Posology : מינונים

2 DOSAGE AND ADMINISTRATION
For patients who have never taken oral RISPERDAL®, it is recommended to establish tolerability with oral RISPERDAL® prior to initiating treatment with RISPERDAL CONSTA®.


RISPERDAL CONSTA® should be administered every 2 weeks by deep intramuscular (IM) deltoid or gluteal injection. Each injection should be administered by a health care professional using the appropriate enclosed safety needle [see Dosage and Administration (2.8)]. For deltoid administration, use the 1-inch needle alternating injections between the two arms. For gluteal administration, use the 2-inch needle alternating injections between the two buttocks. Do not administer intravenously.

2.1    Schizophrenia
The recommended dose for the treatment of schizophrenia is 25 mg IM every 2 weeks. Although dose response for effectiveness has not been established for RISPERDAL CONSTA®, some patients not responding to 25 mg may benefit from a higher dose of 37.5 mg or 50 mg. The maximum dose should not exceed 50 mg RISPERDAL CONSTA® every 2 weeks. No additional benefit was observed with dosages greater than 50 mg RISPERDAL CONSTA®; however, a higher incidence of adverse effects was observed.


The efficacy of RISPERDAL CONSTA® in the treatment of schizophrenia has not been evaluated in controlled clinical trials for longer than 12 weeks. Although controlled studies have not been conducted to answer the question of how long patients with schizophrenia should be treated with RISPERDAL CONSTA®, oral risperidone has been shown to be effective in delaying time to relapse in longer term use. It is recommended that responding patients be continued on treatment with RISPERDAL CONSTA® at the lowest dose needed. The physician who elects to use RISPERDAL CONSTA® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.


2.2   Bipolar Disorder
The recommended dose for monotherapy or adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder is 25 mg IM every 2 weeks. Some patients may benefit from a higher dose of 37.5 mg or 50 mg. Dosages above 50 mg have not been studied in this population. The physician who elects to use RISPERDAL CONSTA® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.3   General Dosing Information
A lower initial dose of 12.5 mg may be appropriate when clinical factors warrant dose adjustment, such as in patients with hepatic or renal impairment, for certain drug interactions that increase risperidone plasma concentrations [see DRUG INTERACTIONS (7.11)] or in patients who have a history of poor tolerability to psychotropic medications. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Oral RISPERDAL® (or another antipsychotic medication) should be given with the first injection of RISPERDAL CONSTA® and continued for 3 weeks (and then discontinued) to ensure that adequate therapeutic plasma concentrations are maintained prior to the main release phase of risperidone from the injection site [see Clinical Pharmacology (12.3)].


Upward dose adjustment should not be made more frequently than every 4 weeks. The clinical effects of this dose adjustment should not be anticipated earlier than 3 weeks after the first injection with the higher dose.


In patients with clinical factors such as hepatic or renal impairment or certain drug interactions that increase risperidone plasma concentrations [see DRUG INTERACTIONS (7.11)], dose reduction as low as 12.5 mg may be appropriate. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Do not combine two different dose strengths of RISPERDAL CONSTA® in a single administration.

2.4    Dosage in Special Populations
Elderly
For elderly patients treated with RISPERDAL CONSTA®, the recommended dosage is 25 mg IM every 2 weeks. Oral RISPERDAL® (or another antipsychotic medication) should be given with the first injection of RISPERDAL CONSTA® and should be continued for 3 weeks to ensure that adequate therapeutic plasma concentrations are maintained prior to the main release phase of risperidone from the injection site [see Clinical Pharmacology (12.3)].


Renal or Hepatic Impairment
Patients with renal or hepatic impairment should be treated with titrated doses of oral RISPERDAL® prior to initiating treatment with RISPERDAL CONSTA®. The recommended starting dose is 0.5 mg oral RISPERDAL® twice daily during the first week, which can be increased to 1 mg twice daily or 2 mg once daily during the second week. If a total daily dose of at least 2 mg oral RISPERDAL® is well tolerated, an injection of 25 mg RISPERDAL CONSTA® can be administered every 2 weeks. Oral supplementation should be continued for 3 weeks after the first injection until the main release of risperidone from the injection site has begun. In some patients, slower titration may be medically appropriate. Alternatively, a starting dose of RISPERDAL CONSTA® of 12.5 mg may be appropriate. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.


Patients with renal impairment may have less ability to eliminate risperidone than normal adults.
Patients with impaired hepatic function may have an increase in the free fraction of the risperidone, possibly resulting in an enhanced effect [see Clinical Pharmacology (12.3)]. Elderly patients and patients with a predisposition to hypotensive reactions or for whom such reactions would pose a particular risk should be instructed in nonpharmacologic interventions that help to reduce the occurrence of orthostatic hypotension (e.g., sitting on the edge of the bed for several minutes before attempting to stand in the morning and slowly rising from a seated position). These patients should avoid sodium depletion or dehydration, and circumstances that accentuate hypotension (alcohol 
intake, high ambient temperature, etc.). Monitoring of orthostatic vital signs should be considered [see Warnings and Precautions (5.7)].

2.5    Reinitiation of Treatment in Patients Previously Discontinued
There are no data to specifically address reinitiation of treatment. When restarting patients who have had an interval off treatment with RISPERDAL CONSTA®, supplementation with oral RISPERDAL® (or another antipsychotic medication) should be administered.

2.6    Switching from Other Antipsychotics
There are no systematically collected data to specifically address switching patients from other antipsychotics to RISPERDAL CONSTA®, or concerning concomitant administration with other antipsychotics. Previous antipsychotics should be continued for 3 weeks after the first injection of RISPERDAL CONSTA® to ensure that therapeutic concentrations are maintained until the main release phase of risperidone from the injection site has begun [see Clinical Pharmacology (12.3)]. For patients who have never taken oral RISPERDAL®, it is recommended to establish tolerability with oral RISPERDAL® prior to initiating treatment with RISPERDAL CONSTA®.
As recommended with other antipsychotic medications, the need for continuing existing EPS medication should be re evaluated periodically.

2.7 Co-Administration of RISPERDAL® CONSTA® with Certain Other
Medications

Co-administration of carbamazepine and other CYP 3A4 enzyme inducers (e.g., phenytoin, rifampin, phenobarbital) with risperidone would be expected to cause decreases in the plasma concentrations of the sum of risperidone and 9-hydroxyrisperidone combined, which could lead to decreased efficacy of RISPERDAL CONSTA® treatment. The dose of risperidone needs to be titrated accordingly for patients receiving these enzyme inducers, especially during initiation or discontinuation of therapy with these inducers [see Drug Interactions (7.11)]. At the initiation of therapy with carbamazepine or other known CYP 3A4 hepatic enzyme inducers, patients should be closely monitored during the first 4-8 weeks, since the dose of RISPERDAL CONSTA® may need to be adjusted. A dose increase, or additional oral RISPERDAL®, may need to be considered.
On discontinuation of carbamazepine or other CYP 3A4 hepatic enzyme inducers, the dosage of RISPERDAL CONSTA® should be re-evaluated and, if necessary, decreased. Patients may be placed on a lower dose of RISPERDAL CONSTA® between 2 to 4 weeks before the planned discontinuation of carbamazepine or other CYP 3A4 inducers to adjust for the expected increase in plasma concentrations of risperidone plus 9- hydroxyrisperidone. For patients treated with the recommended dose of 25 mg RISPERDAL CONSTA® and discontinuing from carbamazepine or other CYP3A4 enzyme inducers, it is recommended to continue treatment with the 25-mg dose 
unless clinical judgment necessitates lowering the RISPERDAL CONSTA® dose to 12.5 mg or necessitates interruption of RISPERDAL CONSTA® treatment. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.


Fluoxetine and paroxetine, CYP 2D6 inhibitors, have been shown to increase the plasma concentration of risperidone 2.5-2.8 fold and 3-9 fold respectively. Fluoxetine did not affect the plasma concentration of 9- hydroxyrisperidone. Paroxetine lowered the concentration of 9- hydroxyrisperidone by about 10%. The dose of risperidone needs to be titrated accordingly when fluoxetine or paroxetine is co-administered. When either concomitant fluoxetine or paroxetine is initiated or discontinued, the physician should re-evaluate the dose of RISPERDAL CONSTA®.
When initiation of fluoxetine or paroxetine is considered, patients may be placed on a lower dose of RISPERDAL CONSTA® between 2 to 4 weeks before the planned start of fluoxetine or paroxetine therapy to adjust for the expected increase in plasma concentrations of risperidone.
When fluoxetine or paroxetine is initiated in patients receiving the recommended dose of 25 mg RISPERDAL CONSTA®, it is recommended to continue treatment with the 25 mg dose unless clinical judgment necessitates lowering the RISPERDAL CONSTA® dose to 12.5 mg or necessitates interruption of RISPERDAL CONSTA® treatment. When RISPERDAL CONSTA® is initiated in patients already receiving fluoxetine or paroxetine, a starting dose of 12.5 mg can be considered. The efficacy of the 12.5 mg dose has not been investigated in clinical trials. The effects of discontinuation of concomitant fluoxetine or paroxetine therapy on the pharmacokinetics of risperidone and 9-hydroxyrisperidone have not been studied. [see Drug Interactions (7.11)]

2.8    Instructions for Use
For deltoid or gluteal intramuscular injection only

Important Information
RISPERDAL CONSTA® requires close attention to these step-by-step ‘Instructions for Use to help ensure successful administration.
Use components provided
The components in this dose pack are specifically designed for use with RISPERDAL CONSTA®. RISPERDAL CONSTA® must be reconstituted only in the diluent supplied in the dose pack.
Do not substitute ANY components of the dose pack.
Do not store suspension after reconstitution
Administer dose as soon as possible after reconstitution to avoid settling.

Proper dosing
The entire contents of the vial must be administered to ensure intended dose of RISPERDAL CONSTA® is delivered.


SINGLE-USE DEVICE

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.

Dose pack contents



Step 1           Assemble components
Take out dose pack            Connect vial adapter to vial



Wait 30 minutes         Remove cap from        Prepare vial            Connect vial adapter Remove dose pack        vial                   adapter                 to vial from the refrigerator   Flip off colored cap   Hold sterile blister    Place vial on a hard and allow to sit at     from vial.             as shown. Peel back     surface and hold by the room temperature                               and remove paper        base. Center vial adapter for at least 30         Wipe top of the grey   backing.                over the grey rubber minutes before          stopper with an                                stopper. Push vial reconstituting.         alcohol swab. Allow    Do not remove vial      adapter straight down to air dry.            adapter from blister.   onto vial top until it Do not warm any                                                        snaps securely into other way.              Do not remove grey     Do not touch spike      place.
rubber stopper.        tip at any time. This will result in          Do not place vial contamination.          adapter on at an angle or diluent may leak upon transfer to the vial.



Connect prefilled syringe to vial adapter



Remove sterile           Use proper grip            Remove cap                 Connect syringe to blister                  Hold by white collar       Holding the white          vial adapter at the tip of the          collar, snap off the       Hold vial adapter by syringe.                   white cap.                 skirt to keep stationary.
Do not hold syringe        Do not twist or cut by the glass barrel        off the white cap.         Hold syringe by during assembly.                                      white collar then Do not touch syringe insert tip into the luer tip. This will result in
Keep vial vertical to                                                          opening of the vial contamination.
prevent leakage.                                                               adapter.
Hold base of vial and
Do not hold the glass pull up on the sterile syringe barrel. This blister to remove.
may cause the white collar to loosen or
Do not shake.
detach.
The broken-off cap
Do not touch                                        can be discarded.          Attach the syringe to exposed luer opening                                                           the vial adapter with on vial adapter.                                                               a firm clockwise This will result in                                                            twisting motion until contamination.                                                                 it feels snug.
Do not over-tighten.
Over-tightening may cause the syringe tip to break.



Step 2           Reconstitute microspheres



Inject diluent           Suspend                       Transfer suspension    Remove vial Inject entire amount                                   to syringe             adapter microspheres in of diluent from diluent                       Invert vial            Hold white collar on syringe into the vial.
Continuing to hold            completely. Slowly     the syringe and down the plunger rod,         pull plunger rod       unscrew from vial shake vigorously for          down to withdraw       adapter.
at least 10 seconds, as       entire contents from the vial into the      Tear section of the shown.                                               vial label at the syringe.
Check the suspension.                                perforation. Apply When properly mixed,                                 detached label to the the suspension appears                               syringe for uniform, thick and                                   identification milky in color.                                      purposes.
Microspheres will be                                 Discard both vial visible in the liquid.                               and vial adapter Immediately proceed                                  appropriately.
to the next step so suspension does not settle.



Step 3         Attach needle



Select appropriate needle   Attach needle                    Resuspend microspheres Choose needle based on      Peel blister pouch open part     Fully remove the blister injection location          way and use to grasp the base    pouch.
(gluteal or deltoid).       of the needle, as shown.         Just before injection, shake Holding the white collar on      syringe vigorously again, as the syringe, attach syringe to   some settling will have needle luer connection with a    occurred.
firm clockwise twisting motion until snug.
Do not touch needle luer opening. This will result in contamination.



Step 4         Inject dose



Remove               Remove air         Inject               Secure needle in        Properly dispose transparent          bubbles            Immediately inject   safety device           of needles needle protector     Hold needle        entire contents of   Using one hand,         Check to confirm Move the needle      upright and tap    syringe              place needle safety     needle safety safety device back   gently to make     intramuscularly      device at a 45-         device is fully towards the          any air bubbles    (IM) into the        degree angle on a       engaged.
syringe,             rise to the top.   gluteal or deltoid   hard, flat surface.     Discard in an as shown. Then       Slowly and         muscle of the        Press down with a       approved sharps hold white collar    carefully press    patient.             firm, quick motion      container.
on syringe and       plunger rod                             until needle is fully Gluteal injection                            Also discard the carefully pull the   upward to remove                        engaged in safety should be made                               unused needle transparent needle   air.                                    device.
into the upper-                              provided in the protector straight outer quadrant of                            dose pack.
off.
the gluteal area.    Avoid needle stick
Do not twist                                                 injury: transparent needle                      Do not administer protector, as the                       intravenously.    Do not use two luer connection                                           hands.
may loosen.                                                  Do not intentionally disengage or mishandle the needle safety device.
Do not attempt to straighten the needle or engage the safety device if the needle is bent or damaged.