Consumer medicine information

Risvan

Risperidone

BRAND INFORMATION

Brand name

Risvan

Active ingredient

Risperidone

Schedule

SUMMARY CMI

RISVAN^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using RISVAN?

RISVAN contains the active ingredient risperidone which belongs to the group of medicines called "antipsychotics".

RISVAN is used to treat schizophrenia in adult patients.

For more information, see Section 1. Why am I using RISVAN? in the full CMI.

2. What should I know before I use RISVAN?

Do not use RISVAN if you have ever had an allergic reaction to risperidone or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use RISVAN? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with RISVAN and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use RISVAN?

The information for your doctor or nurse on the right way to reconstitute RISVAN is included in the package.
Your doctor or healthcare provider will give you the injection with a single use device in the arm or buttock.
Injection is not to be given intravenously.

More instructions can be found in Section 4. How do I use RISVAN? in the full CMI.

5. What should I know while using RISVAN?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using RISVAN.
Things you should not do	Do not stop using this medicine suddenly
Driving or using machines	Do not drive or use any tools or machines without talking to your doctor first. Dizziness, tiredness, and vision problems may occur during treatment with RISVAN.
Drinking alcohol	You should avoid drinking alcohol when using RISVAN.
Looking after your medicine	Do not store above 25°C. Store in the original package in order to protect from moisture. Use RISVAN immediately after reconstitution.

For more information, see Section 5. What should I know while using RISVAN? in the full CMI.

6. Are there any side effects?

The most serious side effects that may occur are tardive dyskinesia (twitching or jerking movements that you cannot control in your face, tongue, or other parts of your body); blood clots in the veins, especially in the legs (symptoms include swelling, pain and redness in the leg); fever, muscle stiffness, sweating or a lowered level of consciousness; prolonged or painful erection; severe allergic reaction characterized by fever, swollen mouth, face, lip or tongue, shortness of breath, itching, skin rash or drop in blood pressure (anaphylactic reaction or angioedema); dark red or brown urine or notable decreased urination with muscle weakness or trouble moving arms and legs (signs of rhabdomyolysis); weakness or lightheadedness, fever, chills, or sores in the mouth. The most common side effects are difficulty falling or staying asleep; movement disorders that may include slow or impaired movements, sensation of stiffness or tightness of the muscles, a slow shuffling walk, tremor while at rest, increased saliva and/or drooling, and a loss of expression on the face (signs of Parkinsonism); headache.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

RISVAN^®

Active ingredient(s): risperidone

Consumer Medicine Information (CMI)

This leaflet provides important information about using RISVAN. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using RISVAN.

Where to find information in this leaflet:

1. Why am I using RISVAN?
2. What should I know before I use RISVAN?
3. What if I am taking other medicines?
4. How do I use RISVAN?
5. What should I know while using RISVAN?
6. Are there any side effects?
7. Product details

1. Why am I using RISVAN?

RISVAN contains the active ingredient risperidone which belongs to the group of medicines called ‘antipsychotics’.

RISVAN is used in adult patients to treat 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.

RISVAN is intended for patients who show tolerability and effectiveness to oral (e.g., tablets) risperidone.

RISVAN can help alleviate the symptoms of your condition and stop your symptoms from coming back.

2. What should I know before I use RISVAN?

Warnings

Do not use RISVAN if:

You are allergic (hypersensitive) to risperidone, or any of the other ingredients of this medicine listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

Are prone to dizziness when standing up or lying from sitting position.
Have a heart problem. Examples include an irregular heart rhythm or if you are using medicines for your high blood pressure. RISVAN may cause low blood pressure. Your dose may need to be adjusted.
Know of any factors which would favour you having a stroke, such as high blood pressure, cardiovascular disorder or blood vessel problems in the brain.
Have ever experienced involuntary movements of the tongue, mouth and face.
Have ever had a condition whose symptoms include high temperature, muscle stiffness, sweating or a lowered level of consciousness (also known as Neuroleptic Malignant Syndrome).
Have Parkinson's disease.
Have dementia.
Know that you have had low levels of white blood cells in the past (which may or may not have been caused by other medicines).
Are diabetic.
Have epilepsy.
Are a man and you have ever had a prolonged or painful erection.
Have problems controlling your body temperature or overheating.
Have kidney problems.
Have liver problems.
Have an abnormally high level of the hormone; prolactin in your blood or if you have a tumour, which is possibly dependent on prolactin.
Or someone else in your family has a history of blood clots, as antipsychotics have been associated with formation of blood clots.

Dangerously low numbers of a certain type of white blood cell needed to fight infection in your blood has been seen very rarely with patients taking risperidone. Your doctor may therefore check your white blood cell counts before and during treatment.

Even if you have previously tolerated oral risperidone, rarely allergic reactions occur after receiving injections of RISVAN. Seek medical attention right away if you experience a rash, swelling of your throat, itching, or breathing problems as these may be signs of a serious allergic reaction.

RISVAN may cause you to gain weight. Significant weight gain may adversely affect your health. Your doctor should regularly measure your body weight.

Diabetes mellitus or worsening of pre-existing diabetes mellitus have been seen with patients taking RISVAN. Your doctor should therefore check for signs of high blood sugar. In patients with pre-existing diabetes mellitus blood glucose should be monitored regularly.

RISVAN commonly raises levels of a hormone called "prolactin". This may cause side effects such as menstrual disorders or fertility problems in women, breast swelling in men (see section 6: Are there any side effects?). If such side effects occur, evaluation of the prolactin level in the blood is recommended.

During an operation on the eye for cloudiness of the lens (cataract), problems may arise that may lead to eye damage. If you are planning to have an operation on your eye, make sure you tell your eye doctor that you are taking this medicine.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your doctor will decide if you can use it.

The following symptoms may occur in newborn babies, of mothers that have used risperidone in the last trimester (last three months of their pregnancy): shaking, muscle stiffness, and/or weakness, sleepiness, agitation, breathing problems, and difficulty in feeding. If your baby develops any of these symptoms, you may need to contact your doctor.

As RISVAN is excreted in breast milk, it is recommended that you do not breastfeed while using this medicine.

RISVAN can raise your levels of a hormone called "prolactin" that may impact fertility (see section 6: Are there any side effects?).

Elderly

RISVAN should be used with caution in elderly. RISVAN is NOT indicated in elderly people with dementia.

Children and adolescents

Do not give this medicine to children and adolescents under 18 years old.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins, or supplements that you buy without a prescription from your pharmacy, supermarket, or health food shop.

Some medicines may interfere with RISVAN and affect how it works.

It is especially important to talk to your doctor or pharmacist if you are taking any of the following:

Medicines that work on your brain such as to help you calm down (benzodiazepines) or some medicines for pain (opiates), medicines for allergy (some antihistamines), as RISVAN may increase the sedative effect of all of these.
Medicines that may change the electrical activity of your heart, such as medicines for malaria, heart rhythm problems, allergies (antihistamines), some antidepressants or other medicines for mental problems.
Medicines that cause a slow heartbeat.
Medicines that cause low blood potassium (such as certain diuretics).
Medicines to treat raised blood pressure. RISVAN can lower blood pressure
Medicines for Parkinson's disease (such as levodopa).
Medicines that increase the activity of the central nervous system (psychostimulants, such as methylphenidate).
Medicines used for heart problems or swelling of parts of your body due to accumulation of too much fluid - water tablets (diuretics, such as furosemide or chlorothiazide). RISVAN taken by itself or with furosemide, may have an increased risk of stroke or death in elderly people with dementia.

Medicines that may increase the effect of RISVAN include:

Medicines used to treat certain types of heart disease (quinidine, disopyramide, procainamide, propafenone, amiodarone, sotalol).
Medicines used to treat depression and other psychiatric disorders (paroxetine, sertraline fluoxetine, fluvoxamine and tricyclic antidepressants)
Medicines used to treat high blood pressure (beta-blockers).
Medicines used to treat psychosis or to calm down (phenothiazines).
Medicine blockers used to treat of the acidity of stomach (cimetidine, ranitidine).
Medicines used to treat fungal infections (itraconazole and ketoconazole).
Certain medicines used to treat HIV/AIDS, such as ritonavir.

If you start or stop taking such medicines, you may need a different dose of risperidone.

Medicines that may reduce the effect of RISVAN include:

Medicine for treating some infections (rifampicin)
Medicines used to treat epilepsy {carbamazepine, phenytoin, phenobarbital)

If you start or stop taking such medicines, you may need a different dose of risperidone.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect RISVAN.

4. How do I use RISVAN?

How much to use

RISVAN will be given to you by injection by a healthcare professional. It is a medicine designed to gradually release the active ingredient in your body so that you do not have to take this medicine every day.
You will be given RISVAN as an intramuscular injection either in the upper arm or buttock every 28 days, by a healthcare professional. Injections should be alternated between the right and left sides.

When to use RISVAN

The recommended dose is 75 mg every 28 days, but a higher dose of 100 mg every 28 days may be necessary. Your doctor will decide on the dose of RISVAN that is right for you.

How to use RISVAN powder and diluent for prolonged-release suspension for injection

If you are currently treated with other antipsychotics than risperidone, but have taken risperidone in the past, you should begin taking oral risperidone with at least 6 days before beginning treatment with RISVAN.
If you have never taken any form of risperidone, you should begin taking oral risperidone with at least 14 days before beginning treatment with RISVAN. The duration of the oral risperidone period will be determined by your physician.

People with kidney problems

RISVAN is not recommended in patients with moderate to severe impaired kidney function.

If you forget to use RISVAN

If you think that you did not receive a dose, you should contact your doctor or another healthcare provider immediately.

If you use too much RISVAN

If you think that you have used too much RISVAN, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using RISVAN?

Things you should do

It is important not to miss your appointments when you are supposed to receive your injections of this medicine once every 28 days. If you cannot keep your appointment, make sure to contact your doctor right away to discuss another date when you can come in for your injection.

Call your doctor straight away if you:

If you think that the symptoms of your disease condition are coming back.

Remind any doctor, dentist or pharmacist you visit that you are using RISVAN.

Be careful during strenuous exercise or exposure to extreme heat. Try to drink plenty of water.

Things you should not do

Do not stop using this medicine suddenly.
If you stop using RISVAN, you will lose the effects of the medicine. You should not stop using this medicine unless told to do so by your doctor as your symptoms may return.

Driving or using machines

Do not drive or use any tools or machines without talking to your doctor first.

Dizziness, tiredness, and vision problems may occur during treatment with RISVAN.

Drinking alcohol

You should avoid drinking alcohol when using RISVAN.

Alcohol may worsen the symptoms of your condition.

Looking after your medicine

RISVAN will be stored by your doctor or pharmacist. The injection is to be kept in the original package and in a cool dry place, where the temperature stays below 25°C.
Your doctor or pharmacist will not use it beyond the expiry date (month and year) printed on the pack. Medicines cannot be stored indefinitely, even if stored properly.
RISVAN will be given to you by your doctor immediately after reconstitution.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Serious side effects

Serious side effects

What to do

Head and neurology related:

Tardive Dyskinesia - experiencing involuntary rhythmic movements, twitching or jerking movements that you cannot control in your face, tongue, or other parts of your body.
Experience fever, muscle stiffness, sweating or a lowered level of consciousness (a disorder called "Neuroleptic Malignant Syndrome").
Dizziness
Tremor (shaking)
Brain ischemia (insufficient blood flow to the brain)
Unresponsive to stimuli, loss of consciousness, low level of consciousness
Convulsion (fits), fainting
Blood vessel problems in the brain
Coma due to uncontrolled diabetes

Blood clots related:

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.

Reproductive system related:

If you are a man and experience prolonged or painful erection. This is called priapism.

Allergy related:

Experience severe allergic reaction characterized by fever, swollen mouth, face, lip or tongue, shortness of breath, itching, skin rash or drop in blood pressure (anaphylactic reaction or angioedema). You may experience severe allergic reactions to RISVAN even if you were not allergic to risperidone tablets.

Muscles and joints related:

You have a dark red or brown urine or notable decreased urination along with muscle weakness or trouble moving arms and legs. These may be signs of rhabdomyolysis (a rapid damage of your muscles).

Blood related:

You have weakness or lightheadedness, fever, chills, or sores in the mouth. These may be signs of very low number of granulocytes (a type of white blood cell to help you against infection).

Immediately visit the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Less Serious Side Effects

Other side effects

What to do

Mental system related:

Difficulty falling or staying asleep.
Sleep disorder
Irritability
Depression
Anxiety
Feeling sleepy, or less alert
Mania (elated mood)
Confusion
Decreased sexual drive
Nervousness
Nightmares.
Sleep walking.
Sleep-related eating disorder.
Lack of emotion, inability to reach orgasm.

Head and neurology related:

Parkinsonism: movement disorders that slow or impaired movements, sensation of stiffness or tightness of the muscles, and sometimes even a sensation of movement "freezing up" and then restarting. Other signs include a slow shuffling walk, a tremor while at rest, increased saliva and/or drooling, and a loss of expression on the face.
Headache.
Dystonia, which is slow or sustained involuntary contraction of muscles which can involve any part of the body and may result in abnormal posture
Dyskinesia, which can be repetitive, spastic, writhing movements, or twitching movements of the involuntary muscles
Akathisia, which is inability to stay still.
A restless urge to move parts of your body, balance disorder, abnormal coordination, dizziness upon standing, poor attention, problems with speech, loss or abnormal sense of taste, reduced sensation of skin to pain and touch, a sensation of tingling, pricking, or numbness on the skin.
Involuntary shaking of the head.

Infections related:

Pneumonia (lung infection), bronchitis (infection of the main airways of the lungs), sinus infection, urinary tract infection, ear infection, flu, flu-like symptoms, sore throat, cough, stuffy nose, fever, eye infection or "pink eye"
Bladder infection, tonsillitis, fungal infection of nails, infection of the deeper layers of skin, viral infection, inflammation of the skin caused by mites.

Blood related:

Decrease or increase in white blood cells in your blood
Decrease in platelets (blood cells that help you stop bleeding)
Anemia or decrease in red blood cells
Increase in blood creatine phosphokinase enzyme
Increased liver enzymes which can cause changes in liver function tests that your doctor may ask to be done.

Allergy related:

Allergic reaction.

Hormones and metabolism related:

Raised levels of a hormone called "prolactin" found in a blood test. Symptoms of high prolactin occur uncommonly and may include in men breast swelling, difficulty in getting or maintaining erections, decreased sexual desire.
Weight gain, increased or decreased appetite.
Inappropriate secretion of a hormone that controls urine volume.
Excess of sugar in the urine, low blood sugar.
Dangerously excessive intake of water.
Increased insulin (a hormone that controls blood sugar levels) in your blood.

Eye related:

Blurry vision.
Oversensitivity of the eyes to light, dry eye, increased tears, redness of the eyes.
Glaucoma (increased pressure within the eye), problems with movement of your eyes, eye rolling, eyelid margin crusting/inflammation.
Eye problems during cataract surgery.

Ear related:

Sensation of spinning (vertigo), ringing in the ears, ear pain.

Heart and blood vessels related:

Irregular and often rapid heart rate, slow heart rate, abnormal electrocardiogram (test that measures the electrical activity of the heartbeat), palpitations (a fluttering or pounding feeling in your chest)
Low blood pressure, drop in blood pressure after standing, flushing.

Lung related:

Congestion of breathing passages, wheezing (coarse/whistling sound during breathing), nose bleeds.
Trouble breathing during sleep (sleep apnea), fast, shallow breathing.
Lung infection caused by inhaling food into the breathing passages, lung congestion, breathing passage disorder, voice disorder, crackly lung sounds.

Gastrointestinal related:

Abdominal pain, abdominal discomfort, vomiting, nausea, constipation, diarrhea, indigestion, dry mouth, toothache.
Stomach or intestinal infection or irritation, fecal incontinence, difficulty swallowing, excessive passing of gas or wind.
Inflammation of the pancreas, a blockage in the bowels.
Swollen tongue, chapped lips.
Lack of bowel muscle movement that causes blockage.

Liver related:

Jaundice (yellowing of the skin and the eyes).

Skin related:

Rash, skin redness.
Hives, thickening of skin, skin disorder, intense itching of the skin, hair loss, eczema (patches of skin become inflamed, itchy, cracked, and rough), dry skin, skin discoloration, acne, seborrheic dermatitis (red, scaly, greasy, itchy, and inflamed skin), skin lesion.
Dandruff.
Hardening of the skin

Muscles and joints related:

Muscle spasms, bone or muscle pain, back pain, joint pain.
Abnormal posture, joint stiffness, joint swelling, muscle weakness, neck pain, walking abnormality, thirst, feeling unwell, chest discomfort or general discomfort, feeling "out of sorts".

Urinary related:

Incontinence (involuntary leakage of urine).
Frequent passing of urine, inability to pass urine, pain when passing urine.

Reproductive system related:

Erectile dysfunction, ejaculation disorder, development of breast in men.
Loss of menstrual periods or other problems with your cycle (females).
Lack of ovulation
Fertility problems
Leakage of milk from the breasts, sexual dysfunction, breast pain or discomfort, vaginal discharge.
Breast enlargement, breast engorgement (hard, swollen, painful breasts from too much breast milk production).

General disorders related:

Swelling of the body, arms or legs, chest pain, lack of energy and strength, fatigue, pain.
Chills.
Feeling thirsty, feeling unwell, chest discomfort, feeling "out of sorts", general discomfort
Decreased body temperature, coldness in arms and legs.
Symptoms of drug withdrawal (also in newborns).

Injection site related:

A reaction at the injection site, including discomfort, pain, redness or swelling.
Fall.
Procedural pain.

Contact your doctor if you experience any of the side effects listed in this table.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What RISVAN contains

Active ingredient (main ingredient)	risperidone
Other ingredients (inactive ingredients)	Pre-filled syringe of powder: polyglactin. Pre-filled syringe of diluent: dimethyl sulfone

Do not take this medicine if you are allergic to any of these ingredients.

What RISVAN looks like

Each kit box of RISVAN powder and diluent for prolonged-release suspension for injection contains:

An aluminium pouch with one pre-filled syringe containing powder (within this powder is the active ingredient, risperidone) and a silica gel desiccant sachet. The powder is white to white-yellowish, non-aggregated.
An aluminium pouch with one pre-filled syringe containing the diluent and a silica gel desiccant sachet. The pre-filled syringe of the diluent contains a clear solution and has a red (RISVAN 75 mg, AUST R 377801) or a blue (RISVAN 100 mg, AUST R 388583) finger flange.
One sterile needle for IM injection 2 inch (0.90 x 51mm [20G]) with safety shield used for gluteus administration.
One sterile needle for IM injection 1 inch (0.80 x 25mm [21G]) with safety shield used for deltoid administration.

RISVAN is registered on the Australian Register of Therapeutic Goods. Australian Register Numbers:

RISVAN 75 mg: AUST R 377801

RISVAN 100 mg: AUST R 388583

Who distributes RISVAN

Servier Laboratories (Aust.) Pty. Ltd.
www.servier.com.au
Level 4, Building 9
588A Swan Street
Burnley, 3121, Victoria

This leaflet was prepared in July 2024

Published by MIMS February 2025

BRAND INFORMATION

Brand name

Risvan

Active ingredient

Risperidone

Schedule

1 Name of Medicine

Risperidone.

2 Qualitative and Quantitative Composition

Risvan 75 mg powder and diluent for prolonged-release suspension for injection.

One (1) pre-filled syringe with the modified release powder for injection contains 75 mg of risperidone.

Risvan 100 mg powder and diluent for prolonged-release suspension for injection.

One (1) pre-filled syringe with the modified release powder for injection contains 100 mg risperidone.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Modified release, powder for injection.

Risvan is a modified release powder for injection of risperidone and appears as a white to white-yellowish non-aggregated powder contained within a pre-filled syringe.

Diluent for reconstitution.

The diluent appears as a clear solution free of visible particles contained within a pre-filled syringe.

4 Clinical Particulars

4.1 Therapeutic Indications

Risvan is indicated for the treatment of schizophrenia in adults for whom tolerability and effectiveness has been established with oral risperidone.

4.2 Dose and Method of Administration

Dosage.

Adults. Risvan should be administered every 28 days by intramuscular (IM) injection.
Risvan should be initiated according to the patient's clinical context:

Patients with history of previous response to risperidone who are currently stabilised with oral antipsychotics (mild to moderate psychotic symptoms).

Patients stabilised with oral risperidone can be switched to Risvan without previous titration. Patients stabilised on other oral antipsychotics (different from risperidone) should be titrated with oral risperidone before initiating treatment with Risvan. The duration of the titration period should be sufficiently long (at least 6 days) to confirm the tolerability and responsiveness to risperidone.

Patients never treated before with oral risperidone.

Patients who are candidates to receive Risvan and have not been previously treated with risperidone, the tolerability and responsiveness to risperidone must be confirmed with a period of oral risperidone treatment before initiating treatment with Risvan. The duration of the titration period is recommended to be at least 14 days.

Switching from oral risperidone to Risvan.

The recommended doses of oral risperidone and Risvan needed to maintain a similar active moiety steady-state exposure are as follows:
Previous oral risperidone dose of 3 mg/day to Risvan injection 75 mg every 28 days.
Previous oral risperidone dose of 4 mg/day or higher to Risvan injection 100 mg every 28 days.
Risvan must be initiated approximately 24 hours after the last oral risperidone dose. Dose adjustments of Risvan may be made every 28 days. A maintenance dose of Risvan 75 mg every 28 days is generally recommended. However, some patients may benefit from Risvan 100 mg every 28 days, according to the patient's clinical response and tolerability. Neither a loading dose nor any supplemental oral risperidone is recommended when using Risvan.

Switching from risperidone bi-weekly long-acting injection to Risvan.

When switching from risperidone bi-weekly long-acting injection, Risvan should be initiated in place of the next regularly scheduled injection of risperidone bi-weekly long-acting injection (i.e. two weeks after the last risperidone bi-weekly long-acting injection). Risvan should then be continued at 28-day intervals. No oral concomitant risperidone is recommended.
When switching patients previously stabilised on risperidone bi-weekly long-acting injection to Risvan, the recommended dose to maintain a similar active moiety steady-state exposure is as follows:
Risperidone bi-weekly long acting 37.5 mg to Risvan injection 75 mg every 28 days.
Risperidone bi-weekly long acting 50 mg to Risvan injection 100 mg every 28 days.

Switching from Risvan to oral risperidone.

When switching patients from Risvan injection back to oral risperidone therapy, the prolonged release characteristics of the formulation must be considered. In general, it is recommended to start oral risperidone treatment 28 days after the last Risvan administration.

Missed doses.

Avoiding missed doses.

To avoid a missed 28-day dose, patients may be given the injection up to 3 days before the 28-day time point. If a dose is delayed by 1 week, the median trough concentration decreases by approximately 50% during that week. The clinical relevance of this is unknown. If the dose is delayed, the next 28-day interval injection should be scheduled according to the last injection date.

Special populations.

Elderly.

Efficacy and safety of Risvan in elderly > 65 years have not been established for the Risvan prolonged-release suspension for injection. Risvan should be used with caution in elderly.
Tolerability to ≥ 3 mg daily oral risperidone should be reliably established prior to administration of Risvan.
In general, recommended dosing of risperidone for elderly patients with normal renal function is the same as for adult patients with normal renal function. However, if it is considered clinically appropriate, starting with 75 mg Risvan should be considered (see Renal impairment below for dosing recommendations in patients with renal impairment).

Renal impairment.

Risvan has not been systematically studied in patients with renal impairment.
For patients with mild renal impairment (creatinine clearance 60 to 89 mL/min) no dose adjustment is required for Risvan.
Risvan is not recommended in patients with moderate to severe renal impairment (creatinine clearance < 60 mL/min).

Hepatic impairment.

Risvan has not been systematically studied in patients with hepatic impairment. Patients with impaired hepatic function have increases in plasma concentration of the free fraction of risperidone.
Risvan should be used with caution in these groups of patients. A careful titration with oral risperidone (halving starting doses and slowing titration) before initiating treatment with Risvan at a dose of 75 mg is recommended if tolerability of an oral dose of at least 3 mg is confirmed.

Paediatric population.

The safety and efficacy of Risvan in children and adolescents less than 18 years have not been established. No data are available.
Use in one patient on one occasion only. Contains no antimicrobial preservative.
Risvan is only intended for intramuscular use and should not be administered intravenously or subcutaneously (see Section 4.4; Section 6.6) or by any other route. It should be administered by a healthcare professional.
Risvan should be administered by deep intramuscular deltoid or gluteal injection using the appropriate sterile needle. For deltoid administration, the 1-inch needle should be used alternating injections between the two deltoid muscles. For gluteal administration, the 2-inch needle should be used alternating injections between the two gluteal muscles.
The pre-filled syringe of Risvan powder should be reconstituted with the pre-filled syringe of accompanying diluent immediately prior to administration by injection.
The reconstitution process should be done accordingly to the Instructions for Use. An incorrect reconstitution could affect the correct dissolution of the powder and in case of administration a higher peak of risperidone could appear in the initial hours (overdose) and a lower AUC of the entire dose treatment (underdose).

Instructions for use Risvan 75 mg modified release powder for injection.

Important information. Risvan requires close attention to these step-by-step instructions for use to help ensure successful administration.
Use components provided: the components in the kit box are specifically designed for use with Risvan. Risvan must be reconstituted only with the diluent supplied in the kit box.
Do not substitute any components of the kit box.
Administer dose immediately after reconstitution. For intramuscular use only after reconstitution.
Proper dosing: The entire content of the reconstituted syringe must be administered to ensure intended dose of Risvan is delivered.

Single use device.

1. Check contents. Working on a clean surface, open the sachets and discard the desiccant pack.
The kit box of Risvan contains:
One aluminium foil pouch with a Risvan pre-filled syringe with a white plunger rod and white finger flange. The syringe is marked with 'R'.
One aluminium foil pouch with diluent for Risvan pre-filled syringe with a transparent plunger rod and a red finger flange. The syringe is marked with 'S'.
Two administration needles (21 G, 1 inch for deltoid [green cap] and a 20 G, 2 inch for gluteus [yellow cap]).
Discard the kit if any component is damaged. In the event of any foreign particulate matter and/or variation of physical aspect is observed, do not administer Risvan.

1.1 Inspect diluent syringe.

Ensure that diluent syringe content flows normally as a liquid. If it is frozen or partially frozen, warm it until it is completely thawed.

1.2 Dislodge powder syringe.

Tap the Risvan syringe to dislodge potential packed powder near the cap.
2. Connect the syringes.

2.1 Uncap syringes in upright position.

Hold both syringes in upright position to prevent loss of product.
Pull the cap off the diluent syringe.
Twist and pull the powder syringe cap off.

2.2 Connect the syringes.

Pick the diluent syringe 'S' that has the coloured finger flange and place it on top of the powder syringe 'R', or slightly lean it when connecting.
Twist the syringes together until you feel a slight resistance.
Make sure that powder syringe 'R' is in the upright position to prevent loss of product.
3. Mix the contents. Stop and read this section before starting or the medicine may not correctly reconstitute.
Push vigorously the diluent content towards the powder syringe.
Do not wait for powder wetting and quickly start mixing contents by pushing the plungers fast and alternately for 100 pushes (2 pushes within 1 second, approximately 1 minute).
Ensure medicine is passing between both syringes for a properly mixing: medicine is viscous and you will need to apply force when pressing on the plunger rods.
Mix for at least 100 pushes by doing alternately. Make sure medicine is passing between both syringes.
When medicine is correctly mixed, the appearance will be a uniform suspension off white to yellowish colour and thick consistency.
Once reconstituted, proceed immediately to prepare the injection syringe for administration to avoid loss of homogeneity.
4. Prepare injection syringe.

4.1 Transfer medicine.

Place downward pressure on the 'R' plunger rod and transfer all the content into the 'S' syringe that has attached the coloured finger flange.
Make sure all the content is transferred.

4.2 Detach syringes.

Once the medicine is fully transferred, separate the two syringes by untwisting.
Risvan should be administered immediately to avoid loss of homogeneity.

4.3 Attach the sterile needle with safety shield.

Choose the proper needle: Deltoid: 21 G, 1 inch for deltoid (green cap).
Gluteus: 20 G, 2 inches for gluteus (yellow cap).
Attach it using a clockwise twisting motion. Do not over-tighten.

4.4 Remove exceeding air.

Remove needle cover and push out the excess of air (only big bubbles) from the syringe barrel.
Do not expel any drops of medicine. If medicine is seen at the needle tip, pull back slightly on the plunger to prevent medicine spillage.
5. Administer and dispose.

5.1 Inject medicine.

Insert the needle fully into the muscle. Do not inject by any other route.
Thick medicine. Make sure to fully inject it.
The injection time is longer than usual due to the viscosity of the medicine.
Wait a few seconds before removing the needle.
Avoid inadvertent injection into a blood vessel.

5.2 Dispose medicine.

Cover the needle pressing on the needle guard using a finger or a flat surface and dispose immediately in a secure sharp's disposal container.
In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements (see Section 6.6).

Instructions for use Risvan 100 mg modified release powder for injection.

Important information. Risvan requires close attention to these step-by-step Instructions for use to help ensure successful administration.
Use components provided: the components in the kit box are specifically designed for use with Risvan. Risvan must be reconstituted only with the diluent supplied in the kit box.
Do not substitute any components of the kit box.
Administer dose immediately after reconstitution. For intramuscular use only after reconstitution.
Proper dosing: The entire content of the reconstituted syringe must be administered to ensure intended dose of Risvan is delivered.

Single use device.

1. Check contents. Working on a clean surface, open the sachets and discard the desiccant pack.
The kit box of Risvan contains:
One aluminium foil pouch with a Risvan pre-filled syringe with a white plunger rod and white finger flange. The syringe is marked with 'R'.
One aluminium foil pouch with diluent for Risvan pre-filled syringe with a transparent plunger rod and a blue finger flange. The syringe is marked with 'S'.
Two administration needles (21 G, 1 inch for deltoid [green cap] and a 20 G, 2 inch for gluteus [yellow cap]).
Discard the kit if any component is damaged. In the event of any foreign particulate matter and/or variation of physical aspect is observed, do not administer Risvan.

1.1 Inspect diluent syringe.

Ensure that diluent syringe content flows normally as a liquid. If it is frozen or partially frozen, warm it until it is completely thawed.

1.2 Dislodge powder syringe.

Tap the Risvan syringe to dislodge potential packed powder near the cap.
2. Connect the syringes.

2.1 Uncap syringes in upright position.

Hold both syringes in upright position to prevent loss of product.
Pull the cap off the diluent syringe.
Twist and pull the powder syringe cap off.

2.2 Connect the syringes.

4.1 Transfer medicine.

Place downward pressure on the 'R' plunger rod and transfer all the content into the 'S' syringe that has attached the coloured finger flange.
Make sure all the content is transferred.

4.2 Detach syringes.

Once the medicine is fully transferred, separate the two syringes by untwisting. Risvan should be administered immediately to avoid loss of homogeneity.

4.3 Attach the safety needle with safety shield.

Choose the proper needle: Deltoid: 21 G, 1 inch for deltoid (green cap).
Gluteus: 20 G, 2 inches for gluteus (yellow cap).
Attach it using a clockwise twisting motion. Do not over-tighten.

4.4 Remove exceeding air.

5.1 Inject medicine.

5.2 Dispose medicine.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1 List of Excipients.

4.4 Special Warnings and Precautions for Use

For risperidone-naive patients, it is recommended to establish tolerability with oral risperidone prior to initiating treatment with Risvan (see Section 4.2 Dose and Method of Administration). Consideration should be given to the prolonged release nature of the medicinal product and the long elimination half-life of risperidone when assessing treatment needs and the potential need to be able to discontinue treatment.

Use in the elderly patients with dementia.

Increased mortality in elderly people with dementia.

Risvan has not been studied in elderly patients with dementia, hence it is not indicated for use in this group of patients. In a meta-analysis of 17 controlled trials of atypical antipsychotics, including risperidone, elderly patients with dementia treated with atypical antipsychotics have an increased mortality compared to placebo. In placebo-controlled trials with oral risperidone in this population, the incidence of mortality was 4% for risperidone-treated patients compared to 3.1% for placebo-treated patients. The odds ratio (95% exact confidence interval) was 1.21 (0.7; 2.1). The mean age (range) of patients who died was 86 years (range 67-100). Data from two large observational studies showed that elderly people with dementia who are treated with conventional antipsychotics are also at a small increased risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic active substance as opposed to some characteristic(s) of the patients is not clear.

Concomitant use with furosemide.

In the risperidone placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75-97) when compared to patients treated with risperidone alone (3.1%; mean age 84 years, range 70-96) or furosemide alone (4.1%; mean age 80 years, range 67-90). The increase in mortality in patients treated with furosemide plus risperidone was observed in two of the four clinical trials. Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low dose) was not associated with similar findings.
No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and benefits of this combination or co-treatment with other potent diuretics should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be carefully avoided in elderly patients with dementia.

Cerebrovascular adverse reactions.

An approximately 3-fold increased risk of cerebrovascular adverse events (CVAEs) have been seen in randomised placebo-controlled clinical trials in the dementia population with some atypical antipsychotics. The pooled data from six placebo-controlled studies with risperidone in mainly elderly patients (> 65 years of age) with dementia showed that CVAEs (serious and non-serious, combined) occurred in 3.3% (33/1,009) of patients treated with risperidone and 1.2% (8/712) of patients treated with placebo. The odds ratio (95% exact confidence interval) was 2.96 (1.34; 7.50). The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations.
Risvan should be used with caution in patients with risk factors for stroke.

Orthostatic hypotension.

Due to the alpha-blocking activity of risperidone, (orthostatic) hypotension can occur. Some cases of hypotension or orthostatic hypotension have been reported during the clinical development program of Risvan at doses ranged from 50 mg to 100 mg. Clinically significant hypotension has been observed post-marketing with concomitant use of risperidone and antihypertensive treatment. Risvan should be used with caution in patients with known cardiovascular disease (e.g. heart failure, myocardial infarction, conduction abnormalities, dehydration, hypovolaemia, or cerebrovascular disease). The risk/benefit of further treatment with Risvan should be assessed if clinically relevant orthostatic hypotension persists.

Leukopenia, neutropenia, and agranulocytosis.

Events of leukopenia, neutropenia and agranulocytosis have been reported with risperidone. Agranulocytosis has been reported very rarely (< 1/10,000 patients) during post-marketing surveillance.
Patients with a history of a clinically significant low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia should be monitored during the first few months of therapy and discontinuation of Risvan should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count < 1 x 10⁹/L) should discontinue Risvan and have their WBC followed until recovery.

Tardive dyskinesia/extrapyramidal symptoms (TD/EPS).

Medicines with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia (TD) characterised by rhythmical involuntary movements, predominantly of the tongue and/or face. The onset of extrapyramidal symptoms (EPS) is a risk factor for TD. If signs and symptoms of TD appear, the discontinuation of all antipsychotics should be considered.
Caution is warranted in patients receiving both psychostimulants (e.g. methylphenidate) and risperidone concomitantly, as EPSs could emerge when adjusting one or both medicines. Gradual withdrawal of stimulant treatment is recommended (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Neuroleptic malignant syndrome (NMS).

Neuroleptic Malignant Syndrome (NMS) characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels has been reported to occur with antipsychotics. Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. In this event, Risvan should be discontinued.

Parkinson's disease and dementia with Lewy bodies.

Physicians should weigh the risks versus the benefits when prescribing Risvan to patients with Parkinson's disease or Dementia with Lewy Bodies (DLB). Parkinson's disease may worsen with risperidone. Both groups may be at increased risk of Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotic medicinal products; these patients were excluded from clinical trials. Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms.

Hyperglycaemia and diabetes mellitus.

Hyperglycaemia, diabetes mellitus, and exacerbation of pre-existing diabetes have been reported during treatment with risperidone. In some cases, a prior increase in body weight has been reported which may be a predisposing factor. Association with ketoacidosis has been reported very rarely and rarely with diabetic coma. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines. Patients treated with Risvan should be monitored for symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and weakness) and patients with diabetes mellitus should be monitored regularly for worsening of glucose control.

Weight gain.

Significant weight gain has been reported with risperidone use. Weight should be monitored regularly.

Hyperprolactinaemia.

Hyperprolactinaemia is a common side effect of treatment with risperidone. Evaluation of the prolactin plasma level is recommended in patients with evidence of possible prolactin-related side effects (e.g. gynaecomastia, menstrual disorders, anovulation, fertility disorder, decreased libido, erectile dysfunction, and galactorrhoea).
Tissue culture studies suggest that cell growth in human breast tumours may be stimulated by prolactin. Although no clear association with the administration of antipsychotics has so far been demonstrated in clinical and epidemiological studies, caution is recommended in patients with relevant medical history. Risvan should be used with caution in patients with pre-existing hyperprolactinaemia and in patients with possible prolactin-dependent tumours.

QT prolongation.

QT prolongation has very rarely been reported. Caution should be exercised when risperidone is prescribed in patients with known cardiovascular disease, family history of QT prolongation, bradycardia, or electrolyte disturbances (hypokalaemia, hypomagnesaemia), as it may increase the risk of arrhythmogenic effects, and in concomitant use with medicines known to prolong the QT interval.

Seizures.

Risvan should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Priapism.

Priapism may occur with Risvan treatment due to its alpha-adrenergic blocking effects.

Body temperature regulation.

Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic medicines. Appropriate care is advised when prescribing Risvan to patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g. exercising strenuously, exposure to extreme heat, receiving concomitant treatment with anticholinergic activity, or being subject to dehydration.

Antiemetic effect.

An antiemetic effect was observed in preclinical studies with risperidone. This effect, if it occurs in humans, may mask the signs and symptoms of overdosage with certain medicines or of conditions such as intestinal obstruction, Reye's syndrome, and brain tumour.

Venous thromboembolism.

Cases of venous thromboembolism (VTE) have been reported with antipsychotic medicinal products. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Risvan and preventative measures undertaken.

Intraoperative floppy iris syndrome.

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in patients treated with medicines with risperidone (see Section 4.8 Adverse Effects (Undesirable Effects)).
IFIS may increase the risk of eye complications during and after the operation. Current or past use of medicines with alpha_1a-adrenergic antagonist effect should be made known to the ophthalmic surgeon in advance of surgery. The potential benefit of stopping alpha₁-blocking therapy prior to cataract surgery has not been established and must be weighed against the risk of stopping the antipsychotic therapy.

Hypersensitivity.

Although tolerability of oral risperidone should be established prior to initiating treatment in patients who have not been previously treated with risperidone, rarely anaphylactic reactions have been reported during post-marketing experience with parenteral risperidone in patients who have previously tolerated oral risperidone. If hypersensitivity reactions occur, the use of Risvan should be discontinued, and general supportive measures should be initiated as clinically appropriate, and the patient should be monitored until signs and symptoms resolve.

Reconstitution and administration.

A lack of efficacy can occur in case of incorrect reconstitution (see Section 4.2 Dose and Method of Administration; Section 6.6 Special Precautions for Disposal).
Care must be taken to avoid inadvertent injection of Risvan into a blood vessel or subcutaneous tissue. If administered intravenously, it is expected that a solid formation will be formed immediately due to the characteristics of Risvan, producing a blockage of the needle. Consequently, a bleeding could occur at the injection site. In case the administration is subcutaneous, the injection might be more painful, and a slower release of risperidone is expected.
If a dose is incorrectly administered by intravenous or subcutaneous route, the dose should not be repeated since it is difficult to estimate the exposure to the medicine. The patient should be closely monitored and managed as clinically appropriate until the next scheduled 28-day interval injection of Risvan.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The interactions of Risvan with co-administration of other medicinal products have not been systematically evaluated. The interaction data provided in this section are based on studies with oral risperidone.

Pharmacodynamic-related interactions.

Medicinal products known to prolong the QT interval.

Caution is advised when prescribing Risvan with medicinal products known to prolong the QT interval, such as antiarrhythmics (e.g. quinidine, disopyramide, procainamide, propafenone, amiodarone, sotalol), tricyclic antidepressants (i.e. amitriptyline), tetracyclic antidepressants (i.e. maprotiline), some antihistamines, other antipsychotics, some antimalarials (i.e. quinine and mefloquine), and with medicines causing electrolyte imbalance (hypokalaemia, hypomagnesaemia), bradycardia, or those which inhibit the hepatic metabolism of risperidone. This list is indicative and not exhaustive.

Centrally acting medicinal products and alcohol.

Risvan should be used with caution in combination with other centrally acting substances, notably including alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.

Levodopa and dopamine agonists.

Risvan may antagonise the effect of levodopa and other dopamine agonists. If this combination is deemed necessary, particularly in end-stage Parkinson's disease, the lowest effective dose of each treatment should be prescribed.

Medicinal products with hypotensive effect.

Clinically significant hypotension has been observed post-marketing with concomitant use of risperidone and antihypertensive treatment.

Psychostimulants.

The combined use of psychostimulants (e.g. methylphenidate) with Risvan can lead to extrapyramidal symptoms upon change of either or both treatments (see Section 4.4 Special Warnings and Precautions for Use).

Paliperidone.

Concomitant use of Risvan with paliperidone is not recommended as paliperidone is the active metabolite of risperidone and the combination of the two may lead to additive active moiety exposure.

Pharmacokinetic-related interactions.

Risvan is mainly metabolised through Cytochrome P (CYP)2D6, and to a lesser extent through CYP3A4. Both risperidone and its active metabolite 9-hydroxy-risperidone are substrates of P-glycoprotein (P-gp). Substances that modify CYP2D6 activity, or substances strongly inhibiting or inducing CYP3A4 and/or P-gp activity, may influence the pharmacokinetics of the risperidone active moiety.

Strong CYP2D6 inhibitors.

Co-administration of Risvan with a strong CYP2D6 inhibitor may increase the plasma concentrations of risperidone, but less so of the active moiety. Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone active moiety (e.g. paroxetine, see below). It is expected that other CYP2D6 inhibitors, such as quinidine, may affect the plasma concentrations of risperidone in a similar way. When concomitant paroxetine, quinidine, or another strong CYP2D6 inhibitor, especially at higher doses, is initiated or discontinued, the physician should re-evaluate the dosing of Risvan.

CYP3A4 and/or P-gp inhibitors.

Co-administration of Risvan with a strong CYP3A4 and/or P-gp inhibitor may substantially elevate plasma concentrations of the risperidone active moiety. When concomitant itraconazole or another strong CYP3A4 and/or P-gp inhibitor is initiated or discontinued, the physician should re-evaluate the dosing of Risvan.

CYP3A4 and/or P-gp inducers.

Co-administration of Risvan with a strong CYP3A4 and/or P-gp inducer may decrease the plasma concentrations of the risperidone active moiety. When concomitant carbamazepine or another strong CYP3A4 and/or P-gp inducer is initiated or discontinued, the physician should re-evaluate the dosing of Risvan. CYP3A4 inducers exert their effect in a time-dependent manner and may take at least 2 weeks to reach maximal effect after introduction. Conversely, on discontinuation, CYP3A4 induction may take at least 2 weeks to decline.

Highly protein-bound medicinal products.

When risperidone is taken together with highly protein-bound medicinal products, there is no clinically relevant displacement of either medicine from the plasma proteins. When using concomitant medicinal products, the corresponding label should be consulted for information on the route of metabolism and the possible need to adjust dosage.

Examples.

Examples of medicinal products that may potentially interact or that were shown not to interact with risperidone are listed below:
Effect of other medicinal products on the pharmacokinetics of risperidone.

Antibacterials.

Erythromycin, a moderate CYP3A4 inhibitor and P-gp inhibitor, does not change the pharmacokinetics of risperidone and the active moiety.
Rifampicin, a strong CYP3A4 inducer and a P-gp inducer, decreased the plasma concentrations of the active moiety.

Anticholinesterases.

Donepezil and galantamine, both CYP2D6 and CYP3A4 substrates, do not show a clinically relevant effect on the pharmacokinetics of risperidone and the active moiety.

Antiepileptics.

Carbamazepine, a strong CYP3A4 inducer and a P-gp inducer, has been shown to decrease the plasma concentrations of the active moiety. Similar effects may be observed with e.g. phenytoin and phenobarbital which also induce CYP3A4 hepatic enzyme, as well as P-glycoprotein.
Topiramate modestly reduced the bioavailability of risperidone, but not that of the active moiety. Therefore, this interaction is unlikely to be of clinical significance.

Antifungals.

Itraconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of the active moiety by about 70%, at risperidone doses of 2 to 8 mg/day.
Ketoconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of risperidone and decreased the plasma concentrations of 9-hydroxy-risperidone.

Antipsychotics.

Phenothiazines may increase the plasma concentrations of risperidone but not those of the active moiety.

Antivirals.

Protease inhibitors: No formal study data are available; however, since ritonavir is a strong CYP3A4 inhibitor and a weak CYP2D6 inhibitor, ritonavir and ritonavir-boosted protease inhibitors potentially raise concentrations of the risperidone active moiety.

Beta-blockers.

Some beta-blockers may increase the plasma concentrations of risperidone but not those of the active moiety.

Calcium channel blockers.

Verapamil, a moderate inhibitor of CYP3A4 and an inhibitor of P-gp, increases the plasma concentration of risperidone and the active moiety.

Gastrointestinal drugs.

H₂-receptor antagonists: Cimetidine and ranitidine, both weak inhibitors of CYP2D6 and CYP3A4, increased the bioavailability of risperidone, but only marginally that of the active moiety.

Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants.

Fluoxetine, a strong CYP2D6 inhibitor, increases the plasma concentration of risperidone, but less so of the active moiety.
Paroxetine, a strong CYP2D6 inhibitor, increases the plasma concentrations of risperidone, but, at dosages up to 20 mg/day, less so of the active moiety. However, higher doses of paroxetine may elevate concentrations of the risperidone active moiety.
Sertraline, a weak inhibitor of CYP2D6, and fluvoxamine, a weak inhibitor of CYP3A4, at dosages up to 100 mg/day are not associated with clinically significant changes in concentrations of the risperidone active moiety. However, doses higher than 100 mg/day of sertraline or fluvoxamine may elevate concentrations of the risperidone active moiety.
Tricyclic antidepressants may increase the plasma concentrations of risperidone but not those of the active moiety. Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction.
Effect of risperidone on the pharmacokinetics of other medicinal products.

Antiepileptics.

Risperidone does not show a clinically relevant effect on the pharmacokinetics of valproate or topiramate.

Antipsychotics.

Aripiprazole, a CYP2D6 and CYP3A4 substrate. Risperidone tablets or injections did not affect the pharmacokinetics of the sum of aripiprazole and its active metabolite, dehydroaripiprazole.

Digitalis glycosides.

Risperidone does not show a clinically relevant effect on the pharmacokinetics of digoxin.

Lithium.

Risperidone does not show a clinically relevant effect on the pharmacokinetics of lithium.

Concomitant use of risperidone with furosemide.

See Section 4.4 Special Warnings and Precautions for Use regarding increased mortality in elderly patients with dementia concomitantly receiving furosemide.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Risperidone impaired mating, but not fertility, in Wistar rats at doses 0.2 to 5 times the maximum human dose on a mg/m² basis. The effect appeared to be in females since the oestrus cycle in rats was disrupted by risperidone and impaired mating behaviour was not noted when males only were treated. In repeat dose toxicity studies in Beagle dogs, risperidone at dose of 1 to 17 times the maximum human dose on a mg/m² basis was associated with adverse effects on the male reproductive system (inhibited ejaculation, incomplete spermatogenesis, reduced sperm motility and concentration, reduced gonadal and prostatic weight, prostatic immaturity, decreased serum testosterone). Serum testosterone and sperm parameters partially recovered but remained decreased after treatment was discontinued. No-effect doses were not determined in either rat or dog.
(Category C)
Risperidone has only been taken by a limited number of pregnant women or women of childbearing age. No increases in the frequency of malformation or other direct or indirect harmful effects on the human fetus have been observed.
A retrospective observational cohort study based on a US claims database compared the risk of congenital malformations for live births among women with and without antipsychotic use during the first trimester of pregnancy. The risk of congenital malformations with risperidone, after adjusting for confounder variables available in the database, was elevated compared to no antipsychotic exposure (relative risk=1.26, 95% CI: 1.02-1.56). No biological mechanism has been identified to explain these findings and teratogenic effects have not been observed in non-clinical studies.
In an embryo foetal development study in rats, intramuscular administration of risperidone delayed ossification in the metatarsals and mandible at risperidone plus 9-hydroxy risperidone levels less than those achieved at the maximal human dose. This is unlikely to be clinically relevant. There was no effect on the incidence of malformations.

Non-teratogenic class effect.

Neonates exposed to antipsychotic drugs (including risperidone) during the third trimester of pregnancy are at risk of experiencing extrapyramidal neurological disturbances and/or withdrawal symptoms following delivery. There have been post-market reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeling disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited; in other cases neonates have required additional medical treatment or monitoring. Risvan should be used during pregnancy only if the anticipated benefit outweighs the risk and the administered dose and duration of treatment should be as low and as short as possible.
It has been demonstrated that risperidone and 9-hydroxyrisperidone are excreted in human breast milk. It is recommended that women receiving risperidone should not breast feed. Risperidone and 9-hydroxyrisperidone are excreted in milk in lactating dogs. In rats, administration of risperidone during late gestation and lactation was associated with an increase in pup deaths during the first 4 days of lactation at doses 0.2 to 5 times the maximum human dose on a mg/m² basis. A no-effect dose was not determined. It is not known whether these deaths were due to a direct effect on the foetuses or pups or to effects on the dams. In one such study there was an increase in stillborn rat pups at a dose 2.5 times the maximum human dose on a mg/m² basis.

4.7 Effects on Ability to Drive and Use Machines

Risvan can have minor or moderate influence on the ability to drive and use machines due to potential nervous system and visual effects (see Section 4.8 Adverse Effects (Undesirable Effects)). Therefore, patients should be advised not to drive or operate machinery until their individual susceptibility is known.

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

The most frequently reported adverse drug reactions (ADRs) that were reported in a phase 3 clinical trial are: blood prolactin increased (11.7%), hyperprolactinaemia (7.2%), akathisia (5.5%), headache (4.8%), somnolence (4.1%), weight increased (3.8%), injection site pain (3.1%) and dizziness (3.1%).

Tabulated list of adverse events.

Table 1 are treatment-emergent adverse events occurring in ≥ 2% of risperidone ISM patients by system organ class and preferred term - DB phase (SAF population) of clinical study report of Prisma 3 clinical trial.

Tabulated list of adverse reactions.

Table 2 are all the ADRs that were reported in clinical trials and post-marketing experience with risperidone by frequency category estimated from risperidone clinical trials. The following terms and frequencies are applied: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Description of selected adverse reactions.

Injection site reactions.

The most commonly reported injection site related adverse reaction was pain. In the phase 3 study 14 out of 386 patients (3.6%) reported 18 cases of injection pain reactions after 2,827 injections (0.6%) of Risvan. The majority of these reactions were reported to be of mild to moderate severity. Subject evaluations of injection site pain based on a visual analogue scale tended to lessen in frequency and intensity over time.

Cardiac disorders.

Postural orthostatic tachycardia syndrome.

Class effects.

Very rare cases of QT prolongation ventricular arrhythmias (ventricular fibrillation, ventricular tachycardia), sudden death, cardiac arrest and Torsades de Pointes have been reported post marketing with risperidone.

Venous thromboembolism.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis, have been reported with antipsychotic drugs (frequency unknown).

Changes in body weight.

Data from a 12-week double-blind (DB), placebo-controlled trial indicated that there was a mean increase in weight from baseline of 1.4 (-8 to 18) kg, 0.8 (-8 to 47) kg, and 0.2 (-12 to 18) kg after treatment with the Risvan 75 mg, Risvan 100 mg and placebo, respectively.

Paediatric population.

No information exists on efficacy and safety of Risvan in children.

Elder patients.

Limited information exists on efficacy and safety of Risvan in older patients with schizophrenia or dementia. In clinical trials with oral risperidone transient ischaemic attack and cerebrovascular accident were reported with a frequency of 1.4% and 1.5%, respectively, in older patients with dementia compared to other adults. In addition, the following ADRs were reported with a frequency ≥ 5% in older patients with dementia and with at least twice the frequency seen in other adult populations: urinary tract infection, peripheral oedema, lethargy, and cough.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

In general, reported signs and symptoms have been those resulting from an exaggeration of the known pharmacological effects of risperidone. These include drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. In overdose, QT prolongation and convulsions have been reported. Torsade de Pointes has been reported in association with combined overdose of risperidone and paroxetine.
In case of acute overdose, the possibility of multiple drug involvement should be considered.

Treatment.

A clear airway should be established and maintained, and adequate oxygenation and ventilation should be ensured. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias.
There is no specific antidote to Risvan. Therefore, appropriate supportive measures should be instituted. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. In case of severe extrapyramidal symptoms, an anticholinergic medicinal product should be administered. Close medical supervision and monitoring should continue until the patient recovers.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Risperidone is a selective monoaminergic antagonist with a high affinity for serotoninergic 5-HT₂ and dopaminergic D2 receptors. Risperidone binds also to alpha₁-adrenergic receptors, and with lower affinity, to H1-histaminergic and alpha₂-adrenergic receptors. Risperidone has no affinity for cholinergic receptors. The antipsychotic activity of risperidone is considered to be attributable to both risperidone and its active metabolite 9-hydroxy risperidone.
Central dopamine D2 receptor antagonism is considered to be the mechanism of action by which conventional neuroleptics improve the positive symptoms of schizophrenia, but also induce extrapyramidal symptoms and release of prolactin.
Although risperidone antagonises dopamine D2 receptors and causes release of prolactin, it is less potent than classical neuroleptics for depression of motor activity and for induction of catalepsy in animals.
Balanced central serotonin and dopamine antagonism may reduce extrapyramidal side effect liability and extend the therapeutic activity to the negative and affective symptoms of schizophrenia.
Due to the alpha-blocking activity of risperidone, orthostatic hypotension can occur, especially during the initial dose-titration period. This alpha-blocking activity may also induce nasal mucosal swelling, which is probably related to the observed incidence of rhinitis associated with the use of risperidone.
Antagonism of serotoninergic and histaminergic receptors may induce body weight gain. In controlled clinical trials, risperidone was found to improve positive symptoms (such as hallucinations, delusions, thought disturbances, hostility, suspiciousness), as well as negative symptoms (such as blunted affect, emotional and social withdrawal, poverty of speech). Risperidone may also alleviate affective symptoms (such as depression, guilt feelings, anxiety) associated with schizophrenia.

Clinical trials.

A therapeutic plasma concentration range of 7.5 nanogram/mL to 80 nanogram/mL was used for dose selection rationale during the clinical development plan of Risvan. This range is based on the expected pharmacodynamic translation of an optimal striatal D2 receptor occupancy (D2RO) of 50%-80%, as suggested by the scientific evidence. The recommended dosage of Risvan, i.e. 75 mg and 100 mg every 28 days, provides a similar exposure to what it is observed after daily oral administration of risperidone 3 mg and 4 mg, respectively.
The efficacy of Risvan (75 mg and 100 mg) in the treatment of schizophrenia in adults was established in one Phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel groups study. The study admitted patients with an acute exacerbation or relapse of schizophrenia (DSM-5 criteria), who had a Positive and Negative Syndrome Scale (PANSS) score of 80-120. At the screening visit, all risperidone naïve patients received 2 mg/day oral risperidone for 3 days to ensure a lack of any clinically significant hypersensitivity reactions before the trial. Patients with previous history of being treated with risperidone did not receive oral risperidone at the screening and started directly with Risvan (75 mg or 100 mg) or placebo after randomization. Four hundred and thirty-eight (438) patients were randomised to receive 3 intramuscular doses of Risvan (75 mg or 100 mg) or placebo every 28 days. The mean age of patients was 42.0 (SD: 11.02) years.
No patients < 18 years or > 65 years were included. Demographic and other baseline characteristics were similar in each treatment group. No supplemental oral risperidone was permitted during the study.
The primary endpoint was the change in PANSS total score from baseline to end of study (Day 85). Both Risvan 75 and 100 mg doses demonstrated a statistically significant improvement compared with placebo based on the primary endpoint (Table 3 and Figure 1). These results support efficacy across the entire duration of treatment and improvement in PANSS and was observed as early as day 4 with significant separation from placebo in the 100 mg and 75 mg groups by day 8 and 15, respectively. Similar to the PANSS total score, the three PANSS positive, negative and general psychopathological subscale scores also showed an improvement (decrease) from baseline over time.

The key secondary efficacy endpoint was defined as the mean change from baseline at day 85 on the Clinical Global Impression - Severity (CGI-S) score. Both Risvan treatment groups demonstrated statistically significantly better CGI-S scores versus placebo from day 8 onwards (-0.4 (0.05) and -0.6 (0.05) score reduction from baseline for 75 mg and 100 mg, respectively).
Overall response (PANSS total score reduction > 30% and/or CGI-I of 2 "much improved" or 1 "very much improved") rate at endpoint for Risvan was 56% and showed to be statistically significant from day 8 and 15 onwards, for both doses in comparison to placebo.
The long-term (12 months) efficacy of Risvan was evaluated in an open-label extension of the main study in 215 patients with schizophrenia. The extension study was open to enrolment for patients from the DB phase (rollover patients) and stable patients not previously enrolled in the study (de novo patients). The de novo patients were switched from oral risperidone directly to Risvan 75 mg or 100 mg. Efficacy was maintained over time with a relapse rate 10.7% (95% CI, 6.9% to 15.6%) and a remittance rate 61.0% (95% CI, 53.7% to 68.4%).

5.2 Pharmacokinetic Properties

Risperidone is metabolised to 9-hydroxy-risperidone, which has a similar pharmacological activity to risperidone (see Metabolism and Excretion).

Absorption.

Risvan contains risperidone in a suspension delivery system that shows a combined absorption process. Following intramuscular injection, a small amount of the drug is immediately released at the moment of the injection that provides immediate plasma levels. After a first peak concentration, mean plasma concentrations decrease sustainedly through Day 14 and then increased again to reach a second peak between approximately Day 21 and Day 24. Following the second peak, plasma concentrations decreased gradually over time. The suspension forms a depot that provides sustained therapeutic plasma concentrations that are maintained over the 28-day interval.
After single IM injection of Risvan 75 and 100 mg, mean active moiety concentrations of 13 ± 9 and 29 ± 13 nanogram/mL respectively are achieved at 2 hours after administration. Active moiety plasma concentrations of 17 ± 8 and 21 ± 17 nanogram/mL respectively one month after administration, and in most of the patients the drug is completely eliminated 75 days after administration, with active moiety values lower than 1 nanogram/mL.
The mean trough plasma concentrations (C_trough) and mean maximum peak plasma concentrations (C_max) of active moiety following repeated intramuscular injections with Risvan are shown in Table 4.

Distribution.

Risperidone is rapidly distributed. The volume of distribution is 1-2 L/kg. In plasma, risperidone is bound to albumin and alpha₁-acid glycoprotein. The plasma protein binding of risperidone is 90%, that of 9-hydroxy-risperidone is 77%.

Metabolism.

Risperidone is metabolised by CYP2D6 to 9-hydroxy-risperidone, which has a similar pharmacological activity as risperidone. Risperidone plus 9-hydroxy-risperidone form the active moiety. CYP2D6 is subject to genetic polymorphism. Extensive CYP2D6 metabolisers convert risperidone rapidly into 9-hydroxy-risperidone, whereas poor CYP2D6 metabolisers convert it much more slowly. Although extensive metabolisers have lower risperidone and higher 9-hydroxy-risperidone concentrations than poor metabolisers, the pharmacokinetics of risperidone and 9-hydroxy-risperidone combined (i.e. the active moiety), after single and multiple doses, are similar in extensive and poor metabolisers of CYP2D6.
Another metabolic pathway of risperidone is N-dealkylation. In vitro studies in human liver microsomes showed that risperidone at clinically relevant concentration does not substantially inhibit the metabolism of medicines metabolised by cytochrome P450 isozymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5.

Excretion.

One week after administration, 70% of the dose is excreted in the urine and 14% in the faeces. In urine, risperidone plus 9-hydroxy-risperidone represents 35-45% of the dose. The remainder is inactive metabolites. After oral administration to psychotic patients, risperidone is eliminated with a half-life of about 3 hours. The elimination half-life of 9-hydroxy-risperidone and of the active moiety is 24 hours.
The active moiety is eliminated within 75 days after Risvan administration, with active moiety values lower than 1 nanogram/mL in most of the patients.

Risvan injection versus oral risperidone.

Initial plasma levels with Risvan were within the exposure range observed with 3-4 mg of oral risperidone. Steady state exposure after Risvan 100 mg compared to 4 mg oral risperidone was 39% higher for AUC and 32% for C_max and was similar for C_min. Simulations based on population pharmacokinetic modelling shows that Risvan 75 mg exposure is similar to 3 mg oral risperidone in steady state.
When switching from oral risperidone to Risvan, the predicted exposure to the active moiety is in a similar range, including peak concentrations.

Linearity/non-linearity.

Risvan has been found to exhibit linear and dose-proportional pharmacokinetics at doses of 75 and 100 mg.

Elderly.

Risvan has not been systematically studied in elderly patients (see Section 4.2 Dose and Method of Administration).

Renal impairment.

Risvan has not been systematically studied in patients with renal impairment. Patients with mild renal impairment (creatinine clearance 60 to 89 mL/min) that received Risvan administration, showed similar active moiety exposure than patients with normal renal function. No data is available in moderate renal disease or severe renal disease.

Hepatic impairment.

Risvan has not been systematically studied in patients with hepatic impairment.

Body mass index (BMI).

Population pharmacokinetic simulations have shown potential increases in plasma concentrations of Risvan in obese or morbid obese females in comparison with normal weight patients with insignificant clinical impact.

Gender, race and smoking habits.

A pop PK analysis revealed no apparent effect of gender, race or smoking habits on the pharmacokinetics of risperidone or the active moiety.

5.3 Preclinical Safety Data

Genotoxicity.

No evidence of risperidone genotoxicity was observed in assays for DNA damage, gene mutations or chromosomal damage. Risvan was not genotoxic in a bacterial reverse mutation assay.

Carcinogenicity.

Risperidone was administered in the diet to Swiss albino mice for 18 months and to Wistar rats for 25 months at doses equivalent to 0.3, 1.3 and 5 times the maximum human dose of 10 mg/day (mice) or 0.6, 2.5 and 10 times the maximum human dose (rats) on a mg/m² basis. There were statistically significant increases in pituitary gland adenomas in female mice and endocrine pancreas adenomas in male rats at the two highest dose levels, and in mammary gland adenocarcinomas at all dose levels in female mice and female rats and at the highest dose in male rats.
Antipsychotic medicines have been shown to chronically elevate prolactin levels in rodents. Serum prolactin levels were not measured during the risperidone carcinogenicity studies; however, measurements during subchronic toxicity studies showed that risperidone elevated serum prolactin levels 5 to 6-fold in mice and rats at the same doses used in the carcinogenicity studies. An increase in mammary, pituitary and endocrine pancreas neoplasms has been found in rodents after chronic administration of other dopamine receptor antagonists and is considered to be prolactin mediated.
In a 2-year IM carcinogenicity study in rats, increased incidences of mammary gland adenocarcinoma, pancreatic islet-cell adenoma, adrenal gland phaeochromocytoma, pituitary gland adenoma and renal corticotubular adenoma were observed with systemic exposure (plasma AUC) to risperidone plus 9-hydroxy risperidone about twice that anticipated in humans at the maximal recommended clinical dose of Risvan. Increased incidences of mammary adenocarcinoma were also observed at doses for which the plasma AUC of risperidone plus 9-hydroxy risperidone was less than anticipated clinical exposure, a no-effect dose for this finding was not determined. Elevated plasma concentrations of prolactin were present after one year of treatment, but the relationship between the renal tubular tumours and prolactin is uncertain. The increase in phaeochromocytomas was associated with hypercalcemia but there was no evidence for a causal relationship. However, phaeochromocytomas associated with hypercalcemia is a common finding in rats and is likely to be of low relevance to humans.
The relevance for human risk of the findings of prolactin-mediated endocrine tumours in rodents is unknown. In controlled clinical trials, risperidone elevated serum prolactin levels more than haloperidol, although to date neither clinical studies nor epidemiological studies have shown an association between chronic administration of these medicines and mammary tumorigenesis. However, since tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, risperidone should be used cautiously in patients with previously detected breast cancer or in patients with pituitary tumours. Possible manifestations associated with elevated prolactin levels are amenorrhoea, galactorrhoea and menorrhagia (see Section 4.8 Adverse Effects (Undesirable Effects)).
Local irritation at the injection site was observed in dogs and rats after administration of risperidone. In a 2-year IM carcinogenicity study in rats, no increased incidence of injection site tumours was seen in either the vehicle or active drug groups.

6 Pharmaceutical Particulars

6.1 List of Excipients

Pre-filled syringe of powder.

polyglactin.

Pre-filled syringe of diluent.

dimethyl sulfoxide.

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in Section 6.6 Special Precautions for Disposal.

6.3 Shelf Life

Risvan should be used immediately after reconstitution.
In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.
Store in the original package in order to protect from moisture.
For storage conditions after reconstitution of the medicinal product, see Section 6.3 Shelf Life.

6.5 Nature and Contents of Container

Powder prefilled syringe.

Cyclic olefin polymer syringe with a nozzle cap and plunger stopper composed of chlorobutyl rubber covered with a polytetrafluoroethylene.

Diluent prefilled syringe.

Cyclic olefin polymer syringe with a tip cap composed of chlorobutyl rubber, and a plunger stopper composed of bromobutyl rubber covered with ethylene-tetrafluoroethylene copolymer. The diluent for reconstitution is presented in the following dosage strengths:
Pre-filled syringe of diluent containing 0.383 mL of dimethyl sulfoxide (diluent for Risvan 75 mg).
Pre-filled syringe of diluent containing 0.490 mL of dimethyl sulfoxide (diluent for Risvan 100 mg).
Each kit box of Risvan contains:
An aluminium foil pouch with one pre-filled syringe containing powder and a silica gel desiccant sachet.
An aluminium foil pouch with one pre-filled syringe containing the diluent and a silica gel desiccant sachet.
One needle for injection 2 inch (0.90 x 51 mm [20 G]) with safety shield used for gluteus administration.
One needle for injection 1 inch (0.80 x 25 mm [21 G]) with safety shield used for deltoid administration.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Risperidone is a white to off white crystalline powder, practically insoluble in water, freely soluble in methylene chloride, sparingly soluble in ethanol (96%) and soluble in dilute acid solutions.

Chemical structure.

Risperidone is chemically identified as 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl] ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
Structural formula:

Molecular formula of risperidone is C₂₃H₂₇FN₄O₂ and molecular mass is 410.48 g/mol.

CAS number.

106266-06-2.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

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