Download Aripiprazole LAI Prescribing Guidelines

Aripiprazole Long Acting Injection (Abilify Maintena®)
Guidance for Prescribing and Administration
Main points:
1. Aripiprazole Long Acting Injection (‘Aripiprazole LAI’), is indicated for maintenance treatment
of schizophrenia in adult patients stabilised with oral aripiprazole.
2. Aripiprazole LAI may not be used for treatment-resistant schizophrenia, unlicensed
indications or service users intolerant to or unresponsive oral aripiprazole.
3. Aripiprazole LAI may ONLY be newly prescribed by consultant psychiatrists. Other grades
may initiate, but ONLY with direct instruction from their consultant.
4. ALL service users MUST have been on oral aripiprazole for at least 2 to 4 weeks before the
injection is started to establish tolerability and response .
5. The recommended starting and maintenance dose of Aripiprazole LAI is 400 mg once-monthly
i.e. once per calendar month, (not 4-weekly) by deep intramuscular (IM) injection into the
gluteal muscle (no sooner than 26 days after the previous injection).
6. Oral aripiprazole at 10mg-20mg per day must continue for two weeks after the first injection to
maintain therapeutic aripiprazole concentrations during initiation of therapy.
7. As aripiprazole LAI requires oral supplementation for the first 2 weeks (as point 6 above),
consideration must be made for those patients where compliance with oral medication is an
issue, for both clinical and financial reasons.
8. The dose maybe reduced to 300mg a month if 400mg is poorly tolerated (NB: this will incur
waste as only 400mg vial for ALAI exists). No other doses may be used except in those
service users receiving potent enzyme inhibiting drugs (See ‘Special populations’ (page 2) and
SPC for further information).
9. At the recommended dose, aripiprazole LAI costs £220.41 per service user per month. This is
considerably more than older depots such as flupentixol and zuclopenthixol but less than
risperidone and paliperidone LAI (See Appendix 1 for cost comparisons).
10. Practical comparisons with risperidone and paliperidone LAI are given in Appendix 2.
11. For actions for ‘Missed doses’, please see Appendix 3.
12. Administration of aripiprazole LAI requires some special precautions so nursing staff should
familiarise themselves with the instructions as per SPC.
13. Please note, that as a direct delivery service (e.g. Polar Speed) has not been arranged
for Aripiprazole LAI then the VAT exemption for community patients does not apply.
Please consider the cost impact this may have on your locality drug budget before
prescribing,
14. Regular reports will also be run on Ascribe to gauge usage across the Trust and impact on
drug budgets.
15. For ‘Place in Therapy’ please see next section.
Prescribing Guidelines May 2014 Final V1.1 BLS
Place in therapy
The following criteria must be fulfilled BEFORE Aripiprazole LAI is prescribed:
1. ALL service users MUST have been on oral aripiprazole for at least 2 to 4 weeks before
the injection is started to establish tolerability and response .
2. The service users MUST have a documented proven response and tolerability to oral
aripiprazole
Providing both criteria above are fulfilled (with no ADRs) aripiprazole Long Acting injection (ALAI)
may be a treatment option for those service users where:
1. previous treatment with typical depot antipsychotics or other LAI have not been tolerated
or are contra-indicated
OR
2. there has been documented metabolic disturbances with previous treatment.
As aripiprazole is associated with fewer metabolic disturbances the LAI improves patient
outcomes e.g. in first episode psychosis, due to the more favoured side effect profile.
The Trust will be monitoring outcomes for patients prescribed Aripiprazole LAI. Prescribers (see
‘3’ above) are therefore asked to complete the initiation form (Appendix 4) for each service user,
and send it to the Formulary Pharmacist ([email protected]) then their usual supplying
pharmacy with the first prescription.
Special populations
1. Elderly patients
The safety and efficacy of Aripiprazole LAI in the treatment of schizophrenia in patients 65
years of age or older has not been established.
2. Renal impairment
No dosage adjustment is required for patients with renal impairment..
3. Hepatic impairment
No dosage adjustment is required for patients with mild or moderate hepatic impairment. In
patients with severe hepatic impairment, the data available are insufficient to establish
recommendations. In these patients requiring cautious dosing, oral formulation should be
preferred.
4. Smoking
No dose adjustment is necessary in smokers.
5. Known CYP2D6 poor metabolisers / strong enzyme inhibitors
In patients who are known to be CYP2D6 poor metabolisers, the starting and maintenance
dose should be 300 mg. When used concomitantly with strong CYP3A4 inhibitors the dose
should be reduced to 200 mg. Please see SPC for more information.
Prescribing Guidelines May 2014 Final V1.1 BLS
For those patients prescribed
Aripiprazole LAI 400mg
Strong CYP2D6 or strong
CYP3A4 inhibitors
Adjusted dose
300mg
Strong CYP2D6 and strong
CYP3A4 inhibitors
CYP3A4 inducers
Lithium or Valproate
For those patients prescribed
Aripiprazole LAI 300mg
Strong CYP2D6 or strong
CYP3A4 inhibitors
200mg
Avoid use
No adjustment
necessary
Adjusted dose
200mg
Strong CYP2D6 and strong
CYP3A4 inhibitors
160mg
CYP3A4 inducers
Lithium or Valproate
Avoid use
Examples of interacting drug
CYP2D6 e.g. Fluoxetine,
paroxetine and quinidine.
CYP3A4 e.g. HIV protease
inhibitors, ketoconazole
CYP2D6 e.g. Fluoxetine,
paroxetine and quinidine.
CYP3A4 e.g. HIV protease
inhibitors, ketoconazole
Examples of interacting drug
CYP2D6 e.g. Fluoxetine,
paroxetine and quinidine.
CYP3A4 e.g. HIV protease
inhibitors, ketoconazole
CYP2D6 e.g. Fluoxetine,
paroxetine and quinidine.
CYP3A4 e.g. HIV protease
inhibitors, ketoconazole
e.g. Carbamazepine, rifampicin,
phenytoin, St Johns Wort,
No adjustment
necessary
Dosage adjustments should be done in patients taking concomitant strong CYP3A4 inhibitors
or strong CYP2D6 inhibitors for more than 14 days.
Upon discontinuation of the CYP2D6 or CYP3A4 inhibitor, the dosage of Aripiprazole LAI should
be increased to the dose prior to the initiation of the concomitant therapy. When weak inhibitors of
CYP3A4 (e.g.diltiazem) or CYP2D6 (e.g. escitalopram) are used concomitantly with this medicinal
product, modest increases in plasma aripiprazole concentrations may be expected.
Prescribing Guidelines May 2014 Final V1.1 BLS
Appendix 1:
Cost comparison of Long-Acting and depot antipsychotic injections (Drug Tariff March 2014).
Name
Aripiprazole LAI
Paliperidone LAI
Risperidone LAI
Olanzapine LAI
Dose
400mg monthly
50mg monthly
75mg monthly
100mg monthly
150mg monthly
25mg 2- weekly
37.5mg 2-weekly
50mg 2-weekly
150mg 2- weekly
300mg 4-weekly
210mg 2-weekly
405mg 4-weekly
300mg 2 weekly
Traditional depot antipsychotics:
Flupentixol
200mg every 2 weeks
Cost per unit
£ 220.41 x 12
£ 183.92 x 12
£ 244.90 x 12
£ 314.07 x 12
£ 392.59 x 12
£ 79.69 x 26
£111.32 x 26
£142.76 x 26
£ 142.76 x 26
£ 222.64 x13
£ 142.76 x 26
£ 285.52 x 13
£ 222.64 x 26
Cost per year
£ 2644.92
£ 2207.04
£ 2938.80
£ 3768.84
£ 4711.08
£ 2071.94
£ 2894.32
£ 3711.76
£3711.76
£2894.32
£3711.76
£3711.76
£5788.64
£19.52 x 26
£ 507.52
(200mg/mL)
Fluphenazine
100mg every 2 weeks
Haloperidol
200mg every 4 weeks
£8.79 x 26
£ 228.54
(100mg/mL)
£10.10 x 13
£ 131.30
(100mg/mL x 2)
Pipotiazine
200mg every 4 weeks
Zuclopenthixol
500mg every 2 weeks
£53.30 x 13
£ 692.90
(50mg/mL.2x2mL amp)
£7.44 x 26
(500mg/mL)
Prescribing Guidelines May 2014 Final V1.1 BLS
£ 193.44
Appendix 2:
Practical comparisons of Aripiprazole LAI with Risperidone and Paliperidone LAI.
Paliperidone Long Acting
Injection (PLAI)
Presentation
Storage
Preparation
Dose interval
Aripiprazole Long
Acting Injection
(ALAI)
Pre-filled syringe: no
reconstitution needed; may also
help reduce anxiety by service
user.
Vial & solvent for
reconstitution requiring more
nurse time.
Vial & solvent for
reconstitution
requiring more nurse
time.
None fridge line
Requires refrigeration &
appropriate shelving
None fridge line BUT
once reconstituted
must be stored <25C
and used within 4
hours.
Less logistical issues especially
in the community e.g. when
patient is not home when the
CPN arrives to administer
injection.
Waste
Risperidone Long Acting
Injection (RLAI)
Some service users have c/o
cold injections.
Less of an issue as non fridge
line; no re-constitution needed
Waste is an issue especially
once cold chain is broken or
problems with re-constituting.
Also, if compliance with oral is
an issue.
Could potentially be a
waste issue if not
used once
reconstituted or
compliance with oral is
an issue.
No special instructions: prefilled syringe.
Needs reconstituting. Must
also be removed from fridge
~30minutes before
administration.
Needs to be reconstituted with
solvent prior to
administration.
Monthly (12 injections per year)
so may be more convenient for
the service user
Two weekly (26 injections per
year)
Monthly injection. If
more than 5 weeks
has lapsed before
next injection, then
supplementation with
2 weeks oral
aripiprazole is
needed.(see ‘missed
doses’ below).
Dosing allows 7 day leeway with
missed dosages or rescheduling: greater flexibility
No flexibility in dosing
recommended
Service users seem to prefer
monthly injections (from
feedback).
Strengths
available
4 strengths
3 strengths
1 strength (although a
*300mg dose maybe
given if ADRs from
400mg)
Site of
administration
Gluteal or Deltoid
Gluteal or deltoid
Gluteal (looking at
deltoid but not
licensed yet).
Initiation of
treatment
Easier initiation
Initiation can be ‘complex’
No oral supplementation
necessary; reducing
Requires oral supplementation
for at least 3 weeks.
Prescribing Guidelines May 2014 Final V1.1 BLS
Requires 2 weeks
treatment with oral
aripiprazole to allow
time for LAI to reach
polypharmacy.
steady state.
Requires first 2 doses one week
apart then monthly thereafter;
reduces poly-pharmacy
*1.5mL from same 400mg vial 200mg/mL
Appendix 3
Missed doses
If 2nd or 3rd dose is missed and time of last
injection is:
Action
4 weeks and 5 weeks
The injection should be administered as soon as
possible, then monthly administration resumed.
5 weeks
Re-start concomitant oral aripiprazole for 14 days
with next depot and resume monthly schedule.
If 4th or subsequent doses are missed (i.e.
after steady state has been reached) and
time since last injection is:
Action
4 weeks and 6 weeks
The injection should be administered as soon as
possible, then monthly administration resumed.
6 weeks
Re-start concomitant oral aripiprazole for 14 days
with next depot and resume monthly schedule.
Prescribing Guidelines May 2014 Final V1.1 BLS
Appendix 4:
Aripiprazole Long Acting Injection: Initiation form
To be completed by the consultant psychiatrist or under direct instruction from consultant psychiatrist.
Patients details:
Name
Rio Number
Gender
DOB
Consultant
Current ICD-10 diagnosis
Patient setting (please delete)
In-patient
Out-patient
under CTO
Number of hospital admissions in last 2 years
If inpatient, date admitted: …../…../ …..
Reason for request of Aripiprazole LAI.
Have other depot/ LAI preparations been considered?
Y
N
I wish to prescribe Aripiprazole LAI because (please tick all that apply):
The service user has developed unacceptable side effects from (delete as appropriate)
Typical depot
Paliperidone LAI
Risperidone LAI
A formal rating scale has been used and outcomes documented in the notes.
There are problems with oral compliance that are likely to be improved by a long-acting
injection.
To avoid the need for oral medication (i.e. convenience)
Low risk of weight gain
Low risk of hyperprolactinaemia
Low risk of cardiac effects
Low risk of metabolic adverse effects
Poor response from other antipsychotics
Please list others already tried:
Other : Please give details
Who will be administering aripiprazole LAI and where?
Current regular antipsychotic(s) and dose:
Declaration
1. I confirm that arrangements are in place for administration of aripiprazole LAI on a monthly
basis.
2. I confirm that the patient will be closely monitored for efficacy and tolerability using the
Glasgow Antipsychotic Side-effect Scale (GASS) and that a full assessment will be
undertaken at 3 months,6 months and regularly thereafter.
3. I confirm that the patients care-coordinator is aware that they may be contacted to
organise the completion of a feedback form so that data on the use of the drugs can be
collected and evaluated.
4. I understand that the Trust will remain responsible for prescribing until agreement is
reached between the Trust and local CCGs. Referral cannot be made to primary care for
continuation of prescribing, even if local arrangements are in place for GP prescribing of
other LAI / depot antipsychotic injections, unless a shared care agreement has been
approved for that CCG.
Name of initiating Senior
psychiatrist
Signature
Grade
Date
Thank you for completing this form. Please send completed form to the Formulary Pharmacist
[email protected].
For supplying pharmacies: Please ensure that a copy of this form is received with the first prescription for aripiprazole LAI
before it is supplied & keep a copy filed in the dispensary.
Prescribing Guidelines May 2014 Final V1.1 BLS
References
1.
2.
3.
4.
The Summary of Product Characteristics (SPC)
BNF (66)
Sussex Partnership, NHS Foundation Trust (CMHP UK)
Taylor D, South London and Maudsley Hospital, Guidance on Aripiprazole Long Acting
Injection.
5. AWP Product Evaluation for Aripiprazole LAI (Presented at ‘Medicines Optimisation
Group’ 24.1.14)
Prescribing Guidelines May 2014 Final V1.1 BLS