FINAL AMENDED PACKAGE INSERT

MCC approved 28 November 2014

CCDS Jan 2013 of 56

PACKAGE INSERT

SCHEDULING STATUS

Schedule 5.

PROPRIETARY NAME AND DOSAGE FORM

RISPERDAL® CONSTA® 25 mg prolonged release suspension for intramuscular injection.

RISPERDAL® CONSTA® 37,5 mg prolonged release suspension for intramuscular injection.

RISPERDAL® CONSTA® 50 mg prolonged release suspension for intramuscular injection.

COMPOSITION

RISPERDAL CONSTA contains 25 mg; 37,5 mg or 50 mg risperidone.

RISPERDAL CONSTA is an extended release microspheres formulation of risperidone, composed of

risperidone drug substance micro-encapsulated in polylactide-co-glycolide, at a concentration of 381

mg risperidone per gram of microspheres.

Inactive ingredients: The diluent contains Polysorbate 20, carmellose sodium 40mPa.s, disodium

hydrogen phosphate dihydrate, citric acid anhydrous, sodium chloride, sodium hydroxide, water for

injection.

PHARMACOLOGICAL CLASSIFICATION

A.2.6.5 Central nervous system depressants. Miscellaneous structures.


CCDS Jan 2013 of 56

PHARMACOLOGICAL ACTION

Pharmacodynamic properties

Risperidone is an antipsychotic of the benzisoxazol derivatives. It is a selective monoaminergic

antagonist. Risperidone has affinity for serotonin-5-HT2, dopamine-D2, H1-histamine, α1- and α2-

adrenergic receptors. Risperidone has no affinity for cholinergic receptors. It is a potent D2-

antagonist.

Pharmacokinetic properties

Risperidone is metabolised by cytochrome CYP2D6 to 9-hydroxy-risperidone, which has a similar

pharmacological activity to risperidone. Risperidone and 9-hydroxy-risperidone form the active

antipsychotic fraction. Another metabolic pathway of risperidone is N-dealkylation.

After a single intramuscular injection with RISPERDAL CONSTA the release profile consists of a

small initial release of risperidone (< 1 % of the dose), followed by a lag time of 3 weeks. Following

intramuscular injection the main release of risperidone starts from 3 weeks onwards is maintained

from 4 to 6 weeks and subsides by week 7.

The combination of the release profile and the dosage regimen (intramuscular injection every two

weeks) result in sustained therapeutic plasma concentrations. Therapeutic plasma concentrations

remain until 4 to 6 weeks after the last RISPERDAL CONSTA injection. The elimination phase is

complete approximately 7 to 8 weeks after the last injection.

The absorption of risperidone from RISPERDAL CONSTA is complete.

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 about

90 % and that of the active metabolite 9-hydroxy-risperidone is 77 %.


CCDS Jan 2013 of 56

The active antipsychotic fraction and risperidone clearances were 5,0 and 13,7 L/h in extensive

metabolisers, respectively, and 3,2 and 3,3 L/h in poor metabolisers of CYP2D6, respectively.

After repeated intramuscular injections with 25 or 50 mg RISPERDAL CONSTA every two weeks,

median trough and peak plasma concentrations of the active antipsychotic fraction fluctuated

between 9,9 - 19,2 ng/ml and 17,9 – 45,5 ng/ml respectively. The pharmacokinetics of risperidone

are linear in the dose range of 25 - 50 mg injected every 2 weeks. No accumulation of risperidone

was observed during long-term use (12 months) in patients who were injected with 25 - 50 mg every

two weeks.

A single dose study showed higher active plasma concentrations and a reduced clearance of the active

antipsychotic fraction by 30 % in the elderly and 50 % in patients with moderate renal insufficiency. In

patients with severe renal insufficiency the clearance was one third that of normal. The plasma

concentrations of risperidone were normal in patients with liver insufficiency, but the mean free fraction

of risperidone in plasma was increased by about 35 %.

INDICATIONS

RISPERDAL CONSTA is indicated for the treatment of acute and chronic schizophrenia. RISPERDAL

CONSTA is also indicated as monotherapy or adjunctive therapy for the maintenance treatment to

prevent the recurrence of manic episodes of bipolar I disorder in patients who have previously

responded to oral antipsychotics or other anti-manic treatments.

CONTRA-INDICATIONS

RISPERDAL CONSTA is contra-indicated in patients with known hypersensitivity to risperidone or

any of the components.

Not for children under 18 years as efficacy and safety in children under the age of 18 years have not

been studied.


CCDS Jan 2013 of 56

Hepatic and renal impairment

RISPERDAL CONSTA has not been studied in hepatically and renally impaired patients.

Parkinson’s disease and Lewy body dementia (see WARNINGS).

WARNINGS AND SPECIAL PRECAUTIONS

Elderly Patients with Dementia

Overall Mortality

Elderly patients with dementia treated with atypical antipsychotic medicines have an increased

mortality compared to placebo in a meta-analysis of 17 controlled trials of atypical antipsychotic

medicines, including risperidone. In placebo-controlled trials with oral risperidone in this population,

the incidence of mortality was 4,0 % for risperidone -treated patients compared to 3,1 % for placebo-

treated patients. The mean age (range) of patients who died was 86 years (range 67 -100).

Concomitant use with Furosemide

In the oral RISPERDAL 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.

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 should be considered prior to the decision to use.


CCDS Jan 2013 of 56

There was no increased incidence of mortality among patients taking other diuretics as concomitant

medication 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 Events (CAE)

In placebo-controlled trials in elderly patients with dementia, there was a higher incidence of

cerebrovascular adverse events, (cerebrovascular accidents and transient ischemic attacks),

including fatalities, in patients treated with oral risperidone compared to patients receiving placebo

(mean age 85 years; range 73 - 97).

Orthostatic Hypotension

Due to the alpha-blocking activity of RISPERDAL CONSTA, (orthostatic) hypotension can occur,

especially during the initial dose-titration period (see INTERACTIONS). RISPERDAL CONSTA

should be used with caution in patients with known cardiovascular disease, and the dosage should be

gradually titrated as recommended. A dose reduction should be considered if hypotension occurs.

Leukopenia, Neutropenia, and Agranulocytosis

Events of leucopenia, neutropenia and agranulocytosis have been reported with RISPERDAL

CONSTA. Agranulocytosis has been reported during post-marketing surveillance.

Patients with a history of a clinically significant low white blood cell count (WBC) or a medicine-

induced leukopenia/neutropenia should be monitored during therapy and discontinuation of

RISPERDAL CONSTA 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


CCDS Jan 2013 of 56

significant neutropenia (absolute neutrophil count < 1 X 109/L) should discontinue RISPERDAL

CONSTA and have their WBC followed until recovery.

Venous thromboembolism

Cases of venous thromboembolism (VTE) have been reported with RISPERDAL CONSTA. 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 RISPERDAL CONSTA and

preventive measures undertaken

Tardive Dyskinesia/Extrapyramidal Symptoms (TD/EPS)

RISPERDAL CONSTA has been associated with the induction of tardive dyskinesia (TD)

characterised by potentially irreversible rhythmical involuntary movements, predominantly of the

tongue and/or face. It has been reported that the occurrence of extrapyramidal symptoms is a risk

factor for the development of tardive dyskinesia. Tardive dyskinesia appears to be more prominent in

the elderly especially elderly females. RISPERDAL CONSTA has a potential to induce extrapyramidal

symptoms. If signs and symptoms of tardive dyskinesia appear, the discontinuation of RISPERDAL

CONSTA should be considered.

Neuroleptic Malignant Syndrome (NMS)

Neuroleptic Malignant Syndrome is a potentially fatal symptom complex, 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, all antipsychotic

medicines, including RISPERDAL CONSTA, should be discontinued.


CCDS Jan 2013 of 56

Parkinson’s disease/ Lewy body dementia and NMS

Patients with Parkinson’s Disease or Dementia with Lewy bodies (DLB) have an increased risk of

Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotic

medications (see CONTRA-INDICATIONS). Manifestation of this increased sensitivity can include

confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms.

In addition, in clinical trials, elderly patients have a higher mortality than placebo-treated patients.

Hyperglycaemia and diabetes mellitus:

Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or

death, has been reported in patients treated with RISPERDAL CONSTA.

Patients with an established diagnosis of diabetes mellitus who are started on RISPERDAL CONSTA

should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes

mellitus (e.g. obesity, family history of diabetes) who are starting treatment with RISPERDAL

CONSTA should be monitored for symptoms of hyperglycaemia including polydipsia, polyuria,

polyphagia, and weakness. Patients who develop symptoms of hyperglycaemia during treatment with

RISPERDAL CONSTA should undergo fasting blood glucose testing. In some cases,

hyperglycaemia has resolved when RISPERDAL CONSTA was discontinued: however, some

patients required continuation of anti-diabetic treatment despite discontinuation of RISPERDAL

CONSTA.

Weight gain

Significant weight gain has been reported. Monitoring weight gain is advisable when RISPERDAL

CONSTA is being used. Patients may be advised to refrain from overeating in view of the possibility of

weight gain.

QT Interval


CCDS Jan 2013 of 56

Caution should be exercised when RISPERDAL CONSTA is prescribed in patients with a history of

cardiac dysrhythmias, in patients with congenital long QT syndrome, and in concomitant use with

medicines known to prolong the QT interval.

Priapism

Medicines with alpha-adrenergic blocking effects have been reported to induce

priapism. Priapism has been reported with RISPERDAL during postmarketing

surveillance (see SIDE-EFFECTS AND SPECIAL PRECAUTIONS).

Body Temperature Regulation

Disruption of the body’s ability to reduce core body temperature may occur. Appropriate care is

advised when prescribing RISPERDAL CONSTA 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 medication 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.

Seizures

RISPERDAL CONSTA should be used cautiously in patients with a history of seizures or other

conditions that potentially lower the seizure threshold.

Intraoperative Floppy Iris Syndrome


CCDS Jan 2013 of 56

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in patients

treated with medicines with alpha1a-adrenergic antagonist effect, including RISPERDAL

CONSTA.

IFIS may increase the risk of eye complications during and after the operation. Current or past

use of RISPERDAL CONSTA should be made known to the ophthalmic surgeon in advance of

surgery. The potential benefit of stopping RISPERDAL CONSTA prior to cataract surgery has not

been established and must be weighed against the risk of stopping RISPERDAL CONSTA

therapy.

Administration

Care must be taken to avoid inadvertent injection of RISPERDAL CONSTA into a blood vessel.

For risperidone naive patients, it is recommended to establish tolerability with oral risperidone prior to

initiating treatment with RISPERDAL CONSTA.

Ability to drive or use machinery:

RISPERDAL CONSTA may impair mental alertness. Therefore patients should be advised not to

drive or operate machinery until their individual susceptibility is known.

INTERACTIONS:

The risk of using RISPERDAL CONSTA in combination with other medicines has not been

systematically evaluated.

Given the primary CNS depressive effect of RISPERDAL CONSTA, it should be used with caution in

combination with alcohol and other centrally acting medicines.

RISPERDAL may antagonise the effect of levodopa and other dopamine agonists.


CCDS Jan 2013 of 56

Clinically significant hypotension has been observed postmarketing with concomitant use of

risperidone and antihypertensive treatment (see WARNINGS AND SPECIAL PRECUTIONS).

Caution is advised when prescribing RISPERDAL CONSTA with medicines known to prolong the QT

interval.

Carbamazepine has been shown to decrease the plasma levels of the active antipsychotic fraction of

risperidone. Similar effects may be observed with other CYP3A4 hepatic enzyme inducers. On

discontinuation of carbamazepine or other hepatic enzyme inducers the dosage of RISPERDAL

CONSTA should be re-evaluated and, if necessary, decreased.

Fluoxetine and paroxetine, CYP2D6 inhibitors, increase the plasma concentration of risperidone but

less so of the active anti-psychotic fraction. When concomitant fluoxetine or paroxetine is initiated or

discontinued, the medical practitioner should re-evaluate the dosing of RISPERDAL CONSTA.

Venlafaxine administered under steady-state conditions at 150 mg/day slightly inhibited the CYP2D6-

mediated metabolism of risperidone (administered as a single 1 mg oral dose) to its active metabolite,

9-hydroxyrisperidone, resulting in an approximate 32 % increase in risperidone AUC. However,

venlafaxine co-administration did not significantly alter the pharmacokinetic profile of the total active

antipsychotic fraction.

Topiramate modestly reduced the bioavailability of risperidone, but not that of the active antipsychotic

fraction. Therefore, this interaction is unlikely to be of clinical significance.

Phenothiazines, tricyclic antidepressants and some beta-blockers may increase the plasma

concentration of risperidone but not those of the active antipsychotic fraction.

Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction.

Cimetidine and ranitidine increased the bioavailability of risperidone, but only marginally that of the

active antipsychotic fraction.

Erythromycin, a CYP3A4 inhibitor, does not change the pharmacokinetics of risperidone and the

active antipsychotic fraction.

The cholinesterase inhibitors, galantamine and donepezil, do not show a clinically relevant effect on

the pharmacokinetics of risperidone and the active antipsychotic fraction.


CCDS Jan 2013 of 56

When RISPERDAL CONSTA is taken together with other highly protein-bound medicines (e.g.

diazepam, warfarin, digitoxin, imipramine and propranolol), there is no clinically relevant displacement

of either agent from the plasma proteins.

RISPERDAL CONSTA does not show a clinically relevant effect on the pharmacokinetics of lithium,

valproate, digoxin or topiramate.

There is an increased mortality in elderly patients with dementia concomitantly receiving furosemide

and RISPERDAL CONSTA.

PREGNANCY AND LACTATION

Pregnancy:

The safety of RISPERDAL CONSTA for use in human pregnancy has not been established.

Although, in experimental animals, risperidone did not show direct reproductive toxicity, some

indirect, prolactin- and CNS-mediated effects were observed. No teratogenic effect of risperidone

was noted in any study.

Neonates exposed to antipsychotic medicines (including RISPERDAL CONSTA) during the third

trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms that may vary in

severity following delivery. These symptoms in the neonates may include agitation, hypertonia,

hypotonia, tremor, somnolence, respiratory distress, or feeding disorder.

Therefore, RISPERDAL CONSTA should only be used during pregnancy if the benefits outweigh the

risks.

Lactation:

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.

Therefore, women receiving RISPERDAL CONSTA should not breastfeed.


CCDS Jan 2013 of 56

DOSAGE AND DIRECTIONS FOR USE

For risperidone naive patients, it is recommended to establish tolerability with oral risperidone prior to

initiating treatment with RISPERDAL CONSTA.

When starting RISPERDAL CONSTA, the patient must receive an oral antipsychotic medicine

simultaneously for at least three weeks, as therapeutic concentrations of RISPERDAL CONSTA are

only reached after a three week period.

RISPERDAL CONSTA should be administered every two weeks by deep intramuscular gluteal

injection using the enclosed safety needle. For gluteal administration, use the 5,08 cm needle

alternating injections between the two buttocks. Do not administer intravenously (see WARNINGS

AND SPECIAL PRECAUTIONS and “Instructions for Use and Handling”).

Adults

The recommended dose is 25 mg intramuscular every two weeks. Some patients may benefit from

the higher doses of 37,5 mg or 50 mg. No additional benefit was observed with 75 mg in clinical trials

in patients with schizophrenia. Doses above 50 mg were not studied in patients with bipolar disorder.

Doses higher than 50 mg every 2 weeks are not recommended.

Upward dosage adjustment should not be made more frequently than every 4 weeks. The effect of

this dose adjustment should not be anticipated earlier than 3 weeks after the first injection with the

higher dose.

Elderly

The recommended dose is 25 mg intramuscular every two weeks.

Renal and hepatic impairment

RISPERDAL CONSTA has not been studied in hepatically and renally impaired patients.


CCDS Jan 2013 of 56

NEEDLE –FREE VIAL ACCESS DEVICE:

RISPERDAL® CONSTA® requires close attention to the step-by-step ‘Instructions for

Use’ to help ensure successful administration and help avoid difficulties in the use of

the kit.

RISPERDAL CONSTA powder in the vial must be reconstituted only in the diluent in

the syringe supplied in the dose pack, and must be administered with only the

appropriate needle supplied in the dose pack for gluteal (5,08 cm needle)

administration. Do not substitute any components in the dose pack. To assure that

the intended dose of risperidone is delivered the full contents from the vial must be

administered. Administration of partial contents may not deliver the intended dose of

risperidone It is recommended to administer immediately after reconstitution.

Remove the dose pack of RISPERDAL CONSTA from the refrigerator and allow it

to come to room temperature for approximately 30 minutes prior to reconstitution.

1. Flip off the plastic coloured cap from the vial. Do not remove the grey rubber stopper.

Wipe the top of the grey rubber stopper with an alcohol wipe and allow to dry.

2. Peel back the blister pouch and remove the SmartSite Needle-Free Vial Access Device by

holding between the white luer cap and the skirt.

Do not touch the spike tip of the access device at any time.


CCDS Jan 2013 of 56

3. It is very important that the SmartSite Needle-Free Access Device be placed on the

vial correctly or the diluents could leak upon transfer to the vial. Place the vial on a

hard surface. Orient the SmartSite Needle-Free Vial Access Device vertically over the vial

so that the spike tip is at the center of the vial’s rubber stopper.

With a straight downward push, press the spike tip of the SmartSite Needle-Free Access

Device through the center of the vial’s rubber stopper until the device securely snaps onto

the vial top.

Correct


CCDS Jan 2013 of 56

Incorrect

4. Hold the base of the vial and swab the syringe connection point (blue circle) of the

SmartSite Needle-Free Vial Access Device with an alcohol wipe and allow to dry prior to

attaching the syringe to the SmartSite Needle-Free Vial Access Device.

The prefilled syringe has a white tip consisting of 2 parts: a white collar and a smooth

white cap. To open the syringe, hold the syringe by the white collar and snap off the

smooth white cap (DO NOT TWIST OR CUT OFF THE WHITE CAP). Remove the white

cap together with the rubber tip cap inside.


CCDS Jan 2013 of 56

For all syringe assembly steps, hold the syringe only by the white collar located at the tip of

the syringe. Holding the white collar will help to prevent the white collar from getting

detached and ensure a good connection to the syringe. Be careful not to overtighten

components when assembling. Overtightening connections may cause syringe components

parts to loosen from the syringe body.

5. While holding the white collar of the syringe, insert and press the syringe tip into the blue

circle of the SmartSite Needle-Free Vial Access Device and twist in a clockwise motion to

secure the connection of the syringe to the SmartSite Needle-Free Vial Access Device

(avoid over-twisting).

Hold the skirt of the SmartSite Needle-Free Vial Access Device during attachment to

prevent it from spinning.

Keep the syringe and the SmartSite Needle-Free Vial Access Device aligned.

6. Inject the entire contents of the syringe containing the diluent into the vial.


CCDS Jan 2013 of 56

7. Shake the vial VIGOROUSLY while holding the plunger rod down with the thumb, shake

the vial vigorously for a minimum of 10 seconds to ensure a homogeneous suspension.

When properly mixed, the suspension appears uniform, thick, and milky in colour. The

microspheres will be visible in liquid but no dry microspheres remain.

DO NOT STORE THE VIAL AFTER RECONSTITUTION OR THE SUSPENSION

MAY SETTLE.

8. Invert the vial completely and SLOWLY withdraw the entire contents of the suspension

from the vial into the syringe.

Tear the section of the vial label at the perforation and apply the detached label to the

syringe for identification purposes.

9. While holding the white collar of the syringe, unscrew the syringe from the SmartSite

Needle-Free Vial Access Device. Discard the vial and the vial access device appropriately.


CCDS Jan 2013 of 56

10. Open the needle pack and select the appropriate needle provided with the kit. Do NOT

touch the connection part of the needle, only touch the transparent sheath of the needle:

For GLUTEAL injection, select the 20G TW 5,08 cm needle (longer needle with yellow

coloured hub).

11. To prevent contamination, be careful not to touch the orange Needle-Pro safety device’s

luer connection. While holding the white collar of the syringe, attach the luer connection

of the orange Needle-Pro safety device to the syringe with an easy clockwise twisting

motion.


CCDS Jan 2013 of 56

12. While continuing to hold the white collar of the syringe, grasp the transparent needle

sheath and seat the needle firmly on the orange Needle-Pro® safety device with a push

and a clockwise twist. Seating the needle will help ensure a secure connection

between the needle and the orange Needle-Pro safety device while conducting the

following steps.

13. RESUSPENSION OF RISPERDAL CONSTA WILL BE NECESSARY PRIOR

TO ADMINISTRATION AS SETTLING WILL OCCUR OVER TIME ONCE

PRODUCT IS RECONSTITUTED. RESUSPEND THE MICROSPHERES IN THE

SYRINGE BY SHAKING VIGOROUSLY.

14. While holding the white collar of the syringe, pull the transparent needle sheath straight

away from the needle. DO NOT TWIST the sheath as the luer connections may be

loosened.

15. Tap the syringe gently to make any air bubbles rise to the top.


CCDS Jan 2013 of 56

Remove air in syringe by depressing the plunger rod, carefully and slowly while holding

the needle in an upright position. Inject the entire contents of the syringe intramuscularly

into the selected gluteal muscle of the patient immediately. Gluteal injection should be

made into the upper-outer quadrant of the gluteal area.

DO NOT ADMINISTER INTRAVENOUSLY.

WARNING: To avoid a needle stick injury with a contaminated needle:

Do not use free hand to press the Needle-Pro® safety device over the needle.

Do not intentionally disengage the Needle-Pro® safety device.

Do not attempt to straighten the needle or engage the Needle-Pro® device if the needle

is bent or damaged.

Do not mishandle the Needle-Pro® safety device as it may cause the needle to protrude

from the Needle-Pro® safety device.

16. After injection is complete, press the needle into the orange Needle-Pro® safety device

using a one-handed technique. Perform a one-handed technique by GENTLY pressing

the orange Needle-Pro® safety device against a flat surface. AS THE ORANGE NEEDLE-

PRO® SAFETY DEVICE IS PRESSED, THE NEEDLE WILL FIRMLY ENGAGE INTO THE

ORANGE NEEDLE-PRO® SAFETY DEVICE. Visually confirm that the needle is fully

engaged into the orange Needle-Pro® safety device before discarding. Discard needle

appropriately.


CCDS Jan 2013 of 56

Do Not Reuse: Medical devices require specific material characteristics to perform as intended.

These characteristics have been verified for single use only. Any attempt to re-process the device for

subsequent re-use may adversely affect the integrity of the device or lead to deterioration in

performance.

SIDE-EFFECTS

Clinical trial data

The most frequently reported adverse drug reactions (ADR’s) (incidence 1/10) are: Insomnia, anxiety,

headache, upper respiratory tract infection, Parkinsonism, depression, and akathisia.

The following are all the ADR’s that were reported in 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), and not known (cannot be estimated

from the available clinical trial data).

Within each frequency grouping, undesirable effects are presented in order of decreasing

seriousness.

Investigations

Common: Abnormal electrocardiogram, increaseda blood prolactin, increased

blood glucose, increased hepatic enzyme, increased transaminases,


CCDS Jan 2013 of 56

increased gamma-glutamyltransferase, increased weight, decreased

weight.

Uncommon Prolonged electrocardiogram QT.

Cardiac disorders

Common Atrioventricular block, tachycardia.

Uncommon Bundle branch block, bradycardia, sinus bradycardia, palpitations.

Blood and lymphatic system disorders

Common Anaemia

Uncommon Neutropenia

Nervous system disorders

Very common Parkinsonismb, akathisiab, headache.

Common Dizziness, sedation, somnolence, tremor, dystoniab, tardive

dyskinesia, dyskinesiab.

Uncommon Convulsion, syncope, dizziness postural, hypoaesthesia,

paraesthesia, lethargy, hypersomnia.

Eye disorders

Common Blurred vision, conjunctivitis.

Ear and labyrinth disorders

Common Vertigo.

Uncommon Ear pain.


CCDS Jan 2013 of 56

Respiratory, thoracic and mediastinal disorders

Common Dyspnoea, cough, nasal congestion, pharyngolaryngeal pain.

Gastrointestinal disorders

Common Vomiting, diarrhoea, constipation, nausea, abdominal pain,

dyspepsia, toothache, dry mouth, stomach discomfort, gastritis.

Renal and urinary disorders

Common Urinary incontinence.

Uncommon Urinary retention.

Skin and subcutaneous tissue disorders

Common Rash, eczema.

Uncommon Pruritus, acne, dry skin.

Musculoskeletal and connective tissue disorders

Common Arthralgia, back pain, pain in extremity, myalgia.

Uncommon Muscular weakness, neck pain, buttock pain, musculoskeletal chest

pain.

Metabolism and nutrition disorders

Common Hyperglycaemia.

Uncommon Increased appetite, decreased appetite.

Infections and infestations

Very common Upper respiratory tract infection.

Common Pneumonia, influenza, lower respiratory tract infection, bronchitis,


CCDS Jan 2013 of 56

urinary tract infection, ear infection, sinusitis, viral infection,

rhinitus, pharyngitis.

Uncommon Cystitis, gastroenteritis, infection, localised infection, subcutaneous

abscess.

Injury, poisoning and procedural complications

Common Fall

Uncommon Injection site pain.

Vascular disorders

Common Hypertension, hypotension.

Uncommon Orthostatic hypotension.

General disorders and administration site conditions

Common Pyrexia, peripheral oedema, chest pain, fatigue, pain, injection site

pain, asthenia, influenza like illness, malaise.

Uncommon Injection site induration, induration, chest discomfort, sluggishness,

feeling abnormal.

Immune system disorders

Uncommon Hypersensitivity.

Reproductive system and breast disorders

Common Amenorrhoea, erectile dysfunction, galactorrhoea, oligomenorrhea,

breast discomfort, ejaculation disorder.

Uncommon Sexual dysfunction, gynaecomastia.


CCDS Jan 2013 of 56

Psychiatric disorders

Very common Depression, insomnia, anxiety.

Common Agitation, sleep disorder.

Uncommon Decreased libido, nervousness.

a) Hyperprolactinemia can in some cases lead to gynaecomastia, menstrual

disturbances, amenorrhoea, and galactorrhea.

b) Extrapyramidal disorder may occur: Parkinsonism (salivary hypersecretion,

musculoskeletal stiffness, Parkinsonism, drooling, cogwheel rigidity, bradykinesia,

hypokinesia, masked facies, muscle tightness, akinesia, nuchal rigidity, muscle

rigidity, Parkinsonian gait, and glabellar reflex abnormal), akathisia (akathisia,

restlessness, hyperkinesia, and restless leg syndrome), tremor, dyskinesia

(dyskinesia, muscle twitching, choreoathetosis, athetosis, and myoclonus),

dystonia. Dystonia includes dystonia, muscle spasms, hypertonia, torticollis, muscle

contractions involuntary, muscle contracture, blepharospasm, oculogyration,

tongue paralysis, facial spasm, laryngospasm, myotonia, opisthotonus,

oropharyngeal spasm, pleurothotonus, tongue spasm, and trismus. Tremor

includes tremor and Parkinsonian rest tremor. It should be noted that a broader

spectrum of symptoms are included, that do not necessarily have an

extrapyramidal origin.

Postmarketing Data

Adverse events first identified as adverse reactions during postmarketing experience with

RISPERDAL CONSTA.

Blood and Lymphatic Disorders


CCDS Jan 2013 of 56

Agranulocytosis, thrombocytopenia.

Endocrine Disorders

Inappropriate antidiuretic hormone secretion.

Metabolism and Nutrition Disorders

Diabetic ketoacidosis, diabetes mellitus, hypoglycaemia, water intoxication, increased blood

cholesterol, increased blood triglycerides.

Psychiatric Disorders

Mania.

Nervous System Disorders

Dysgeusia.

Eye Disorders

Retinal artery occlusiona.

Floppy iris syndrome (intraoperative)

Cardiac Disorders

Atrial fibrillation.

Vascular Disorders

Deep vein thrombosis, pulmonary embolism.

Respiratory, Thoracic, and Mediastinal Disorders

Sleep apnoea syndrome.

Gastrointestinal Disorders

Pancreatitis.

Paralytic Ileus

Hepatobiliary Disorders

Jaundice.

Skin and Subcutaneous Tissue Disorders

Angioedema, alopecia.

Renal and Urinary Disorders


CCDS Jan 2013 of 56

Urinary retention.

Pregnancy, Puerperium and Perinatal Conditions

Neonatal drug withdrawal syndrome.

Reproductive System and Breast Disorders

Priapism.

General Disorders

Hypothermia, injection site abscess, injection site cellulites, injection site cyst, injection site

haematoma, injection site necrosis, injection site ulcer.

a RISPERDAL CONSTA formulation only, reported in the presence of an intracardiac defect predisposing to a right-to-left shunt (e.g., a patent foramen ovale)

Hypersensitivity

Cases of anaphylactic reaction after injection with RISPERDAL® CONSTA® have been reported

during postmarketing experience in patients who have previously tolerated oral risperidone.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT

Symptoms:

Reported signs and symptoms have been those resulting from an exaggeration of the medicines

known pharmacological effects. Symptoms of acute overdosage include drowsiness, sedation,

hypotension, tachycardia and extrapyramidal symptoms. In overdose, QT-prolongation and

convulsions have been reported. Torsades de pointes has been reported in association with

combined overdose of oral RISPERDAL and paroxetine. In the case of acute overdosage, the

possibility of multiple medicine involvement should be considered.

Treatment:


CCDS Jan 2013 of 56

Establish and maintain a clear airway and ensure adequate oxygenation and ventilation.

Cardiovascular monitoring should commence immediately and should include continuous

electrocardiographic monitoring to detect possible dysrhythmias.

Since there is no known antidote if accidental poisoning or overdosage is suspected, 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, anticholinergic medication should be administered. Close medical

supervision and monitoring should continue until the patient recovers.

IDENTIFICATION

Clear, colourless, glass vial with a grey rubber stopper, tightly crimped, coloured flip-off cap*

containing a white, free flowing powder, free from visible foreign material, suspending readily without

clumping or visible foreign material.

* The colour of the flip-off cap is verified- the colour varies by dosage strengths as follows:

Pink: 25 mg risperidone per vial

Green: 37,5 mg risperidone per vial

Blue: 50 mg risperidone per vial

Pre-filled syringe of diluent for reconstitution.

Clear, colourless, aqueous solution free from visible foreign materials.

PRESENTATION

Needle-free Vial Access Device:

- One 5 ml vial containing RISPERDAL CONSTA powder for suspension for injection.

- One AlarisTM SmartSite® Needle-free Vial Access Device for reconstitution.

- One 3 ml prefilled syringe containing 2 ml diluent for RISPERDAL CONSTA.


CCDS Jan 2013 of 56

- One needle for intramuscular injection ( a 20G TW 5.08 cm safety needle with Needle-Pro safety

device for gluteal administration). (“Rx- only”=device to be sold with prescription medicines only).

STORAGE INSTRUCTIONS

The entire dose pack should be stored in the refrigerator (2 - 8 °C.) and protected from light. It

should not be exposed to temperatures above 25 °C.

If refrigeration is unavailable, RISPERDAL CONSTA can be stored at temperatures not exceeding

25 °C., for no more than 7 days prior to administration. Do not expose unrefrigerated product to

temperatures above 25 °C.

KEEP OUT OF REACH OF CHILDREN.


CCDS Jan 2013 of 56

REGISTRATION NUMBER

RISPERDAL CONSTA 25, 37,5 & 50 mg: 37/2.6.5/0142 – 4

Nam. Reg. No.:

RISPERDAL CONSTA 25, 37,5 & 50 mg:

06/2.6.5/0023/4/5

NS 3

NAME AND BUSINESS ADDRESS OF THE APPLICANT

JANSSEN PHARMACEUTICA (PTY) LTD

(Reg. No.: 1980/011122/07)

Building 6, Country Club Estate, 21 Woodlands Drive, Woodmead, 2191

Tel: +27 (11) 518 7000

www.janssen.co.za

DATE OF PUBLICATION OF THE PACKAGE INSERT

28 November 2014

http://www.janssen.co.za/


CCDS Jan 2013 of 56

VOUBILJET

SKEDULERINGSTATUS

Skedule 5.

EIENDOMSNAAM EN DOSEERVORM

RISPERDAL® CONSTA® 25 mg langwerkende vrystelling suspensie vir intramuskulêre inspuiting.

RISPERDAL® CONSTA® 37,5 mg langwerkende vrystelling suspensie vir intramuskulêre inspuiting.

RISPERDAL® CONSTA® 50 mg langwerkende vrystelling suspensie vir intramuskulêre inspuiting.

SAMESTELLING

RISPERDAL CONSTA bevat 25 mg; 37,5 mg of 50 mg risperidoon.

RISPERDAL CONSTA is ’n verlengde vrystelling mikrosfeer-formulering met risperidoon, saamgestel

uit risperidoon geneesmiddel substans, wat gemikroënkapsuleer is met poliaktied ko-glikolied, by ’n

konsentrasie van 381 mg risperidoon per gram mikrosfere.

Onaktiewe bestanddele: Die verdunningsmiddel bevat polisorbaat-20, natriumkarmellose 40 mPa.s,

dinatriumwaterstoffosfaat-dihidraat, watervrye sitroensuur, natriumchloried, natriumhidroksied, water

vir inspuiting.

FARMAKOLOGIESE KLASSIFIKASIE

A.2.6.5 Sentrale senuweestelsel depressante. Diverse strukture.

FARMAKOLOGIESE WERKING

Farmakodinamiese eienskappe

Risperidoon is ŉ antipsigotiese middel van die bensisoksasoolderivate. Dit is ŉ selektiewe mono-

aminergiese antagonis. Risperidoon toon ŉ affiniteit vir serotonien-5HT2, dopamien-D2, H1-histamien

en α1- en α2-adrenergiese reseptore. Risperidoon besit geen affiniteit vir cholinergiese reseptore nie.

Dit is ŉ kragtige D2-antagonis.

Farmakokinetiese eienskappe

Risperidoon word deur sitochroom CYP2D6 na 9-hidroksierisperidoon, wat ’n soortgelyke

farmakologiese aktiwiteit as risperidoon het, gemetaboliseer. Risperidoon en 9-hidroksierisperidoon

vorm die aktiewe antipsigotiese fraksie. ’n Ander metaboliese baan van risperidoon is N-dealkilering.


CCDS Jan 2013 of 56

Na ’n enkele intramuskulêre inspuiting met RISPERDAL CONSTA bestaan die vrystellingsprofiel uit

’n geringe aanvanklike vrystelling van risperidone (< 1 % van die dosis), gevolg deur ’n sloertydperk

van 3 weke. Na intramuskulêre inspuiting begin die hoof vrystelling van risperidoon na 3 weke, word

volgehou vir 4 tot 6 weke en neem af teen week 7.

Die kombinasie van die vrystellingsprofiel en die doseringsregimen (intramuskulêre inspuiting elke

twee weke) het gelei tot volgehoue terapeutiese plasmakonsentrasies. Terapeutiese

plasmakonsentrasies is volgehou vir 4 tot 6 weke na die laaste RISPERDAL CONSTA inspuiting. Die

eliminasiefase was volledig, ongeveer 7 tot 8 weke na die laaste inspuiting.

Die absorpsie van risperidoon uit RISPERDAL CONSTA is volledig.

Risperidoon word vinnig versprei. Die verspreidingsvolume is 1 - 2 L/kg. In plasma word risperidoon

aan albumien en alfa-1-suur glikoproteïen gebind. Die plasma-proteïenbinding van risperidoon is

ongeveer 90 % en dié van die aktiewe metaboliet 9-hidroksie-risperidoon is 77 %.

Die aktiewe antipsigotiese fraksie en risperidoon opklaring was onderskeidelik 5,0 en 13,7 L/h by

omvangryke metaboliseerders en 3,2 en 3,3 L/h by swak metaboliseerders van CYP2D6.

Na herhaalde intramuskulêre inspuitings met 25 of 50 mg RISPERDAL CONSTA elke twee weke, het

die mediane trog en piek plasmakonsentrasies van die aktiewe antipsigotiese fraksie gewissel tussen

onderskeidelik 9,9-19,2 ng/ml en 17,9 – 45,5 ng/ml. Die farmakokinetika van risperidoon is lineêr

binne die dosis reikwydte van 25 - 50 mg, elke 2 weke ingespuit. Geen akkumulasie van risperidoon

is met langtermyn gebruik (12 maande) by pasiënte wat met 25 - 50 mg elke twee weke ingespuit is

waargeneem nie.

’n Enkeldosis studie het hoër aktiewe plasmakonsentrasies en ’n afname in die suiwering van die

aktiewe antipsigotiese fraksie van 30 % in bejaardes en 50 % in pasiënte met matig ontoereikende

nierfunksie getoon. In pasiënte met erg ontoereikende nierfunksie was die suiwering een derde van

normaal. Die plasmakonsentrasies van risperidoon was normaal in pasiënte met ontoereikende

lewerfunksie. Die gemiddelde vrye fraksie van risperidoon in plasma was egter 35 % hoër.

INDIKASIES

RISPERDAL CONSTA word aangedui vir die behandeling van akute en chroniese skisofrenie.


CCDS Jan 2013 of 56

As monoterapie en ook as aanvullende behandeling vir instandhoudingsterapie om herhaling van

maniese episodes van Tipe I - bipolêre versteuring te voorkom by pasiënte wat voorheen gereageer

het op orale antipsigotika of ander anti-maniese behandelings.

KONTRA-INDIKASIES

RISPERDAL CONSTA word teenaangedui by pasiënte met ’n bekende oorgevoeligheid vir

risperidoon of enige van die komponent.

Dit is nie bedoel vir kinders onder 18 jaar nie, aangesien doeltreffendheid en veiligheid nie bestudeer

is by kinders onder 18 jaar oud nie.

Lewer- en nierinkorting

RISPERDAL CONSTA is nie bestudeer by pasiënte met ingekorte lewer- en nierfunksie nie.

Parkinson se siekte en Lewy-liggaam demensie (sien WAARSKUWINGS EN SPESIALE

VOORSORGMAATRËELS).

WAARSKUWINGS EN SPESIALE VOORSORGMAATRËELS

Bejaarde pasiënte met demensie

Algehele mortaliteit

In vergelyking met ŉ plasebo in ŉ meta-ontleding van 17 beheerde proewe met atipiese

antipsigotiese middels, insluitende risperidoon, het bejaarde pasiënte met demensie ’n toename in

mortaliteit getoon. In plasebobeheerde proewe met mondelikse risperidoon in hierdie populasie, was

die insidens van mortaliteit 4,0 % vir risperidoon -behandelde pasiënte in vergelyking met 3,1 % vir

plasebobehandelde pasiënte. Die gemiddelde ouderdom (reikwydte) van pasiënte wat gesterf het

was 86 jaar (reikwydte 67 – 100).

Gelyktydige gebruik saam met furosemied (sien INTERAKSIES).

In die mondelikse RISPERDAL plasebobeheerde studies in bejaarde pasiënte met demensie, is ŉ

groter insidens van mortaliteit in pasiënte wat met furosemied plus risperidoon behandel is (7,3 %;

gemiddelde ouderdom 89 jaar, reikwydte 75 – 97) waargeneem, in vergelyking met behandel met

risperidoon alleen (3,1 %; gemiddelde 84 jaar, reikwydte 70 – 96) of furosemied alleen (4,1 %;

gemiddelde ouderdom 80 jaar, reikwydte 67 – 90). Die toename in mortaliteit in pasiënte wat met

furosemied en risperidoon behandel is, is in twee van die vier kliniese proewe waargeneem.


CCDS Jan 2013 of 56

Daar is geen patofisiologiese meganisme geïdentifiseer om hierdie bevinding te verklaar nie, en daar

is ook nie ŉ konsistente patroon vir die oorsaak van dood waargeneem nie. Desnieteenstaande

behoort sorg aan die dag gelê te word en behoort die risiko en voordele van hierdie kombinasie

oorweeg te word voordat daar besluit word om dit te gebruik. Daar was geen toename in die insidens

van mortaliteit onder pasiënte wat ander diuretika as meegaande medikasie saam met risperidoon

geneem het nie. Ongeag die behandeling is dehidrasie ŉ algehele risikofaktor vir mortaliteit en

behoort daarom noukeurig in bejaarde pasiënte met demensie vermy te word.

Serebrovaskulêre newe-effekte (SNE)

In plasebobeheerde proewe in bejaarde pasiënte met demensie, was daar ŉ groter insidens van

serebrovaskulêre newe-effekte, (serebrovaskulêre toevalle en verbygaande iskemiese aanvalle),

insluitende fataliteite (gemiddelde ouderdom 85 jaar; reikwydte 73 – 97), in pasiënte wat met

mondelikse risperidoon behandel is, teenoor pasiënte wat ŉ plasebo ontvang het.

Ortostatiese hipotensie:

Weens die alfa-blokkerende werking van RISPERDAL CONSTA kan (ortostatiese) hipotensie

voorkom, veral gedurende die aanvanklike dosis-titrasie tydperk (sien Interaksies). RISPERDAL

CONSTA moet met sorg by pasiënte met bekende kardiovaskulêre siekte gebruik word en die dosis

moet geleidelik, soos aanbeveel, getitreer word. ŉ Dosisvermindering moet oorweeg word indien

hipotensie voorkom.

Leukopenie, neutropenie en agranulositose

Voorvalle van leukopenie, neutropenie en agranulositose is met RISPERDAL CONSTA aangemeld.

Agranulositose is met na-bemarkingsbewaking aangemeld.

Pasiënte met ’n geskiedenis van ’n klinies-beduidende lae witbloedseltelling (WBT), of

leukopenie/neutropenie veroorsaak deur medisyne, moet gedurende die behandeling gemoniteer

word en staking van RISPERDAL CONSTA moet oorweeg by die eerste tekens van ’n klinies-

beduidende afname in WBT wanneer ander oorsaaklike faktore afwesig is.

Pasiënte met klinies beduidende neutropenie moet deeglik gemoniteer word vir koors of ander

simptome of tekens van infeksie en moet sonder versuim behandel word indien sulke simptome of

tekens voorkom. Pasiënte met beduidende neutropenie (absolute neutrofieltelling < 1 X 109/L) moet

RISPERDAL CONSTA staak en hulle WBS moet nagegaan word totdat hulle herstel het.

Veneuse tromboëmbolisme


CCDS Jan 2013 of 56

Gevalle van veneuse tromboëmbolisme (VTE) is met RISPERDAL CONSTA aangemeld. Aangesien

pasiënte wat met antipsigotika behandel word dikwels presenteer met verworwe risikofaktore vir VTE,

moet alle moontlike risikofaktore vir VTE voor en tydens behandeling met RISPERDAL CONSTA

bepaal word en voorkomende maatreëls onderneem word.

Tardiewe diskinesie/ Ekstrapiramidale simptome (TD/EPS)

RISPERDAL CONSTA is geassosieer met die induksie van tardiewe diskinese, wat gekenmerk word

deur moontlik onomkeerbare ritmiese onwillekeurige bewegings, veral van die tong en/of gesig. Daar

is berig dat die voorkoms van ekstrapiramidale simptome ’n risikofaktor is vir die ontwikkeling van

tardiewe diskinese. Dit lyk of tardiewe diskinese meer prominent voorkom by bejaardes, veral

bejaarde vrouens. RISPERDAL CONSTA het die potensiaal om ekstrapiramidale simptome te

induseer. Indien tekens en simptome van tardiewe diskinese voorkom, moet staking van RISPERDAL

CONSTA oorweeg word.

Neuroleptiese Maligne Sindroom (NMS)

Neuroleptiese Maligne Sindroom (NMS) is ’n potensieël noodlottige simptoomkompleks, gekenmerk

deur hipertermie, spierstyfheid, outonome onstabiliteit, veranderde bewussyn en verhoogde serum

kreatinien-fosfokinase vlakke, is met antipsigotika gerapporteer. Ander tekens kan mioglobienurie

(rabdomiolise) en akute nierversaking insluit. Indien dit sou voorkom, moet alle antipsigotiese

middels, insluitende RISPERDAL, CONSTA gestaak word.

Parkinson’s se siekte/ Lewy liggaam demensie en NMS

Pasiënte met Parkinson se siekte of Demensie met Lewyliggame (DLL) is onderworpe aan ’n hoër

risiko vir Neuroleptiese Maligne Sindroom, asook verhoogde sensitiwiteit vir antipsigotiese

medikasies (sien KONTRA-INDIKASIES). Die manifestering van hierdie toename in sensitiwiteit kan

bo en behalwe ekstrapiramidale simptome, ook verwardheid, afstomping, posturale onstabiliteit,

waartydens die pasiënt dikwels val, insluit.

Daarbenewens het bejaarde pasiënte in kliniese proewe ’n hoër mortaliteit getoon as plasebo-

behandelde pasiënte.

Hiperglukemie en diabetes mellitus:

Hiperglukemie, in sommige gevalle ekstreem en geassosieer met keto-asidose of hiperosmolare

koma of dood, is in pasiënte wat met RISPERDAL CONSTA behandel is, aangemeld.

Pasiënte met ŉ bevestigde diagnose van diabetes mellitus en wie op RISPERDAL CONSTA begin

word, behoort gereeld vir verergering van glukosebeheer gemonitor te word. Pasiënte met


CCDS Jan 2013 of 56

risikofaktore vir diabetes mellitus (bv. Vetsug, familiegeskiedenis van diabetes mellitus) wat

behandeling met RISPERDAL CONSTA begin, behoort vir simptome van hiperglukemie, insluitende

polidipsie, poliurie, polifagie en swakheid gemonitor te word. Pasiënte wat simptome van

hiperglukemie gedurende die behandeling met RISPERDAL CONSTA ontwikkel, behoort ’n

vastende glukosetoets te ondergaan. In sommige gevalle het die hiperglukemie met staking van

RISPERDAL CONSTA verdwyn: sommige pasiënte het egter voortsetting van hul antidiabetiese

behandeling, ten spyte van onttrekking van RISPERDAL CONSTA, vereis.

Gewigstoename

Beduidende toename in gewig is aangemeld. Monitering van gewigstoename word aangeraai wanneer

RISPERDAL CONSTA gebruik word. Pasiënte kan aangeraai word om nie te veel te eet nie as gevolg

van die moontlikheid van gewigstoename.

QT- Interval

Versigtigheid moet uitgeoefen word as RISPERDAL CONSTA aan pasiënte met ’n geskiedenis van

kardiale disritmie, kongenitale lang-QT-sindroom en by dié wat geneesmiddels gebruik met bekende

vermoë om die QT-interval te verleng, voorgeskryf word.

Priapisme

Daar is berig dat medisyne met alfa-adrenergiese blokkerende uitwerking priapisme induseer.

Priapisme is aangemeld met risperidoon tydens nabemarkingstoesig (sien NEWE-EFFEKTE EN

SPESIALE VOORSORGMAATREËLS).

Liggaamstemperatuurbeheer

Versteuring in die vermoë van die liggaam om die kern-liggaamstemperatuur te verlaag kan

voorkom. Gepaste versorging word aangeraai wanneer RISPERDAL CONSTA voorgeskryf word

aan pasiënte wat toestande sal ervaar wat kan bydra tot ’n verhoging in kern-liggaamstemperatuur,

bv. strawwe oefening, blootstelling aan buitensporige hitte, gepaardgaande medikasie ontvang met

anticholinergiese werking, of onderhewig aan dehidrasie.

Antiëmetiese werking


CCDS Jan 2013 of 56

’n Antiëmetiese uitwerking is waargeneem in prekliniese navorsingstudies met risperidoon. Hierdie

effek, indien dit by die mens voorkom, kan die tekens en simptome van oordosering met sekere

medisyne of toestande soos inwendige obstruksie, Reye-sindroom en breintumor verbloem.

Toevalle

RISPERDAL CONSTA moet met omsigtigheid gebruik word by pasiënte met ’n geskiedenis van

toevalle of ander toestande wat moontlik die konvulsiedrempel kan verlaag.

Intra-operatiewe slap-iris-sindroom

Intra-operatiewe slap-iris-sindroom (ISIS) is tydens katarakoperasies waargeneem by pasiënte wat

met medisyne met alfa-1a-adrenergiese antagonistiese uitwerking, insluitende RISPERDAL

CONSTA, behandel is (sien NEWE-EFFEKTE).

ISIS kan die risiko van oogkomplikasies tydens en na die operasie verhoog. Huidige of vorige gebruik

van RISPERDAL CONSTA moet voor die operasie aan die oogchirurg bekend gemaak word. Die

moontlike voordele om RISPERDAL CONSTA behandeling voor die katarakoperasie te staak, is nie

vasgestel nie en moet opgeweeg word aan die risiko om die RISPERDAL CONSTA behandeling te

staak.

Toediening

Sorg moet geneem word om nie per abuis RISPERDAL CONSTA in ’n bloedvat in te spuit nie

Daar word aanbeveel dat verdraagbaarheid vir risperidoon eers met orale risperidoon by risperidoon-

naïewe pasiënte bepaal word voordat behandeling met RISPERDAL CONSTA begin word.

Vermoë om te bestuur of masjinerie te bedryf:

RISPERDAL CONSTA kan verstandelike wakkerheid aantas. Gevolglik moet pasiënte aangeraai

word om nie te bestuur of masjinerie te hanteer totdat hulle individuele vatbaarheid bekend is nie.

INTERAKSIES

Die risiko om RISPERDAL CONSTA in kombinasie met ander medisyne te gebruik is nie sistematies

bepaal nie.


CCDS Jan 2013 of 56

Vanweë die primêre SSS-onderdrukkende effek van RISPERDAL CONSTA, moet daar versigtigheid

aan die dag gelê word met die gesamentlike gebruik met alkohol of ander sentraalwerkende

geneesmiddels.

RISPERDAL kan die effek van levodopa en ander dopamien-agoniste antagoniseer.

Klinies-beduidende hipotensie is ná bemarking met die gesamentlike gebruik van risperidoon en

antihipertensiewe behandeling waargeneem (sien WAARSKUWINGS EN SPESIALE

VOORSORGMAATRËELS).

Versigtigheid word aangeraai wanneer RISPERDAL CONSTA saam met medisyne wat die QT-

interval verleng, voorgeskryf word.

Daar is aangetoon dat karbamasepien die plasmavlakke van die aktiewe antipsigotiese fraksie van

risperidoon verlaag. Soortgelyke effekte kan met ander CYP3A4-lewerensieminduseerders

waargeneem word. Met staking van karbamasepien of ander lewerensiem-induseerders moet die

dosis van RISPERDAL CONSTA herevalueer word en indien nodig, verminder word.

Fluoksetien en paroksetien, CYP 2D6- inhibeerders, verhoog die plasmakonsentrasie van

risperidoon, maar tot ‘n mindere mate die aktiewe antipsigotiese fraksie. Wanneer gesamentlik

toegediende fluoksetien of paroksetien geïnisieer of onttrek word, moet die geneesheer die dosering

van RISPERDAL CONSTA herevalueer.

Venlafaksien, 150 mg/dag onder bestendige toestande toegedien, het die CYP2D6-bemiddelde

metabolisme van risperidoon (as ’n enkele 1 mg orale dosis toegedien) tot die 9-hidroksierisperidoon

aktiewe metaboliet daarvan, effens inhibeer, met ’n gevolglike toename van 32 % in risperidoon-AOK.

Gesamentlike toediening van venlafaksien het egter nie die farmakokinetiese profiel van die totale

aktiewe antipsigotiese fraksie beduidend verander nie.

Topiramaat het die biobeskikbaarheid van risperidoon matig verminder, maar nie dié van die aktiewe

antipsigotiese fraksie nie. Daarom is dit onwaarskynlik dat hierdie interaksie van kliniese belang is.

Fenotiasiene, trisikliese antidepressante en sommige betablokkeerders kan die plasmakonsentrasie

van risperidoon laat toeneem, maar nie dié van die aktiewe antipsigotiese fraksie nie.

Amitriptilien affekteer nie die farmakokinetika van risperidoon of die aktiewe antipsigotiese fraksie nie.

Simetidien en ranitidien het die biobeskikbaarheid van risperidoon verhoog, maar het die

antipsigotiese fraksie slegs tot ’n geringe mate beïnvloed.


CCDS Jan 2013 of 56

Eritromisien, ’n CYP 3A4 inhibeerder, verander nie die farmakokinetika van risperidoon en die

aktiewe antipsigotiese fraksie nie.

Die cholienesterase inhibeerders, galantamien en donepesil, toon nie ’n klinies beduidende effek op

die farmakokinetika van risperidoon en die aktiewe antipsigotiese fraksie nie. Wanneer RISPERDAL

CONSTA saam met ander hoogs proteïengebonde geneesmiddels geneem word (bv. diasepam,

warfarien, digitoksien, imipramien en propranolol), is daar geen klinies relevante verplasing van enige

van hierdie middels vanaf die plasmaproteïene nie.

RISPERDAL CONSTA toon nie ’n klinies relevante effek op die farmakokinetika van litium, valproaat,

digoksien of topiramaat nie.

Daar is ’n verhoogde mortaliteit by bejaarde pasiënte met demensie, wat furosemied en RISPERDAL

CONSTA gesamentlik ontvang.

SWANGERSKAP EN LAKTASIE

Swangerskap:

Die veiligheid van RISPERDAL CONSTA tydens swangerskap is nie bepaal nie.

Alhoewel risperidoon nie in proefdiere direkte reproduktiewe toksisiteit getoon het nie, is sommige

indirekte, prolaktien- en SSS- bemiddelde effekte waargeneem. Daar is geen risperidoon verwante

teratogeniese effek in enige navorsingstudie bemerk nie.

Pasgeborenes wat blootgestel word aan antipsigotiese medisyne (insluitende RISPERDAL CONSTA)

tydens die derde trimester van swangerskap is aan ’n risiko vir ekstrapiramidale en/of

onttrekkingsimptome na geboorte onderwerp, dit kan wissel in erns. Hierdie simptome in die

pasgeborene kan insluit onrustigheid, hipertonie, hipotonie, bewing, lomerigheid, respiratoriese nood,

of voedingsteurnis.

Gevolglik behoort RISPERDAL CONSTA slegs in swangerskap gebruik te word indien die voordele

voordelig teen die risiko’s opweeg.

Laktasie:

In dierestudies word risperidoon en 9-hidroksierisperidoon in die melk uitgeskei. Dit is aangetoon dat

risperidoon en 9-hidroksierisperidoon ook in menslike borsmelk uitgeskei word. Daarom behoort

vroue wat RISPERDAL CONSTA ontvang, nie hul babas te borsvoed nie.

DOSIS EN GEBRUIKSAANWYSINGS

Daar word aanbeveel dat verdraagbaarheid vir risperidoon eers met orale risperidoon bepaal word

voordat behandeling met RISPERDAL CONSTA begin word by risperidoon-naïewe pasiënte.


CCDS Jan 2013 of 56

Wanneer daar begin word met RISPERDAL CONSTA, moet die pasiënt ’n orale antipsigotiese

medisyne daarmee saam ontvang vir ten minste drie weke, aangesien terapeutiese konsentrasies

van RISPERDAL CONSTA eers na ’n drie weke tydperk bereik word.

RISPERDAL CONSTA moet ten minste elke twee weke deur ’n diep intramuskulêre gluteale

inspuiting toegedien word, deur gebruik te maak van die ingeslote veiligheidsnaald. Vir gluteale

toediening, gebruik die 5,08 cm naald en wissel inspuitings af tussen die twee boude. Moenie

intraveneus toedien nie (sien WAARSKUWINGS en Aanwysings vir Gebruik en Hantering).

Volwassenes

Die aanbevole dosis is 25 mg intramuskulêr elke twee weke. Sommige pasiënte kan baat vind by die

hoër dosisse van 37,5 mg of 50 mg. Geen addisionele voordeel is waargeneem met 75 mg in

kliniese proewe by pasïente met skisofrenie nie. Dosisse bo 50 mg is nie bestudeer by pasïente met

bipolëre versteurings nie.

Dosisse bo 50 mg elke 2 weke word nie aanbeveel nie.

Opwaartse dosisaanpassing moet nie meer dikwels as 4-weekliks geskied nie. Die effek van hierdie

dosisaanpassing moet nie vroër as 3 weke na die eerste inspuiting met die hoër dosis verwag word

nie.

Bejaardes

Die aanbevole dosis is 25 mg intramuskulêr elke twee weke.

Nier- en lewerinkorting

RISPERDAL CONSTA is nie by pasiënte met lewer- en nierinkorting nagevors nie.

NAALD-VRYE FLESSIE TOEGANGSTOESTEL:

RISPERDAL® CONSTA® benodig noukeurige aandag aan die stap-vir-stap

“Gebruiksaanwysings” om suksesvolle toediening te help verseker en om probleme met die

gebruik van die toestel te vermy.

RISPERDAL CONSTA poeier in flessie moet slegs met die verdunningsmiddel in

doseringspakkie hersaamgestel word en moet slegs met die geskikte naald vir gluteale

(5,08 cm naald) , wat in die pakkie voorsien word, toegedien word. Moenie enige van


CCDS Jan 2013 of 56

die komponente in die doseringspakkie met ander vervang nie. Om te verseker dat die

bedoelde dosis van risperidoon gelewer word, moet die volledige inhoud van die flessie

toegedien word. Toediening van slegs ’n deel van die inhoud kan moontlik nie die

bedoelde dosis van risperidoon lewer nie. Dit is raadsaam om die inspuiting

onmiddellik na hersamestelling toe te dien.

Verwyder die doseringspakkie RISPERDAL CONSTA uit die yskas en laat dit toe om

kamertemperatuur te bereik, vir ongeveer 30 minute, voordat dit hersaamgestel word.

1. Trek die gekleurde plastiekdoppie af van die flessie. Moenie die grys rubberprop verwyder nie.

Vee die grys rubberprop af met ’n alkoholdepper en laat dit toe om droog te word.

2. Trek die stolpsakkie oop en verwyder die SmartSite Needle-Free Vial Access-toestel, deur dit te

hou tussen die wit luer-doppie en die romp.

Moenie op enige tydstip die spitspunt van die toegangstoestel aanraak nie.

3. Dit is baie belangrik dat die SmartSite Needle-Free Vial Access - toegangstoestel korrek

op die flessie geplaas word, of die verdunningsmiddel kan lek as dit oorgeplaas word na

die flessie. Plaas die flessie op ’n ferm oppervlakte. Hou die SmartSite Needle-Free Vial

Access – toegangstoestel vertikaal oor die flessie sodat die spitspunt by die middel van die

flessie se rubberprop is.


CCDS Jan 2013 of 56

Met ’n reguit afwaartse drukbeweging, druk die spitspunt van die SmartSite Needle-Free Vial

Access toegangstoestel deur die middel van die flessie se rubberprop totdat die toestel stewig

klamp aan die bokant van die flessie.

Korrek

Verkeerd

4. Hou vas aan die basis van die flessie en vee die spuit-konneksiepunt (blou sirkel) van die

SmartSite Needle-Free Vial Access toegangstoestel met ’n alkoholdepper en laat dit toe om

droog te word voordat die spuit aan die SmartSite Needle-Free Vial Access toegangstoestel

geheg word.


CCDS Jan 2013 of 56

Die vooraf gevulde spuit het ’n wit punt, bestaande uit 2 dele: ’n wit kraag en ’n gladde wit

doppie. Om die spuit oop te maak, hou die spuit aan die wit kraag en knak die gladde wit

doppie af (MOENIE DIE WIT DOPPIE BUIG OF AFSNY NIE). Verwyder die wit doppie saam

met die rubberpuntdoppie daarbinne.

Hou die spuit slegs aan die wit kraag wat geleë is aan die punt van die spuit, tydens alle stappe

in die samestelling van die spuit. Dit sal help om te voorkom dat die wit kraag loskom en

ook ’n goeie konneksie met die spuit verseker, as daar vasgehou word aan die wit kraag.

Wees versigtig om nie komponente te styf te maak as dit saamgestel word nie. Te stywe

konneksies kan veroorsaak dat van die spuit komponente loskom van die spuitromp.

5. Terwyl daar vasgehou word aan die wit kraag van die spuit, druk die spuitpunt in die blou kring

van die SmartSite Needle-Free Vial Access toegangstoestel en draai dit in ’n kloksgewyse

beweging om die konneksie met die spuit aan die SmartSite Needle-Free Vial Access

toegangstoestel te verseker (moenie te styf draai nie).

Hou die romp van die SmartSite Needle-Free Vial Access toegangstoestel vas tydens

vashegting, om draaiing te voorkom.

Hou die spuit en die SmartSite Needle-Free Vial Access Device toegangstoestel in lyn met

mekaar.


CCDS Jan 2013 of 56

6. Spuit die hele inhoud van die spuit, bevattende die verdunningsmiddel, in die flessie in.

7. Skud die flessie KRAGTIG terwyl die plonsstaaf met die duim afgehou word; skud die flessie

ten minste 10 sekondes deeglik om ’n homogene suspensie te verseker.

Wanneer dit behoorlik gemeng is, kom die suspensie voor as eenvormig, dik en melkerig van

kleur. Die mikrosfere sal sigbaar wees in vloeistof maar geen droë mikrosfere bly agter nie.

MOENIE DIE FLESSIE NA HERSAMESTELLING BÊRE NIE, WANT DIE SUSPENSIE KAN

UITSAK.


CCDS Jan 2013 of 56

8. Draai die flessie heeltemal om en trek STADIG die hele inhoud van die suspensie uit die flessie

in die spuit op.

Skeur die etiket af by die perforasie en wend die afgeskeurde etiket aan die spuit vir

identifikasiedoeleindes.

9. Terwyl daar vasgehou word aan die wit kraag van die spuit, skroef die spuit los van die

SmartSite Needle-Free Vial Access Device toegangstoestel. Doen op ’n geskikte wyse weg

met die flessie en die toegangstoestel vir die flessie.

10. Maak die naaldpakkie oop en kies die gepaste naald, wat met die pakkie voorsien word.

MOENIE raak aan die konneksiepunt van die naald nie, raak slegs aan die deurskynende

skede van die naald.

Vir GLUTEALE inspuiting, kies die 20G TW 5,08 cm naald (die langer naald met die

geelkleurige naaf).


CCDS Jan 2013 of 56

11. Om kontaminasie te vermy, wees versigtig om nie te raak aan die oranje Needle-Pro safety

toestel se luer-konneksie nie. Terwyl daar vasgehou word aan die wit kraag van die spuit,

heg die luer-konneksie van die oranje Needle-Pro safety toestel aan die spuit, met ’n

gemaklike kloksgewyse draaibeweging.

12. Terwyl daar steeds vasgehou word aan die wit kraag van die spuit, neem die deurskynende

naaldskag en plaas die naald stewig op die oranje Needle-Pro® safety toestel met ’n druk en

kloksgewyse draai. Vestiging van die naald sal help om te verseker dat daar ’n veilige

konneksie is tussen die naald en die oranje Needle-Pro safety toestel, terwyl die

volgende stappe uitgevoer word.

13. HERSUSPENDERING VAN RISPERDAL CONSTA SAL BENODIG WORD VOOR

TOEDIENING, AANGESIEN UITSAKKING MET VERLOOP VAN TYD SAL VOORKOM


CCDS Jan 2013 of 56

NADAT DIE PRODUK HERSAAMGESTEL IS. HERSUSPENDEER DIE MIKROSFERE IN

DIE SPUIT, DEUR DIT HEWIG TE SKUD.

14. Terwyl daar vasgehou word aan die wit kraag van die spuit, trek die deursigtige naaldskede

reguit af van die naald. MOENIE DIE SKEDE BUIG nie, aangesien die luer-konneksies kan

loskom.

15. Tik die spuit liggies om enige lugborrels na boontoe te dryf.

Verwyder die lug in die spuit deur die plonsstaaf stadig en versigtig in te druk terwyl die naald in

’n regop posisie gehou word. Spuit onmiddellik die hele inhoud van die spuit intramuskulêr in

die verkose gluteale spier van die pasiënt. Gluteale inspuiting moet gedoen word in die

boonste buite-kwadrant van die gluteale streek.

MOENIE INTRAVENEUS TOEDIEN NIE.

WAARSKUWING: Om ’n naaldsteek-besering met ’n gekontamineerde naald te vermy -

Moenie die vry hand gebruik om die Needle-Pro veiligheidstoestel oor die naald te druk

nie.


CCDS Jan 2013 of 56

Moenie doelbewus die Needle-Pro veiligheidstoestel losmaak nie.

Moenie probeer om die naald reguit te maak of die Needle-Pro toestel te gebruik as die

naald gebuig of beskadig is nie.

Moenie die Needle-Pro veiligheidstoestel verkeerd hanteer nie, aangesien dit kan

veroorsaak dat die naald uit die Needle-Pro veiligheidstoestel kan druk.

16. Nadat die inspuiting afgehandel is, druk die naald in die oranje Needle-Pro® veiligheidstoestel

met behulp van ’n een-hand tegniek. Voer die een-hand tegniek uit deur die oranje Needle-

Pro® veiligheidstoestel LIGGIES op ’n plat oppervlakte te druk. SOOS DIE ORANJE

NEEDLE-PRO® VEILIGHEIDSTOESTEL GEDRUK WORD, SAL DIE NAALD STEWIG

GEVESTIG WORD IN DIE ORANJE NEEDLE-PRO® VEILIGHEIDSTOESTEL. Bevestig deur

te kyk of die naald ten volle in die oranje Needle-Pro® veiligheidstoestel gevestig is voordat dit

weggegooi word. Doen op geskikte wyse weg met die naald. Doen ook weg met die ander

(ongebruikte) naald, wat in die doseringspakkie voorsien word.

Moenie hergebruik nie: Mediese toestelle benodig materiale met spesifieke eienskappe om volgens

die bedoelde wyse gebruik te word. Hierdie eienskappe is slegs vir enkele gebruik nagevors. Enige

poging om die toestel te hergebruik kan die integriteit van die toestel nadelig beïnvloed, of die

werking daarvan belemmer.

NEWE-EFFEKTE

Kliniese proewe data

Die mees dikwels aangemelde ongunstige geneesmiddelreaksies (OGR’s) (insidensie 1/10) is:

Slaaploosheid, angs, hoofpyn, boonste lugweginfeksie, Parkinsonisme, depressie en akatisie.


CCDS Jan 2013 of 56

Die volgende sluit al die OGR’s in wat met kliniese proewe aangemeld is. Die volgende terminologie

en frekwensies is toegepas: baie algemeen (≥ 1/10), algemeen (≥ 1/100 tot <1/10), ongewoon

(≥ 1/1 000 tot <1/100), seldsaam (≥ 1/10 000 tot <1/1 000), baie seldsaam (< 1/10 000), en onbekend

(kan nie geskat word uit die beskikbare kliniese proewe se data nie).

Binne elke frekwensiegroepering word ongewenste effekte in volgorde van afnemende erns

weergegee.

Ongunstige geneesmiddelreaksies volgens orgaansisteemklas en frekwensie:

Ondersoeke

Algemeen Elektrokardiogram abnormaal, bloed-prolaktiena

verhoog, bloed-glukose verhoog, lewerensieme

verhoog, transaminase verhoog, gamma-

glutamieltransferase verhoog, gewigstoename,

gewig verminder.

Ongewoon Elektrokardiogram QT-verlenging.

Hartsiektes

Algemeen Atrioventrikulêre blok, tagikardie.

Ongewoon Takbondelblok, bradikardie, sinus bradikardie,

palpitasies.

Bloed- limfstelselsiektes

Algemeen Anemie.

Ongewoon Neutropenie.

Senuweestelsel siektes

Baie algemeen Parkinsonismeb, akatisieb, hoofpyn.

Algemeen duiseligheid, sedasie, lomerigheid, tremor,

distonieb, tardiewe diskinesie, diskineseb.

Ongewoon Konvulsie, sinkopee, posturale duiseligheid,

hipestesie, parestesie, letargie, hipersomnie.

Oogsiektes

Algemeen Dowwe visie, konjunktivitis.

Oor- en doolhofsiektes

Algemeen

Ongewoon

Vertigo.

Oorpyn.

Respiratoriese, bors- en mediastinumsiektes


CCDS Jan 2013 of 56

Algemeen Dispnee, hoes, neuskongestie, faringo-

laringeale pyn.

Gastroïntestinale siektes

Algemeen Braking, diarree, konstipasie, naarheid, buikpyn,

dispepsie, tandpyn, droë mond, maag-ongemak,

gastritis.

Nier- en urienwegsiektes

Algemeen

Ongewoon

Urinêre inkontinensie.

Urinêre retensie.

Vel- en onderhuidse weefselsiektes

Algemeen Uitslag, ekseem.

Ongewoon Pruritus, aknee, droë vel.

Skeletspier- en bindweefsel siektes

Algemeen Artralgie, rugpyn, pyn in ledemate, mialgie.

Ongewoon Spierswakheid, nekpyn, boudpyn, skeletspier-

borspyn.

Metabolisme en voedingsiektes

Algemeen Hiperglisemie.

Ongewoon Verhoogde aptyt, verminderde aptyt.

Infeksies en infestasies

Baie algemeen Boonste lugweginfeksie.

Algemeen Pneumonie, influensa, onderste lugweginfeksie,

brongitis, urienweg infeksie, oorinfeksie,

sinusitis, virus infeksie, rinitis, faringitis.

Ongewoon Sistitis, gastroënteritis, infeksie, plaaslike

infeksie, subkutane abses.

Besering, vergiftiging en prosedure-komplikasies

Algemeen Val.

Ongewoon Pyn van prosedure.

Vaskulêre siektes

Algemeen Hipertensie, hipotensie.

Ongewoon Ortostatiese hipotensie.

Algemene siektes en toestande by die plek van toediening

Algemeen Pireksie, perifere edeem, borspyn, moegheid, pyn

by inspuitingsplek, astenie, griepagtige

ongesteldheid, onwel gevoel.


CCDS Jan 2013 of 56

Ongewoon Verharding by plek van inspuiting, verharding,

bors ongemak, traagheid, abnormale gevoel.

Immuunstelsel siektes

Ongewoon Hipersensitiwiteit.

Voortplantingstelsel en bors siektes

Algemeen Amenorree, ereksie disfunksie, galaktoree,

oligomenorree, bors ongemak, ejakulasie

versteuring.

Ongewoon Seksuele disfunksie, ginekomastie.

Psigiatriese siektes

Baie algemeen Depressie, slaaploosheid, angs.

Algemeen Agitasie, slaapsiekte.

Ongewoon Libido verminder, senuweeagtigheid.

a) Hiperprolaktienemie kan by sommige gevalle lei tot ginekomastie, menstruele versteurings,

amenorree, galaktoree.

b) Ekstrapiramidale afwykings kan voorkom: Parkinsonisme (speeksel hipersekresie,

skeletspierstyfheid, Parkinsonisme, kwyl, tandrat-styfheid, bradikinesie, hipokinese, maskergesig,

spierstyfheid, akinesie, nekstyfheid, spierstyfheid, Parkinson-stap, en glabella- refleks abnormaal),

akatisie (akatisie, rusteloosheid, hiperkinesie en rustelose been sindroom), tremor, diskinesie

(diskinesie, spiertrekkings, choreoatetose, atetose en mioklonus), distonie. Distonie sluit in distonie,

spierspasma, hipertonie, tortikollis, onwillekeurige spierkontraksies, spierkontraksies, blefarospasma,

oogtolling, tong-paralise, gesig-spasma, laringospasma, miotonie, opistotonus, orofaringeale spasma,

pleurototonus, tong-spasma en trismus. Tremor sluit in tremor en Parkinson-rustremor. Let daarop

dat ’n wyer spektrum van simptome ingesluit is, wat nie noodwendig ’n ekstrapiramidale oorsprong

het nie.

Na-bemarkingsdata

Newe-effekte wat eers met ervaring na bemarking met RISPERDAL CONSTA waargeneem is.

Bloed- en limfstelsel siektes

Agranulositose, trombositopenie.

Endokriene siektes

Ontoepaslike antidiuretiese hormoonafskeiding.


CCDS Jan 2013 of 56

Metabolisme en voedingsiektes

Diabetiese ketoasidose, diabetes mellitus, hipoglukemie, water intoksikasie, bloed- cholesterol verhoog,

bloed-trigliseriede verhoog.

Psigiatriese siektes

Manie.

Senuweestelsel siekte

Disgeusie.

Oog siektes

Retina-aar verstoppinga.

Slap-iris-sindroom (intra-operatief).

Hart siektes

Atriale fibrillasie.

Vaatsiektes

Diep-veneuse trombose, pulmonale embolisme.

Respiratoriese-, bors- en mediastinum siektes

Slaap apnee sindroom.

Gastroïntestinale siektes

Pankreatitis,

Dermverlamming.

Hepatobiliêre siektes

Geelsug.

Vel- en onderhuidse weefsel siektes

Angioëdeem, alopesie.

Nier-en urienwegsiektes


CCDS Jan 2013 of 56

Urien retensie.

Swangerskap, peurperium en perinatale toestande

Neonatale geneesmiddel-onttrekking sindroom.

Voortplantingstelsel en bors siektes

Priapisme.

Algemene siektes

Hipotermie, reaksie by plek van inspuiting, insluitende abses by plek van inspuiting, sellulitis, sist,

hematoom, nekrose, nodule en sweer.

a Slegs RISPERDAL CONSTA formulering, aangemeld in die teenwoordigheid van ’n intrakardiale

defek wat predisponeer tot ’n regs-tot-links omleiding (bv. ’n duidelike foramen ovale).

Hipersensitiwiteit

Gevalle van 'n anafilaktiese reaksie na inspuiting van RISPERDAL CONSTA by pasiënte wat

voorheen mondelike risperidoon verdra het, is tydens nabemarkingservaring aangemeld.

BEKENDE SIMPTOME VAN OORDOSERING EN BESONDERHEDE VAN DIE BEHANDELING

DAARVAN

Simptome:

Aangemelde tekens en simptome was dié wat voorgekom het as gevolg van verergering van die

middel se bekende farmakologiese werking. Simptome van akute oordosering sluit lomerigheid,

sedering, hipotensie, tagikardie en ekstrapiramidale simptome in. Gevalle van QT-verlenging en

konvulsies is met oordosering aangemeld. Torsades de pointes is aangemeld in assosiasie met

gekombineerde oordosering van orale RISPERDAL en paroksetien. In die geval van akute

oordosering behoort die moontlikheid van betrokkenheid van veelvuldige medisynes oorweeg te

word.

Behandeling:


CCDS Jan 2013 of 56

Verkry en behou ’n oop lugweg en verseker voldoende suurstof toevoer en ventilering.

Kardiovaskulêre monitering moet onmiddellik begin word en behoort deurlopende

elektrokardiografiese monitering in te sluit om moontlike disritmie waar te neem.

Aangesien daar geen bekende teenmiddel bestaan indien toevallige vergiftiging vermoed word nie,

behoort toepaslike ondersteunende maatreëls getref te word. Hipotensie en sirkulatoriese

ineenstorting behoort met toepaslike maatreëls soos intraveneuse vloeistowwe en/of

simpatomimetiese middels behandel te word. In die geval van erge ekstrapiramidale simptome,

behoort anticholinergiese medikasie toegedien te word. Noukeurige mediese toesig en monitering

behoort voortgesit te word totdat die pasiënt herstel.

IDENTIFIKASIE

Helder, kleurlose, glasflessie met ’n grys rubberprop, styf geklamp, gekleurde afwip-deksel* met ’n

wit, vry vloeiende poeier, vry van sigbare vreemde materiaal, suspendeer geredelik sonder

klontvorming of sigbare vreemde materiaal.

* Die kleur van die afwip-deksel word geverifieer – die kleur wissel volgens dosissterkte, soos volg:

Pienk : 25 mg risperidoon per flessie

Groen: 37,5 mg risperidoon per flessie

Blou: 50 mg risperidoon per flessie

Voorafgevulde spuit met verdunningsmiddel vir hersamestelling:

Helder, kleurlose, waterige oplossing sonder sigbare vreemde materiale.

AANBIEDING

Naaldvrye flessie toegangstel:

- Een 5 ml flessie bevattende RISPERDAL CONSTA poeier vir suspensie vir inspuiting.

- Een AlarisTM SmartSite® “Needle-free Vial Access” toegangstoestel vir hersamestelling.

- Een 3 ml voorafgevulde spuit bevattende 2 ml verdunningsmiddel vir RISPERDAL CONSTA.

- Een naald vir intramuskulêre inspuiting (’n 20G TW 5,08 cm veiligheidsnaald met die Needle-Pro

veiligheidstoestel vir gluteale toediening). (“Rx- only”- dit is ’n toestel wat slegs met voorskrifmedisyne

verskaf word).


CCDS Jan 2013 of 56

BERGINGSINSTRUKSIES

Die hele doseringspakket moet in die yskas bewaar word (2 - 8 °C.) en beskerm word teen lig. Dit

moet nie aan temperature bo 25 °C., blootgestel word nie.

Indien verkoeling nie beskikbaar is nie, kan RISPERDAL CONSTA bewaar word by temperature wat

nie 25 °C., oorskry nie, vir nie meer as 7 dae voor toediening nie. Moenie onverkoelde produk aan

temperature bo 25 °C., blootstel nie.

HOU BUITE BEREIK VAN KINDERS.

REGISTRASIENOMMERS

Risperdal CONSTA 25, 37,5 & 50 mg: 37/2.6.5/0142 - 4

NAAM EN BESIGHEIDSADRES VAN DIE APPLIKANT

JANSSEN PHARMACEUTICA (PTY) LTD


CCDS Jan 2013 of 56

(Reg. No.: 1980/011122/07)

Building 6, Country Club Estate, 21 Woodlands Drive, Woodmead, 2191

Tel: +27 (11) 518 7000

www.janssen.co.za

DATUM VAN PUBLIKASIE VAN HIERDIE VOUBILJET

28 November 2014

http://www.janssen.co.za/

FINAL AMENDED PACKAGE INSERT

Documents

Transcript of FINAL AMENDED PACKAGE INSERT