RISPERDAL belongs to a ... · RISPERDAL improved the symptoms of dementia compared with placebo in 3 short-term trials in 1,150 elderly adults

RISPERDAL (oral risperidone) and RISPERDAL CONSTA (risperidone long-acting injection)Risk Management Plan Version 2.0

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Safety Concern

Risk Minimisation Measures

Routine Additional

Missing Information:

Use in patients with renal impairment, including those requiring haemodialysis

The safety of RISPERDAL has not been systematically studied in patients with renal impairment, including those who require haemodialysis.

The SmPC provides special RISPERDAL dosing instructions in Section 4.2 for patients with renal impairment, warns in Section 4.4 that RISPERDAL should be used with caution in renally impaired patients, and describes the results of a relevant pharmacokinetics study in Section 5.2.

None proposed

Use in hepatic impairment

Safety of RISPERDAL has not been systematically studied in patients with hepatic impairment.

The SmPC provides special RISPERDAL dosing instructions in Section 4.2 for patients with hepatic impairment, warns in Section 4.4 that RISPERDAL should be used with caution in hepatically impaired patients, and describes the results of a relevant pharmacokinetics study in Section 5.2.

None proposed

Use during pregnancy

Safety of RISPERDAL has not been established in pregnancy, as indicated in SmPC Section 4.6. As stated Section 5.3, the potential risks for humans based on preclinical safety data are unknown.

Newborns should be monitored carefully if risperidone is taken during pregnancy.

RISPERDAL should not be used during pregnancy unless clearly necessary. If discontinuation of RISPERDAL during pregnancy is necessary, it should not be done abruptly.

None proposed

Use in nursing mothers

Safety of RISPERDAL has not been established in nursing mothers, as indicated in Section 4.6 in the SmPC. Section 4.6 states that in animal studies, risperidone and 9-hydroxy-risperidone are excreted in the milk. It has been demonstrated that risperidone and 9-hydroxy-risperidone are also excreted in human breast milk in small quantities. No data are available on adverse reactions in breast-feeding infants. Therefore, the advantage of breast-feeding should be weighed against the potential risks for the child.

None proposed

Key: SmPC=Summary of Product Characteristics

VI.2. Elements for a Public Summary

RISPERDAL belongs to a group of medicines called atypical antipsychotics.

RISPERDAL is used to treat the following:


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Schizophrenia (in adults), where you may see, hear, or feel things that are not there;

believe things that are not true; or feel unusually suspicious or confused.

Mania (in adults), where you may feel very excited, elated, agitated, enthusiastic, or

hyperactive. Mania occurs in an illness called bipolar disorder.

Short-term treatment (up to 6 weeks) of long-term aggression in people with Alzheimer’s

dementia, who are at risk of harming themselves or others. Alternative (non-drug)

treatments should have been tried before starting patients on RISPERDAL.

Short-term treatment (up to 6 weeks) of long-term aggression in intellectually disabled

children (at least 5 years of age) and adolescents with conduct disorder.

RISPERDAL is available as a tablet to be swallowed, a tablet that dissolves in the mouth, and as

a liquid.

VI.2.1. Overview of Disease Epidemiology

Schizophrenia is a disorder with symptoms such as hearing voices, seeing or sensing things that

are not there, mistaken beliefs, unusual suspiciousness, becoming withdrawn, incoherent speech,

and behaviour and emotional flatness. People with this disorder often may also feel depressed,

anxious, guilty, or tense. The World Health Organisation estimates that there are 24 million

people with schizophrenia worldwide or approximately 1% of the general population.

Schizophrenia usually appears in men between 20 and 24 years of age and appears in women

between 29 and 32 years of age. Schizophrenia is more common in men than in women.

Schizophrenia is a chronic disease and is one of the leading causes of disability worldwide.

People with schizophrenia are at increased risk of having other health problems, including

substance abuse, alcohol abuse and smoking.

Mania affects 0.4% to 1.6% of the general population worldwide. Bipolar disorder affects 5% to

7% of the population. Bipolar I disorder affects men and women equally while bipolar II disorder

is more common in women than in men.

Aggression occurs in about 20% of people with Alzheimer’s disease who are not in care facilities

and in about 40% to 60% of people in care facilities. Of patients with Alzheimer’s disease, 44%

are 75 to 84 years of age and 46% are older than 85 years of age. Dementia affects men and

women equally.

Studies have found that the rate of conduct disorder can range from less than 1% to more than

10% of the general population of children and adolescents. While conduct disorder is uncommon

in childhood, the rate of diagnosis increases steeply from late childhood to the early teens.

VI.2.2. Summary of Treatment Benefits

The main treatment for schizophrenia is the use of antipsychotic medicines. Newer, atypical

antipsychotics are usually preferred over older, typical antipsychotics because they have fewer

side effects on the nervous system. In addition to the use of medicine, psychosocial treatments


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such as therapy, work training, and life skills training are also important in the long-term

management of schizophrenia.

Medications for bipolar disorder include lithium (standard treatment), mood stabilisers,

antipsychotics, antidepressants, and antianxiety medications.

RISPERDAL improved the symptoms of schizophrenia compared with placebo (a dummy treatment) in 3 short-term (4 to 8 weeks of treatment) trials in adults with schizophrenia. After 8 weeks of treatment, higher doses of RISPERDAL showed more benefit than a lowdose in 1 trial of adults with schizophrenia.

RISPERDAL was more effective than haloperidol in preventing the return of symptoms of schizophrenia in 1 long-term (1 to 2 years of treatment) trial in adults with schizophrenia who had been stabilised on an antipsychotic medicine for at least 4 weeks.

RISPERDAL improved the symptoms of mania compared with placebo in 3 short-term (3 weeks of treatment) trials in approximately 820 adults with bipolar I disorder. In 1 trial continued through 12 weeks, symptom improvement was maintained

In 2 short-term trials, either RISPERDAL or placebo were used with mood stabilisers in approximately 300 adults with bipolar I disorder. After 3 weeks of treatment, RISPERDAL was more effective in improving the symptoms of mania than placebo in one trial but not in the other.

RISPERDAL improved the symptoms of dementia compared with placebo in 3 short-term trials in 1,150 elderly adults with dementia.

RISPERDAL improved the symptoms of conduct disorder in 2 short-term (6 weeks of treatment) trials in approximately 240 children (5 to 12 years old) with a conduct disorder.

VI.2.3. Unknowns Relating to Treatment Benefits

There is either no or only limited information about the use of RISPERDAL in patients with

kidney problems (including those who need dialysis [a treatment for people whose kidneys no

longer work]), patients with liver problems, pregnant women, and breastfeeding women.


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VI.2.4. Summary of Safety Concerns

Important Identified Risks

Risk What is known Preventability

High levels of a hormone called “prolactin” found on a blood test (Hyperprolactinaemia and potentially prolactin-related events)

RISPERDAL, as with other antipsychotic medicines that affect dopamine levels in the brain, can raise levels of a hormone called prolactin found on a blood test.

A high level of prolactin in the blood may or may not cause symptoms. When symptoms of high prolactin occur in men, they may include breast swelling, difficulty in getting or maintaining erections, other problems with sexual performance, or changes in the ability to produce children. In women, symptoms may include breast discomfort, leakage of milk from the breasts, missed menstrual periods, other problems with the menstrualcycle, or changes in the ability to produce children.

Special care with RISPERDAL is needed in patients who already have an abnormally high level of the hormone prolactin in the blood before treatment or if they have a possible prolactin-dependent tumour (for example, a tumour in the pituitary gland in the brain). A doctor may order a blood test of prolactin for a patient who is experiencing symptoms that might be related to high levels of prolactin. As with all medications, a patient’s doctor may decide to stop treatment with RISPERDAL if the risks are considered to outweigh the benefits in an individual patient. Apatient should not stop taking RISPERDAL without discussing this with the doctor who prescribed it.

An increase in time of contraction and relaxation of the heart ventricles found on an electrical tracing of heart activity

(QT prolongation)

QT prolongation was reported uncommonly, in 0.1% to 1% of patients taking RISPERDAL.

There is a very small chance that this may lead to more serious heart problems, such as abnormal heart rhythms (‘arrhythmias’), particularly in patients with underlying heart problems that could increase their risk of death from such conditions.

Special care with RISPERDAL is needed in patients with certain heart problems or other conditions that may increase the risk for QT prolongation such as a family history of QT prolongation.Special care is needed when using RISPERDAL along with medicines that:

may change the electrical activity of the heart, such as medicines for malaria, heart rhythm problems, allergies (antihistamines), some antidepressants or other medicines for mental problems

cause a slow heart beat

cause low blood potassium (such as certain diuretics).


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Low blood pressure upon standing

(Orthostatic hypotension)

Orthostatic hypotension is a side effect of some atypical antipsychotic medicines, including RISPERDAL.

Some people taking RISPERDAL may feel faint, dizzy, or may pass out when they stand up or sit up suddenly.

Elderly patients are at a higher risk for orthostatic hypotension.

Special care with RISPERDAL is needed in patients with certain heart problems. Examples include patients with an irregular heart rhythm, patients prone to low blood pressure, or patients using medicines to treat raised blood pressure. RISPERDAL may cause low blood pressure. The dose may need to be adjusted.

Slow or impaired movement or uncontrollable muscle movements

(Extrapyramidal symptoms/tardive dyskinesia)

Extrapyramidal symptoms/tardive dyskinesia are side effects of atypical antipsychotic medicines, including RISPERDAL.

Extrapyramidal symptoms may include a sensation of stiffness or tightness of the muscles, a slow shuffling walk, a loss of expression on the face, restlessness, abnormal movements of the eyes, mouth, tongue, or jaw, and repetitive, spastic, or writhing movements.

Some extrapyramidal symptoms were reported in 1 to 10% of patients taking RISPERDAL, while other extrapyramidal symptoms were reported in more than 10% of patients taking RISPERDAL.

There is also a small risk (between 0.1% and 1% of patients taking RISPERDAL) of a more serious movement disorder called tardive dyskinesia, which involves uncontrollable twitching or jerking movements in the face, tongue, or other parts of the body.

RISPERDAL should be used carefully in patients who have experienced movement problems in the past, including Parkinson’s disease or dementia with Lewy bodies.Special care with RISPERDAL is needed in patients who have ever experienced involuntary movements of the tongue, mouth, and face.A patient needs to tell his/her doctor immediately if he/she experiences involuntary rhythmic movements of the tongue, mouth, and face. Withdrawal of RISPERDAL may be needed.Children and adolescents treated with RISPERDAL should be checked by their doctor regularly for extrapyramidal symptoms and other movement disorders.In patients who require long-term treatment, the aim is to control symptoms with the smallest dose and the shortest duration of treatment.


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A condition with symptoms that include high temperature, muscle stiffness, sweating, or a lowered level of consciousness

(Neuroleptic malignant syndrome)

Neuroleptic malignant syndrome is a rare but serious side effect that could be fatal and has been reported with RISPERDAL and similar medicines. Neuroleptic malignant syndrome occurs rarely (in 0.01% to 0.1% of patients taking RISPERDAL).

Special care with RISPERDAL is needed in patients who have ever had Neuroleptic malignant syndrome.Patients need to tell their doctor immediately if they experience fever, muscle stiffness, shaking, sweating more than usual, more than usual, increased heart rate or blood pressure, or muscle pain or weakness, confusion, or a lowered level of consciousness. Immediate medical treatment may be needed.All antipsychotics should be discontinued if a patient develops signs or symptoms of Neuroleptic malignant syndrome.

Diabetes or problems due to a high blood sugar level

(Diabetes mellitus and hyperglycaemia-related adverse events)

Diabetes mellitus or worsening of pre-existing diabetes mellitus have been seen with patients taking RISPERDAL.

With RISPERDAL, high blood sugar was observed in 0.1% to 1% of patients and diabetes in 0.1% to 1% of patients. Risk factors for diabetes include being overweight or having a family history of diabetes.

Patients treated with RISPERDAL should be checked by their doctor for signs of high blood sugar. Special care with RISPERDAL is needed in patients with diabetes and blood glucose should be monitored regularly in these patients.In patients at increased risk of cardiovascular disease, blood glucose should be monitored regularly.

An increase in body weight

(Weight gain)

Significant weight gain may adversely affect health.

Patients with schizophrenia may be at higher risk for weight gain due to poor dietary choices and decreased levels of physical activity. Weight gain was reported in 1% to 10% of patients taking RISPERDAL.

Before RISPERDAL treatment is started, body weight should be measured and it should be regularly monitored during treatment.By monitoring body weight, especially in patients at increased risk of cardiovascular disease or diabetes mellitus. Lifestyle measures (such as change in diet and increase in exercise) should be considered early if patients experience significant weight gain.


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Convulsion (fits)

(Seizures)

Convulsions were reported uncommonly, in 0.1% to 1% of patients taking RISPERDAL.

Special care with RISPERDAL is needed in patients with epilepsy, in patients who have ever had seizures, or in patients with an increased risk for seizures.

Feeling sleepy or less alert

(Somnolence)

Feeling sleepy or less alert was reported in more than 10% of patients taking RISPERDAL.

This may affect the ability to drive a car, operate machines, or do other things that require alertness. These problems are more likely to happen if RISPERDAL taken in combination with other medicines (or alcohol) that work in the brain.

Special care is needed when using RISPERDAL along with medicines that work on the brain to help patients calm down such as (benzodiazepines) or some medicines for pain (opiates), medicines for allergy (some antihistamines), as RISPERDAL may increase the sedative effect of all of these.

Special care is needed when using RISPERDAL along with alcohol, as RISPERDAL may increase its sedative effect.

If tiredness occurs during RISPERDAL treatment of children or adolescents, a change in the time of administration might improve attention difficulties.

Since tiredness may occur during treatment with RISPERDAL, patients should not drive or use any tools or machines without talking to their doctor first.

A prolonged or painful erection(Priapism)

Priapism was reported rarely, in 0.01% to 0.1% of patients taking RISPERDAL.

Special care with RISPERDAL is needed in men who have ever had a prolonged or painful erection.

Men treated with RISPERDAL need to tell their doctor immediately if they experience a prolonged or painful erection. Immediate medical treatment may be needed.


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Stroke or “mini” stroke

(Cerebrovascular accident)

It is not known how often strokes occur in patients with schizophrenia who do not receive treatment.

Sudden loss of blood supply to the brain (stroke or "mini" stroke) was reported uncommonly, in 0.1% to 1% of patients taking RISPERDAL.

Blood vessel problems in the brain were reported rarely, in 0.01% to 0.1% of patients taking RISPERDAL.

Special care with RISPERDAL is needed in patients with any factors which would favour having a stroke, such as high blood pressure, cardiovascular disorder, or blood vessel problems in the brain.

Patients with dementia caused by stroke should not take RISPERDAL.

Medical treatment should be sought straight away if a patient or caregiver notices a sudden change in mental state or sudden weakness or numbness of the face, arms or legs, especially on one side, slurred speech, or speech or vision problems, even for a short period of time. These may be signs of a stroke.

Blood clots in the veins, typically in the legs (“DVT”). In some cases (i.e., a venous thromboembolism), these clots may travel to the lungs

(Venous thromboembolism)

With RISPERDAL, blood clots in veins and lungs have been reported rarely, in 0.01% to 0.1% of patients.

Special care with RISPERDAL is needed if a patient or someone else in their family has a history of blood clots.

Patients should seek medical advice immediately if they experience blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness in the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty breathing.

White blood cell count decreased

(Leukopenia)

Low numbers of a certain type of white blood cell needed to protect the body against infection have been reported with RISPERDAL.

Special care with RISPERDAL is needed in patients who have had low levels of white blood cells in the past (which may or may not have been caused by other medicines). White blood counts should be monitored.

A patient’s doctor may decide to stop RISPERDAL treatment if there is a serious decrease in white blood cells without a known cause.


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A dangerously low number of a certain type of white blood cell needed to fight infection

(Agranulocytosis)

With RISPERDAL, agranulocytosis has been reported rarely, in 0.01% to 0.1% of patients.

Special care with RISPERDAL is needed in patients who have had low levels of white blood cells in the past (which may or may not have been caused by other medicines). White blood counts should be monitored.

Patients should be carefully monitored for fever or other symptoms of infection and treated promptly.

For serious cases, a patient’s doctor should stop RISPERDAL treatment and monitor white blood cell counts until the patient recovers.

A decrease in platelets, the type of blood cell that helps stop bleeding

(Thrombocytopenia)

A decrease in platelets was reported in 0.1% to 1% of patients taking RISPERDAL. Often, decreased platelet levels do not cause problems, but can increase the risk of bruising, nosebleeds and/or bleeding gums. Patients with low platelets may also feel more weak and tired than usual.

Platelet counts and symptoms can be monitored during treatment with RISPERDAL.

In most cases when this condition is caused by a medicine, stopping the medicine leads to recovery.

Breakdown of muscle fibres and pain in muscles

(Rhabdomyolysis)

This condition was reported rarely (in 0.01% to 0.1% of patients taking RISPERDAL).

If rhabdomyolysis occurs, a patient’s doctor should stop all antipsychotic medications, including RISPERDAL.

By monitoring for early symptoms. If a patient develops signs or symptoms indicative of Neuroleptic Malignant Syndrome, including rhabdomyolysis,all antipsychotics should be discontinued.


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Increased risk of death in elderly patients with dementia

(Overall increased mortality in elderly patients with dementia)

Increased risk of death in elderly patients with dementia is a safety concern with some atypical antipsychotic medicines, including RISPERDAL.

Special care with RISPERDAL is needed in patients with dementia.

During treatment with RISPERDAL, elderly patients with dementia should frequently see their doctor.

Special care is needed when using RISPERDAL along with water tablets (diuretics, such as furosemide) used for heart problems or swelling of parts of your body due to a build-up of too much fluid. RISPERDAL, taken by itself or with furosemide, may have an increased risk of stroke or death in elderly patients with dementia.

Elderly patients with dementia should avoid becoming dehydrated since this was a factor in the increased risk of death in these patients.

Stroke or “mini” stroke in elderly patients with dementia

(Cerebrovascular adverse events in elderly patients with dementia)

Stroke or “mini” stroke in elderly patients with dementia is a safety concern with some atypical antipsychotic medicines, including RISPERDAL.

In elderly patients with dementia, there is an increased risk of stroke or “mini” stroke with RISPERDAL.

In clinical trials with RISPERDAL in elderly patients with dementia, 1.4% of patients had a “mini” stroke and 1.5% of patients had a stroke.

Special care with RISPERDAL is needed in patients with dementia. RISPERDAL taken by itself or with furosemide, may have an increased risk of stroke or death in elderly patients with dementia.

Patients with dementia caused by stroke should not take RISPERDAL.

During treatment with RISPERDAL, elderly patients with dementia should frequently see their doctor.

Special care with RISPERDAL is needed in patients with any factors which would favour having a stroke, such as high blood pressure, cardiovascular disorder, or blood vessel problems in the brain.

Medical treatment should be sought straight away if a patient or care-giver notice a sudden change in mental state or sudden weakness or numbness of the face, arms or legs, especially on one side, or slurred speech, even for a short period of time. These may be signs of a stroke.


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Important Potential Risks

RiskWhat is known (Including reason why it is considered a potential risk)

Cancer of the pituitary gland, pancreas, or breast

(Carcinogenicity [pituitary adenomas; endocrine pancreas tumours; breast cancer])

Information gathered with RISPERDAL and similar medicines has not shown that people who take them are at any increased risk of developing cancer compared with people who do not. Animals that were given risperidone (the active substance in RISPERDAL) showed an increase in certain types of cancer (including tumours in the pituitary gland in the brain, tumours in the pancreas, or breast cancer). While this increased risk in animals has not been seen in humans receiving RISPERDAL, the risk cannot be totally ruled out.

Problems controlling body temperature

(Body temperature dysregulation)

Antipsychotic medicines may interfere with the body’s ability to reduce its inner temperature.

Special care with RISPERDAL is needed in patients who have problems controlling their body temperature or overheating. This could cause problems for patients who exercise hard, who are exposed to high heat, who are taking certain medicines, or who may become dehydrated.

These patients may have trouble cooling off or be more likely to become dehydrated.

It is unclear if antipsychotic drugs like RISPERDAL do have an effect on body temperature. Some studies suggest that problems with body temperature may be related to having schizophrenia, rather than taking medicine.

Suicide, suicide attempt, or thoughts of committing suicide

(Suicidality)

Suicide or thoughts of suicide are common in patients with schizophrenia.

High-risk patients (such as those with previous attempts or a history of substance abuse) should be closely supervised.

Feelings of depression in patients with bipolar disorder

(Depression in patients with affective disorders)

Patients taking RISPERDAL for manic episodes associated with bipolar disorder may be at risk of their symptoms switching from mania (where they may feel very excited, elated, agitated, enthusiastic, or hyperactive) to depression.


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Increased sensitivity toantipsychotics in patients who have Parkinson’s disease or a certain type of dementia

(Increased sensitivity to antipsychotics in patients with Parkinson’s disease and dementia with Lewy bodies)

Increased sensitivity to antipsychotics in patients with Parkinson’s disease and dementia with Lewy bodies is a side effect of atypical antipsychotic medicines, including RISPERDAL.

Special care with RISPERDAL is needed in patients with Parkinson’s disease or dementia. Parkinson’s disease may get worse with RISPERDAL treatment. Patients with Parkinson’s disease and dementia with Lewy bodies may be more likely to develop side effects of antipsychotic treatments like RISPERDAL, such asconfusion, movement problems, and unsteadiness when standing, which may lead to falls. These patients may also be at an increased risk of Neuroleptic Malignant Syndrome (see additional information above).

Special care is needed when using RISPERDAL along with medicines for Parkinson's disease (such as levodopa).

RISPERDAL has not been studied in patients with Parkinson’s disease or dementia with Lewy bodies.

Decrease in bone strength/fragile bones

(Decreased bone mineral density/Osteoporosis)

Osteoporosis may be a side effect of some atypical antipsychotic medicines, including RISPERDAL. It is thought that the high level of prolactin in the blood that is a side effect of some atypical antipsychotic medicines, including RISPERDAL, may cause the bones to become weaker over a long period of time. This needs to be studied more before any conclusions can be made.

Side effects when RISPERDAL treatment is changed to methylphenidate treatment in children

(Risperidone to methylphenidate “switch” reactions in children)

There have been a few reports of nervous system side effects when children treated with RISPERDAL were switched to treatment with methylphenidate. Although these few reports have not shown a clear risk, some experts suggest slowly decreasing the dose of RISPERDAL before stopping and then allowing patients a medication-free period before starting methylphenidate treatment.


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Effects on bone growth in adolescents

(Effects on skeletal growth)

Effects on bone growth, including delayed growth, were seen in animal studies with risperidone. In contrast, height in long-term open-label extension human trials of RISPERDAL were within expected values. However, the effect of long-term risperidone treatment on height has not been adequately studied. One small postmarketing observational study showed that risperidone-exposed children and adolescents were on average approximately 3.0 to 4.8 cm taller than those who received other atypical antipsychotics, but this study was not adequate to determine whether exposure to risperidone had any impact on final adult height, or whether the result was due to a direct effect of risperidone on bone growth, or the effect of the underlying disease itself on bone growth, or the result of better control of the underlying disease with resulting increase in linear growth. Since animal studies, human trials, and postmarketing studies have conflicting evidence, no trend can be concluded and this risk is considered "potential" and not "identified".

High levels of prolactin in the blood over time may affect growth and development in adolescents. Since high prolactin is a side effect of some atypical antipsychotic medicines, children and adolescents treated with RISPERDAL should be checked regularly by their doctor for effects on growth and development.

Effects on sexual development in adolescents

(Effects on puberty)

Effects on sexual development were seen in an animal study with risperidone, so this is considered a potential risk.

The effect of long-term treatment with RISPERDAL on sexual development has not been thoroughly studied.

High levels of prolactin in the blood over time may affect growth and development in adolescents. Since high prolactin is a side effect of some atypical antipsychotic medicines, children and adolescents treated with RISPERDAL should be checked regularly by their doctor for effects on growth and development.

Missing Information

Missing Information What is known

Use by patients with kidney problems, including those who need kidney dialysis (a treatment for people whose kidneys no longer work)

(Use in patients with renal impairment, including those who require haemodialysis)

RISPERDAL has not been systematically studied in patients with kidney problems, including those who need kidney dialysis.

Before taking RISPERDAL, patients should tell their doctors if they have kidney problems.

Doctors may give patients with kidney problems a lower than usual dose of RISPERDAL.


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Use by patients with liver problems

(Use in hepatic impairment)

RISPERDAL has not been systematically studied in patients with liver problems.

Before taking RISPERDAL, patients should tell their doctors if they have liver problems.

Doctors may give patients with liver problems a lower than usual dose of RISPERDAL.

Use by pregnant women

(Use during pregnancy)

RISPERDAL has not been studied in pregnant women.

Women should talk to their doctor before using RISPERDAL if they are pregnant or trying to become pregnant. The doctor will decide if RISPERDAL can be taken.

Newborn babies of mothers who have used RISPERDAL in the last trimester (last three months of their pregnancy) need to be watched carefully for side effects or withdrawal symptoms.

Use by breastfeeding women

(Use in nursing mothers)

RISPERDAL has not been studied in breastfeeding women.

RISPERDAL can pass into breast milk.

Women should talk to their doctor before using RISPERDAL if they are breastfeeding. The doctor will decide if RISPERDAL can be taken.

VI.2.5. Summary of Additional 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

safety risks and recommendations for minimising them. An abbreviated version of this in lay

language is provided in the form of the Patient Information Leaflet (PIL). The measures in these

documents are known as routine risk minimisation measures.

The SmPC and PIL for RISPERDAL are available nationally from the company that markets

RISPERDAL.

The company considers that the safety risks associated with this medicine can be managed with

the information in the SmPC and PIL, and therefore no special conditions or restrictions for its

safe and effective use (additional risk minimisation measures) have been proposed.


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VI.2.6. Planned Postauthorisation Development Plan

List of Studies in Postauthorisation Development Plan

Study/activity (including study number) Objectives

Safety concerns/efficacy issue addressed

Status (planned, started)

Date for submission of (interim and) final results

Study of breast cancer

To assess the effects of antipsychotics, including risperidone, on the rate of breast cancer

Relationship between breast cancer and antipsychotic medication exposure

Started Estimated: Dec 2015

Studies Which are a Condition of the Marketing Authorisation

The above study is not a condition of the marketing authorisation.

VI.2.7. Summary of Changes to the Risk Management Plan Over Time

Version Date Safety Concerns Comment

1.0 05 Dec 2013 Original version of the EU-RMP. None.

2.0 17 Jun 2014 Expanded the "use in haemodialysis patients" Missing Information safety concern to be "use in patients with renal impairment, including those receiving haemodialysis."

Added "use in hepatic impairment" as a Missing Information safety concern.

Harmonised the Important Potential Risk of "effects on skeletal growth" and the Important Identified Risk of "hyperprolactinaemia and potentially prolactin-related events" with more recent SmPCs.

Annex 2 (SmPCs and PILs) and Annex 12.2 (references) were updated; all other Annexes are the same as in the previous version.

PIL=Patient Information Leaflet; SmPC=Summary of Product Characteristics


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VI.2. Elements for a Public Summary

RISPERDAL CONSTA belongs to a group of medicines called atypical antipsychotics.

RISPERDAL CONSTA is used in adults to maintain the treatment of schizophrenia, where you

may see, hear, or feel things that are not there; believe things that are not true; or feel unusually

suspicious or confused.

RISPERDAL CONSTA is intended for patients who are currently treated with oral (e.g., tablets,

capsules) antipsychotics.

RISPERDAL CONSTA is given as an intramuscular injection either in the arm or buttock every

two weeks, administered by a health care professional.

VI.2.1. Overview of Disease Epidemiology

Schizophrenia is a disorder with symptoms such as hearing voices, seeing or sensing things that

are not there, mistaken beliefs, unusual suspiciousness, becoming withdrawn, incoherent speech,

and behaviour and emotional flatness. People with this disorder often may also feel depressed,

anxious, guilty, or tense.

The World Health Organisation estimates that there are 24 million people with schizophrenia

worldwide or approximately 1% of the general population. Schizophrenia usually appears in men

between 20 and 24 years of age and appears in women between 29 and 32 years of age.

Schizophrenia is more common in men than in women. Schizophrenia is a chronic disease and is

one of the leading causes of disability worldwide. People with schizophrenia are at increased risk

of having other health problems, including substance abuse, alcohol abuse and smoking.

VI.2.2. Summary of Treatment Benefits

The main treatment for schizophrenia is the use of antipsychotic medicines. Newer, atypical

antipsychotic medicines are usually preferred over older, typical antipsychotic medicines

because they have fewer side effects on the nervous system. In addition to the use of medicine,

psychosocial treatments such as therapy, work training, and life skills training are also important

in the long-term management of schizophrenia. Several atypical antipsychotics are available as

long-acting injections, which can be beneficial in patients who are not willing or able to stay on

treatment with oral medicines.

RISPERDAL CONSTA was approved in the EU based on the results of 3 main clinical trials in

patients with schizophrenia.

In 1 main short-term trial, RISPERDAL CONSTA was compared with placebo (a dummy treatment) in adults with schizophrenia. After 12 weeks of treatment, RISPERDAL CONSTA was useful in managing schizophrenia/schizoaffective disorder.

In a second short-term trial, RISPERDAL CONSTA was compared with RISPERDAL (tablet taken by mouth) in stable patients with schizophrenia. After 12 weeks of treatment, RISPERDAL CONSTA was as effective as RISPERDAL.


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In a main long-term trial in stable patients with schizophrenia or schizoaffective disorder, the effectiveness of RISPERDAL CONSTA was maintained for 50 weeks. The key measure showing benefit was the amount of change in symptoms on a standard scale for schizophrenia.

VI.2.3. Unknowns Relating to Treatment Benefits

There is either no or only limited information about the use of RISPERDAL CONSTA in

patients with kidney problems (including those who need dialysis [a treatment for people whose

kidneys no longer work]), patients with liver problems, pregnant women, and breastfeeding

women.


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VI.2.4. Summary of Safety Concerns

Important Identified Risks


High levels of a hormone called “prolactin” found on a blood test (Hyperprolactinaemia and potentially prolactin-related events)

RISPERDAL CONSTA as with other antipsychotic medicines that affect dopamine levels in the brain, can raise levels of a hormone called prolactin found on a blood test.

A high level of prolactin in the blood may or may not cause symptoms. When symptoms of high prolactin occur in men, they may include breast swelling, difficulty in getting or maintaining erections, other problems with sexual performance, or changes in the ability to produce children. In women, symptoms may include breast discomfort, leakage of milk from the breasts, missed menstrual periods, other problems with the menstrual cycle, or changes in the ability to produce children.

Special care with RISPERDAL CONSTA is needed in patients who already have an abnormally high level of the hormone prolactin in the blood before treatment or if they have a possible prolactin-dependent tumour (for example, a tumour in the pituitary gland in the brain). A doctor may order a blood test of prolactin for a patient who is experiencing symptoms that might be related to high levels ofprolactin. As with all medications, a patient’s doctor may decide to stop treatment with RISPERDAL if the risks are considered to outweigh the benefits in an individual patient. Apatient should not stop taking RISPERDAL without discussing this with the doctor who prescribed it.

An increase in time of contraction and relaxation of the heart ventricles found on an electrical tracing of heart activity

(QT prolongation)

QT prolongation was reported uncommonly, in 0.1% to 1% of patients taking RISPERDAL CONSTA.

There is a very small chance that this may lead to more serious heart problems, such as abnormal heart rhythms (‘arrhythmias’), particularly in patients with underlying heart problems that could increase their risk of death from such conditions.

Special care with RISPERDAL CONSTA is needed in patients with certain heart problems or other conditions that may increase the risk for QT prolongation, such as a family history of QT prolongation.

Special care is needed when using RISPERDAL CONSTA along with medicines that:

may change the electrical activity of the heart, such as medicines for malaria, heart rhythm problems, allergies (antihistamines), some antidepressants or other medicines for mental problems

cause a slow heart beat cause low blood potassium (such as

certain diuretics).


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Low blood pressure upon standing

(Orthostatic hypotension)

Orthostatic hypotension is a side effect of some atypical antipsychotic medicines, including RISPERDAL CONSTA.

Some people taking RISPERDAL CONSTA may feel faint, dizzy, or may pass out when they stand up or sit up suddenly.

Elderly patients are at a higher risk for orthostatic hypotension.

Special care with RISPERDAL CONSTA is needed in patients with certain heart problems. Examples include patients with an irregular heart rhythm, patients prone to low blood pressure, or patients using medicines to treat raised blood pressure. RISPERDAL CONSTA may cause low blood pressure. The dose may need to be adjusted.

Slow or impaired movement or uncontrollable muscle movements

(Extrapyramidal symptoms/tardive dyskinesia)

Extrapyramidal symptoms/tardive dyskinesia are side effects of atypical antipsychotic medicines, including RISPERDAL CONSTA.

Extrapyramidal symptoms may include a sensation of stiffness or tightness of the muscles, a slow shuffling walk, a loss of expression on the face, restlessness, abnormal movements of the eyes, mouth, tongue, or jaw, and repetitive, spastic, or writhing movements.

Some extrapyramidal symptoms were reported in 1 to 10% of patients taking RISPERDAL CONSTA, while other extrapyramidal symptoms were reported in more than 10% of patients taking RISPERDAL CONSTA.

There is also a small risk (between 0.1% and 1% of patients taking RISPERDAL CONSTA) of a more serious movement disorder called tardive dyskinesia, which involves uncontrollable twitching or jerkingmovements in the face, tongue, or other parts of the body.

RISPERDAL CONSTA should be used carefully in patients who have experienced movement problems in the past, including Parkinson’s disease or dementia with Lewy bodies.Special care with RISPERDAL CONSTA is needed in patients who have ever experienced involuntary movements of the tongue, mouth, and face.A patient needs to tell his/her doctor immediately if he/she experiences involuntary rhythmic movements of the tongue, mouth, and face. Withdrawal of RISPERDALCONSTA may be needed.In patients who require long-term treatment, the aim is to control symptoms with the smallest dose and the shortest duration of treatment.


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A condition with symptoms that include high temperature, muscle stiffness, sweating, or a lowered level of consciousness

(Neuroleptic malignant syndrome)

Neuroleptic malignant syndrome is a rare but serious side effect that could be fatal and has been reported with RISPERDAL CONSTA and similar medicines. Neuroleptic malignant syndrome occurs rarely (in 0.01% to 0.1% of patients taking RISPERDAL CONSTA).

Special care with RISPERDAL CONSTA is needed in patients who have ever had Neuroleptic malignant syndrome.Patients need to tell their doctor immediately if they experience fever, muscle stiffness, shaking, sweating more than usual, increased heart rate or blood pressure, or muscle pain or weakness, confusion, or a lowered level of consciousness. Immediate medical treatment may be needed.All antipsychotics should be discontinued if a patient develops signs or symptoms of Neuroleptic malignant syndrome.

Diabetes or problems due to a high blood sugar level

(Diabetes mellitus and hyperglycaemia-related adverse events)

Diabetes mellitus or worsening of pre-existing diabetes mellitus have been seen with patients taking RISPERDAL CONSTA.

With RISPERDAL CONSTA, high blood sugar was observed in 1% to 10% of patients and diabetes in 0.1% to 1% of patients. Risk factors for diabetes include being overweight or having a family history of diabetes.

Patients treated with RISPERDAL CONSTA should be checked by their doctor for signs of high blood sugar. Special care with RISPERDAL CONSTA is needed in patients with diabetes and blood glucose should be monitored regularly in these patients.In patients at increased risk of cardiovascular disease, blood glucose should be monitored regularly.

An increase in body weight

(Weight gain)

Significant weight gain may adversely affect health.

Patients with schizophrenia may be at higher risk for weight gain due to poor dietary choices and decreased levels of physical activity. Weight gain was reported in 1% to 10% of patients taking RISPERDAL CONSTA.

Before RISPERDAL CONSTA treatment is started, body weight should be measured and it should be regularly monitored during treatment.By monitoring body weight, especially in patients at increased risk of cardiovascular disease or diabetes mellitus. Lifestyle measures (such as change in diet and increase in exercise) should be considered early if patients experience significant weight gain.


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Convulsion (fits)

(Seizures)

Convulsions were reported uncommonly, in 0.1% to 1% of patients taking RISPERDAL CONSTA.

Special care with RISPERDAL CONSTA is needed in patients with epilepsy, in patients who have ever had seizures, or in patients with an increased risk for seizures.

Feeling sleepy or less alert

(Somnolence)

Feeling sleepy or less alert was reported in 1 to 10% of patients taking RISPERDAL CONSTA.

This may affect the ability to drive a car, operate machines, or do other things that require alertness. These problems are more likely to happen if RISPERDAL CONSTA taken in combination with other medicines (or alcohol) that work in the brain.

Special care is needed when using RISPERDAL CONSTA along with medicines that work on the brain to help patients calm down such as (benzodiazepines) or some medicines for pain (opiates), medicines for allergy (some antihistamines), as RISPERDAL CONSTA may increase the sedative effect of all of these.

Special care is needed when using RISPERDAL CONSTA along with alcohol, as RISPERDAL CONSTA may increase its sedative effect.

Since tiredness may occur during treatment with RISPERDAL CONSTA, patients should not drive or use any tools or machines without talking to their doctor first.

A prolonged or painful erection(Priapism)

Priapism was reported rarely, in 0.01% to 0.1% of patients taking RISPERDAL CONSTA.

Special care with RISPERDAL CONSTA is needed in men who have ever had a prolonged or painful erection.

Men treated with RISPERDAL CONSTA need to tell their doctor immediately if they experience a prolonged or painful erection. Immediate medical treatment may be needed.


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Stroke or “mini” stroke

(Cerebrovascular accident)

It is not known how often strokes occur in patients with schizophrenia who do not receive treatment.

Sudden loss of blood supply to the brain (stroke or "mini" stroke) was reported uncommonly, in 0.1% to 1% of patients taking RISPERDAL CONSTA.

Blood vessel problems in the brain were reported rarely, in 0.01% to 0.1% of patients taking RISPERDAL CONSTA.

Special care with RISPERDAL CONSTA is needed in patients with any factors which would favour having a stroke, such as high blood pressure, cardiovascular disorder, or circulation disorders of the brain.

RISPERDAL CONSTA is not for use in elderly patients with dementia.

Medical treatment should be sought straight away if a patient or caregiver notices a sudden change in mental state or sudden weakness or numbness of the face, arms or legs, especially on one side, or slurred speech, or speech or vision problems, even for a short period of time. These may be signs of a stroke.

Blood clots in the veins, typically in the legs (“DVT”). In some cases (i.e., a venous thromboembolism), these clots may travel to the lungs

(Venous thromboembolism)

With RISPERDAL CONSTA, blood clots in veins and lungs have been reported rarely, in 0.01% to 0.1% of patients.

Special care with RISPERDAL CONSTA is needed if a patient or someone else in their family has a history of blood clots.

Patients should seek medical advice immediately if they experience blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness in the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty breathing.

White blood cell count decreased

(Leukopenia)

Low numbers of a certain type of white blood cell needed to protect the body against infection have been reported with RISPERDAL CONSTA.

Special care with RISPERDAL CONSTA is needed in patients who have had low levels of white blood cells in the past (which may or may not have been caused by other medicines). White blood counts should be monitored.

A patient’s doctor may decide to stop RISPERDAL CONSTA treatment if there is a serious decrease in white blood cells without a known cause.


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A dangerously low number of a certain type of white blood cell needed to fight infection

(Agranulocytosis)

With RISPERDAL CONSTA, agranulocytosis has been reported rarely, in 0.01% to 0.1% of patients

Special care with RISPERDAL CONSTA is needed in patients who have had low levels of white blood cells in the past (which may or may not have been caused by other medicines). White blood counts should be monitored.

Patients should be carefully monitored for fever or other symptoms of infection and treated promptly.

For serious cases, a patient’s doctor should stop RISPERDAL CONSTA treatment and monitor white blood cell counts until the patient recovers.

A decrease in platelets, the type of blood cell that helps stop bleeding

(Thrombocytopenia)

A decrease in platelets was reported in 0.1% to 1% of patients taking RISPERDAL CONSTA. Often, decreased platelet levels do not cause problems, but can increase the risk of bruising, nosebleeds and/or bleeding gums. Patients with low platelets may also feel more weak and tired than usual.

Platelet counts and symptoms can be monitored during treatment with RISPERDAL CONSTA.

In most cases when this condition is caused by a medicine, stopping the medicine leads to recovery.

Breakdown of muscle fibres and pain in muscles

(Rhabdomyolysis)

This condition was reported rarely (in 0.01% to 0.1% of patients taking RISPERDAL CONSTA).

If rhabdomyolysis occurs, a patient’s doctor should stop all antipsychotic medications, including RISPERDAL CONSTA.

By monitoring for early symptoms. If a patient develops signs or symptoms indicative of Neuroleptic Malignant Syndrome, including rhabdomyolysis,all antipsychotics should be discontinued.

Increased risk of death in elderly patients with dementia

(Overall increased mortality in elderly patients with dementia)

Increased risk of death in elderly patients with dementia is a safety concern with some atypical antipsychotic medicines.



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Stroke or “mini” stroke in elderly patients with dementia

(Cerebrovascular adverse events in elderly patients with dementia)

Stroke or “mini” stroke in elderly patients with dementia is a safety concern with some atypical antipsychotic medicines.


Important Potential Risks


Cancer of the pituitary gland, pancreas, or breast

(Carcinogenicity [pituitary adenomas; endocrine pancreas tumours; breast cancer])

Information gathered with RISPERDAL CONSTA and similar medicines has not shown that people who take them are at any increased risk of developing cancer compared with people who do not. Animals that were given risperidone (the active substance in RISPERDAL CONSTA) showed an increase in certain types of cancer (including tumours in the pituitary gland in the brain, tumours in the pancreas, or breast cancer). While this increased risk in animals has not been seen in humans receiving RISPERDAL CONSTA, the risk cannot be totally ruled out.

Problems controlling body temperature

(Body temperature dysregulation)

Antipsychotic medicines may interfere with the body’s ability toreduce its inner temperature.

Special care with RISPERDAL CONSTA is needed in patients who have problems controlling their body temperature or overheating. This could cause problems for patients who exercise hard, who are exposed to high heat, who are taking certain medicines, or who may become dehydrated.

These patients may have trouble cooling off or be more likely to become dehydrated.

It is unclear if antipsychotic drugs like RISPERDAL CONSTA do have an effect on body temperature. Some studies suggest that problems with body temperature may be related to having schizophrenia, rather than taking medicine.

Suicide, suicide attempt, or thoughts of committing suicide

(Suicidality)

Suicide or thoughts of suicide are common in patients with schizophrenia.

High-risk patients (such as those with previous attempts or a history of substance abuse) should be closely supervised.


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Feelings of depression in patients with bipolar disorder

(Depression in patients with affective disorders)

Patients taking RISPERDAL for manic episodes associated with bipolar disorder may be at risk of their symptoms switching from mania (where they may feel very excited, elated, agitated, enthusiastic, or hyperactive) to depression.

RISPERDAL CONSTA is not approved for use in patients with bipolar disorder.

Increased sensitivity to antipsychotics in patients who have Parkinson’s disease or a certain type of dementia

(Increased sensitivity to antipsychotics in patients with Parkinson’s disease and dementia with Lewy bodies)

Increased sensitivity to antipsychotics in patients with Parkinson’s disease and dementia with Lewy bodies is a side effect of atypical antipsychotic medicines, including RISPERDAL CONSTA.

RISPERDAL CONSTA is not for use in elderly patients with dementia. Special care with RISPERDAL CONSTA is needed in patients with Parkinson’s disease. Parkinson’s disease may get worse with RISPERDAL CONSTA treatment. Patients with Parkinson’s disease and dementia with Lewy bodies may be more likely to develop side effects of antipsychotic treatments like RISPERDAL CONSTA, such as confusion, movement problems, and unsteadiness when standing, which may lead to falls. These patients may also be at an increased risk of Neuroleptic Malignant Syndrome (see additional information above).

Special care is needed when using RISPERDAL CONSTA along with medicines for Parkinson's disease (such as levodopa).

RISPERDAL CONSTA has not been studied in patients with Parkinson’s disease or dementia with Lewy bodies.

Decrease in bone strength/fragilebones

(Decreased bone mineral density/Osteoporosis)

Osteoporosis may be a side effect of some atypical antipsychotic medicines, including RISPERDAL CONSTA. It is thought that the high level of prolactin in the blood that is a side effect of some atypical antipsychotic medicines, including RISPERDAL CONSTA, may cause the bones to become weaker over a long period of time. This needs to be studied more before any conclusions can be made.

Side effects when RISPERDAL treatment is changed to methylphenidate treatment in children

(Risperidone to methylphenidate “switch” reactions in children)

There have been a few reports of nervous system side effects when children treated with RISPERDAL were switched to treatment with methylphenidate.

RISPERDAL CONSTA is not for use in children and adolescents.


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Effects on bone growth in adolescents

(Effects on skeletal growth)

Effects on bone growth, including delayed growth, were seen in animal studies with risperidone. In contrast, height in long-term open-label extension human trials of oral RISPERDAL were within expected values. However, the effect of long-term risperidone treatment on height has not been adequately studied. One small postmarketing observational study showed that children and adolescents exposed to oral risperidone were on average approximately 3.0 to 4.8 cm taller than those who received other atypical antipsychotics, but this study was not adequate to determine whether exposure to oral risperidone had any impact on final adult height, or whether the result was due to a direct effect of oral risperidone on bone growth, or the effect of the underlying disease itself on bone growth, or the result of better control of the underlying disease with resulting increase in linear growth. Since animal studies, human trials, and postmarketing studies have conflicting evidence, no trend can be concluded and this risk is considered "potential" and not "identified".


Effects on sexual development in adolescents

(Effects on puberty)

Effects on sexual development were seen in an animal study with risperidone, so this is considered a potential risk.


Missing Information


Use by patients with kidney problems, including those who need kidney dialysis (a treatment for people whose kidneys no longer work)

(Use in patients with renal impairment, including those who require haemodialysis)

RISPERDAL CONSTA has not been systematically studied in patients with kidney problems, including those who need kidney dialysis.

Before taking RISPERDAL CONSTA, patients should tell their doctors if they have kidney problems.

For patients with kidney problems, doctors may give lower than usual doses of oral RISPERDAL to test whether starting RISPERDAL CONSTA treatment is expected to be tolerable.

Use by patients with liver problems

(Use in hepatic impairment)

RISPERDAL CONSTA has not been systematically studied in patients with liver problems.

Before taking RISPERDAL CONSTA, patients should tell their doctors if they have liver problems.

For patients with liver problems, doctors may give lower than usual doses of oral RISPERDAL to test whether starting RISPERDAL CONSTA treatment is expected to be tolerable.


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Use by pregnant women

(Use during pregnancy)

RISPERDAL CONSTA has not been studied in pregnant women.

Women should talk to their doctor before using RISPERDAL CONSTA if they are pregnant or trying to become pregnant. The doctor will decide if RISPERDAL CONSTA can be taken.

Newborn babies of mothers who have used RISPERDAL CONSTA in the last trimester (last three months of their pregnancy) need to be watched carefully for side effects or withdrawal symptoms.

Use by breastfeeding women

(Use in nursing mothers)

RISPERDAL CONSTA has not been studied in breastfeeding women.

RISPERDAL CONSTA can pass into breast milk.

Women should talk to their doctor before using RISPERDAL CONSTA if they are breastfeeding. The doctor will decide if RISPERDAL CONSTA can be taken.

VI.2.5. Summary of Additional 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

safety risks and recommendations for minimising them. An abbreviated version of this in lay

language is provided in the form of the Patient Information Leaflet (PIL). The measures in these

documents are known as routine risk minimisation measures.

The SmPC and PIL for RISPERDAL CONSTA are available nationally from the company that

markets RISPERDAL CONSTA.

The company considers that the safety risks associated with this medicine can be managed with

the information in the SmPC and PIL, and therefore no special conditions or restrictions for its

safe and effective use (additional risk minimisation measures) have been proposed.

VI.2.6. Planned Postauthorisation Development Plan

List of Studies in Postauthorisation Development Plan

Study/activity (including study number) Objectives

Safety concerns/efficacy issue addressed

Status (planned, started)

Date for submission of (interim and) final results

Study of breast cancer

To assess the effects of antipsychotics, including risperidone, on the rate of breast cancer

Relationship between breast cancer and antipsychotic medication exposure

Started Estimated: Dec 2015


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Studies Which Are a Condition of the Marketing Authorisation

The above study is not a condition of the marketing authorization.

VI.2.7. Summary of Changes to the Risk Management Plan Over Time

Version Date Safety Concerns Comment

1.0 05 Dec 2013 Original version of the EU-RMP. None.

2.0 17 Jun 2014 Expanded the "use in haemodialysis patients" Missing Information safety concern to be "use in patients with renal impairment, including those receiving haemodialysis."

Added "use in hepatic impairment" as a Missing Information safety concern.

Harmonised the Important Potential Risk of "effects on skeletal growth" and the Important Identified Risk of "hyperprolactinaemia and potentially prolactin-related events" with more recent SmPCs.

Annex 2 (SmPCs and PILs) and Annex 12.2 (references) were updated; all other Annexes are the same as in the previous version.

PIL=Patient Information Leaflet; SmPC=Summary of Product Characteristics

Documents

VI.2. Elements for a Public Summary RISPERDAL belongs to a ... · RISPERDAL improved the symptoms of dementia compared with placebo in 3 short-term trials in 1,150 elderly adults