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Paliperidone Long Acting Injection (Xeplion®) Guidance for Prescribing and Administration

Main points 1. Long Acting Injection (Paliperidone LAI) is indicated for maintenance treatment of in adult patients stabilised with paliperidone or (Note – oral paliperidone is a non-formulary drug in the AWP Trust formulary). In selected adult patients with schizophrenia and previous responsiveness to oral risperidone (or paliperidone), paliperidone LAI may be used without prior stabilisation with oral treatment if psychotic symptoms are mild to moderate and a long-acting injectable treatment is needed.

2. Paliperidone LAI is not indicated for treatment-resistant schizophrenia, unlicensed indications (e.g. , bipolar, personality disorder) or patients intolerant to oral risperidone or paliperidone.

3. Paliperidone LAI may ONLY be newly prescribed by consultant psychiatrists. Other grades may initiate, but ONLY with direct instruction from their consultant.

4. Risperidone LAI should no longer be initiated for new patients. For those patients who have shown a response to oral risperidone (or paliperidone) with no ADRs and where a LAI is required, paliperidone LAI should be considered in the first instance.

5. Those patients who are stable on risperidone LAI, should remain on RLAI unless there is a need to switch.

6. Paliperidone LAI is intended for once-monthly injection (i.e. once per calendar month, not 4-weekly), by intramuscular (IM) injection into the deltoid or gluteal muscle. However, the loading doses must be given into the deltoid muscle. (See below).

7. Switching from an oral : Paliperidone LAI initiated with 150 mg on day 1 and 100 mg on day 8.in the deltoid muscle to attain therapeutic concentrations rapidly. Oral supplementation should not be required. Following the second dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle. Target maintenance dose is 75mg per month.

8. Switching from risperidone or long acting injection or traditional depot: No loading dose is needed or oral supplementation. Paliperidone LAI should be initiated in place of the next scheduled injection. Paliperidone LAI should then be continued at monthly intervals.

9. Paliperidone LAI is very expensive when compared to traditional antipsychotic depots and is also more expensive than risperidone LAI in terms of procurement costs. PLAI is more costly than LAI. At 100mg per month (equivalent to risperidone consta 50mg per fortnight), it costs ~ £3.800 per patient per year. For cost comparisons, see Appendix 1.

10. Practical comparisons with aripiprazole and risperidone LAI are given in Appendix 2.

11. For ‘Place in therapy’, please see next section.

Prescribing guidelines Paliperidone LAI May 2014 V1.0 BLS Final

Place in therapy

The following criteria should be fulfilled BEFORE Paliperidone LAI is prescribed:

a) Documented ICD – 10 diagnosis for *schizophrenia. b) Dosing schedule will be followed as per SPC c) Service user has been on oral risperidone or risperidone consta with proven response and tolerability. d) Been on 2 or fewer i.e. not treatment resistant when service user should be on .

*if used for unlicensed indication, the ‘Procedure for unlicensed /off label medicines’ must be followed.

Switching from an antipsychotics other than oral risperidone or risperidone LAI to paliperidone LAI should only occur if:

a) current treatment is ineffective b) adverse side-effect profile caused by current treatment excluding metabolic disturbance/ weight gain / cardiac effects / raised prolactin. If these apply, consider Aripiprazole LAI. c) there are adherence issues with current treatment (so monthly injections preferred). d) the service user prefers LAI to oral (i.e. convenience) e) the service user prefers deltoid administration (& RLAI less preferred) f) Where higher doses are needed (150mg) & staying within licensed (75mg RLAI is unlicensed) g) Some patient groups e.g. community patients, where missed dosing is less of an issue as PLAI allows more flexible dosing (unlike RLAI).

Service users stabilised on Risperidone Consta (or other LAI / depot antipsychotic) should NOT be switched as this will carry a risk of destabilisation and hence relapse.

When paliperidone LAI is prescribed for outpatients, it may be obtained from polar speed which is VAT exempt and will save the Trust money. Please ask your locality pharmacist if you require support setting this up.

To avoid a missed dose, service users may be given the second dose 4 days before or after the one-week (day 8) time point. Similarly, the third and subsequent injections after the initiation regimen are recommended to be given monthly. To avoid a missed monthly dose, patients may be given the injection up to 7 days before or after the monthly time point.

Prescribing regimes

Switching form oral antipsychotics:

Patients should be stabilised on oral risperidone (or oral paliperidone), or have shown previous responsiveness to one of them. If not, it is recommended they be stabilised on oral risperidone prior to initiating treatment with paliperidone LAI. (Note: Oral paliperidone is non- formulary and is not in the Trust formulary). Switch from oral risperidone (or oral paliperidone) to paliperidone LAI by replacing the oral drug with an initiation dose of LAI on day 1. This should be followed with a second initiation dose on day 8 as described below. Day 1 - 150mg into the deltoid muscle. Day 8 (+/- 4 days) - 100mg into the deltoid muscle. Prescribing guidelines Paliperidone LAI May 2014 V1.0 BLS Final Day 36 (+/- 7 days) - Maintenance dose into deltoid or gluteal muscle

Switching from risperidone LAI:

Administer the equivalent dose of paliperidone LAI at the time the next scheduled risperidone LAI is due:

Current dose of RLAI: Switch to: Risperidone LAI dose Paliperidone LAI dose 25mg every 2 weeks 50mg monthly 37.5mg every 2 weeks 75mg monthly 50mg every 2 weeks 100mg monthly

Frequency changes from two-weekly to once per calendar month.

Switching from traditional depot injections (There is no specific SPC guidance for this, but advice is taken from information from company).

Administer the paliperidone LAI dose at the time the next scheduled traditional depot injection is due. However, note that it is not possible to accurately determine 'dose equivalents' between paliperidone and traditional depot injections, therefore the choice of dose should be based on clinical experience and individual patient assessment. It is suggested that the dose does not initially exceed 75mg, and that the patient is very closely monitored, both for response and for adverse effects.

The recommended maintenance dose is 75mg per month although some patients may benefit from lower or higher doses, within the range 50mg to 100mg, based on and tolerability.

A maximum maintenance dose of 150mg per month is also available and within the terms of the Product Licence. This dose is equivalent to 75mg risperidone Consta® 2-weekly and should only be prescribed when absolutely necessary as is very costly.

Other Dosing Recommendations / Considerations:

a) The elderly: Efficacy and safety in patients over 65 years of age have not been established. If used, lower doses should be considered particularly if renal function is diminished. The product has not been studied in elderly patients with dementia and should not be used.

b) Children & Adolescents: The product is not licensed for use in patients less than 18 c) years of age. No efficacy or safety data are available.

d) Renal impairment: Lower loading and maintenance doses should be used. Manufacturer’s data should be referred to before prescribing or ask your Locality Pharmacist for advice.

e) Hepatic impairment: No dosage adjustment is required in mild or moderate impairment. Use in severe impairment should be avoided.

Prescribing guidelines Paliperidone LAI May 2014 V1.0 BLS Final Administration

Paliperidone LAI is licensed as a once monthly injection i.e. maintenance dose to be administered 12 times a year – one per calendar month NOT 4-weekly administration as this means the service user will receive maintenance dose 13 times a year, which will NOT provide any greater efficacy but will greatly increase costs.

Following administration of paliperidone LAI there is no requirement for any enhanced level of patient monitoring. Patients should be monitored for post-injection events in the same way as for risperidone LAI or for traditional depot injections.

Storage

Paliperidone LAI should be stored in a locked medicines cabinet; there is no requirement for fridge storage.

Paliperidone LAI is supplied in pre-filled syringes; there is no need for any reconstitution or dilution. Only full syringe doses may be used as the dose administered from less than a full syringe cannot be assured.

Prescribing guidelines Paliperidone LAI May 2014 V1.0 BLS Final

Appendix 1: Cost comparison of Long-Acting Injections (LAI) and depots (Drug Tariff March 2014)

Name Dose Cost per unit Cost per year Paliperidone LAI 50mg monthly £ 183.92 x 12 £ 2207.04 75mg monthly £ 244.90 x 12 £ 2938.80 100mg monthly £ 314.07 x 12 £ 3768.84 150mg monthly £ 392.59 x 12 £ 4711.08 Risperidone LAI 25mg 2- weekly £ 79.69 x 26 £ 2071.94 37.5mg 2-weekly £111.32 x 26 £ 2894.32 50mg 2-weekly £142.76 x 26 £ 3711.76 Olanzapine LAI 150mg 2- weekly £ 142.76 x 26 3711.76 300mg 4-weekly £ 222.64 x13 2894.32 210mg 2-weekly £ 142.76 x 26 3711.76 405mg 4-weekly £ 285.52 x 13 3711.76 300mg 2 weekly £ 222.64 x 26 5788.64 Aripiprazole LAI 400mg monthly £ 220.41 x 12 £ 2644.92 Traditional depot antipsychotics: 200mg every 2 weeks £19.52 x 26 £ 507.52 (200mg/mL) 100mg every 2 weeks £8.79 x 26 £ 228.54 (100mg/mL) 200mg every 4 weeks £10.10 x 13 £ 131.30 (100mg/mL x 2) 200mg every 4 weeks £53.30 x 13 £ 692.90 (50mg/mL.2x2mL amp) 500mg every 2 weeks £7.44 x 26 £ 193.44 (500mg/mL)

**a loading dose for PLAI may not always be necessary if switching from RLAI or depot.

Please note that the costs are not equivocal due to varying loading dosages and varying oral supplementation schedules.

Prescribing guidelines Paliperidone LAI May 2014 V1.0 BLS Final Appendix 2: Practical comparisons of Aripiprazole LAI with Risperidone and Paliperidone LAI.

Paliperidone Long Acting Risperidone Long Acting Aripiprazole Long Injection (PLAI) Injection (RLAI) Acting Injection (ALAI)

Presentation Pre-filled syringe: no Vial & solvent for Vial & solvent for reconstitution needed; may also reconstitution requiring more reconstitution help reduce by service nurse time. requiring more nurse user. time.

Storage None fridge line Requires refrigeration & None fridge line BUT appropriate shelving once reconstituted Less logistical issues especially must be stored <25C in the community e.g. when Some service users have c/o and used within 4 patient is not home when the cold injections. hours. CPN arrives to administer injection.

Waste Less of an issue as non fridge Waste is an issue especially Could potentially be a line; no re-constitution needed once cold chain is broken or waste issue if not problems with re-constituting. used once Also, if compliance with oral is reconstituted or an issue. compliance with oral is an issue.

Preparation No special instructions: pre- Needs reconstituting. Must Needs to be re- filled syringe. also be removed from fridge constituted with ~30minutes before solvent prior to administration. administration.

Dose interval Monthly (12 injections per year) Two weekly (26 injections per Monthly injection (12 so may be more convenient for year) injections per year). If the service user more than 5 weeks No flexibility in dosing has lapsed before Dosing allows 7 day leeway with recommended next injection, then missed dosages or re- supplementation with scheduling: greater flexibility 2 weeks oral aripiprazole is needed. Service users seem to prefer monthly injections (from feedback).

Strengths 4 strengths 3 strengths 1 strength (although a available *300mg dose maybe given if ADRs from 400mg)

Site of Gluteal or Deltoid Gluteal or deltoid Gluteal (looking at administration deltoid but not licensed yet).

Initiation of Easier initiation Initiation can be ‘complex’ Requires 2 weeks treatment treatment with oral No oral supplementation Requires oral supplementation aripiprazole to allow necessary; reducing for at least 3 weeks. time for LAI to polypharmacy. steady state.

Prescribing guidelines Paliperidone LAI May 2014 V1.0 BLS Final Requires first 2 doses one week apart then monthly thereafter; reduces poly-pharmacy

*1.5mL from same 400mg vial 200mg/mL

References

1. Summary of Product Characteristics (SPC)

2. BNF (66)

3. Paliperidone Long-Acting Injection (Xeplion®): Guidelines for Prescribing and Administration, Sussex Partnership NHS Foundation Trust.

4. Guidelines for the use of Paliperidone Long Acting Injection Birmingham and Solihull Mental Health Foundation Trust Pharmacy Services November 2011

Prescribing guidelines Paliperidone LAI May 2014 V1.0 BLS Final