1. Project Implementation Work Stream
Switching Quetiapine XL (Slow Release) to IR (Immediate Release) Formulation
Project Implementation Work Stream
on behalf of NSFT D & T
(Asta R Prajapati, Stuart Maddock, Siri Robling, Joan Bufton, Jenny Walker)

2. Contents Background Pharmacology Cost Comparison
NSFT Guidance to switch to IR
D & T recommendation
Further info

3. Background
NSFT D & T Committee approved Prescribing Information on switching patients from quetiapine XL to IR in Mar 2017
May 2017: D & T approved Implementation Plan
1st Sept 2017: All patient requiring initiation of quetiapine should be prescribed IR except in exceptional cases (e.g. for initial 3 days for acute treatment of schizophrenia or mania to reduce in-patient bed days). All patient on quetiapine XL should be considered for switching to IR.
1st Dec 2017: Quetiapine XL will be non-formulary and thus any patient still needing XL will require non-formulary drug approval by D & T.
Rationale: See Prescribing Information for details. But the essence is “No expected significant efficacy difference but significant cost difference between the TWO formulations”
Quetiapine patent expired in March The cost of IR formulation decreased by ≈ 95% but cost of XL remained almost the same (although some XL formulation are cheaper than others but still hugely expensive than IR).
Quetiapine developed in 1985 launched in 1997 by AstraZeneca.
1997 – IR Schizophrenia
2009 – IR - Bipolar
XL Preparation released in 2009 for schizophrenia and Bipolar
Bipolar Depression
UK patent expired 2012

4. Pharmacology
Quetiapine is an SGA with relatively similar chemical structure to olanzapine and clozapine. See Handy Chart Comparing Antipsychotics
Suggested Similar Efficacy Kahn 2007 :
Suggested similar adverse effects (AEs) profile but possibly slightly higher sedation, orthostatistic hypotension and tachyardia with IR Meulien However they are variable and dose dependent, e.g. Sedation with 400mg/day IR = 0.8% patients cf 10.6% patients in XL 400mg/day.
Adverse effect may be particularly pronounced during initial period SO advise patient to be vigilant for first 2 weeks (e.g. careful while standing up, driving etc.)
End-Point IR 400mg / day XL 400mg / day
PANSS Total Score
CGI Response rate 75.6% 73.9%
Also Treatment Satisfaction Questionnaire of Medication (TSQM) score on effectiveness and convinience did not seem significant .
Although overall satisfaction score on TSQM was slightly lower in IR 63.0 (19.7) 58.9 (21.1) P= – Ref: Schizophr Res. 2015;
Formulation Sedation Orthostatic Hypotension Tachycardia
IR % % %
XL % % %
Ref: Meulien 2010

5. Pharmacology: Mechanism of Action
Quetiapine is an atypical antipsychotic with actions mainly on D2 and 5-HT2 antagonism.
Highest Affinity: H1, A1
Moderate: 5-HT2a, M1, 5-HT 7
Lowest: 5-HT2c, D2, 5-HT1a.
It has a 5-HT1a partial agonistic actions, which along with it actions on 5-HT7, 5- HT2c contribute to its anti- depressant effects
Nor-quetiapine which is the active metabolite of quetiapine, has a unique pharmacologic property.
It inhibits adrenalin transport. Thus contributing to the anti-depressant effects of quetiapine.

6. Pharmacokinetics Metabolism: Primarily hepatic by CYP 3A4.
Excretion: Urine (Major), Faeces (Minor), Unchanged (1%)
Half-Life: quetiapine ≈ 7 hours and nor-quetiapine ≈ 12 hours
Time to Peak (Tmax): IR ≈ 1.5 Hrs, XR ≈ 6 Hrs
C Max is the same although time is 1.5hrs vs 6hrs
Receptor occupancy at D2 site is not linked with plasma levels.
Plasma levels correlate with histamine and alpha receptors.
Arithmetic Mean Plasma Quetiapine Concentrations (SEM) Measured Over a 24-Hour Dosing Interval for Quetiapine IR and XR.
(Ref: Figuera et al. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33: )

8. Licensed Indication

9. Please check BNF for details.
Dosing for adult
Formulation
Schizophrenia
Mania
Quetiapine IR
(Oral)
25 mg BD day 1, 50 mg BD day 2, 100 mg BD day 3, 150 mg BD day 4, then, adjusted according to response, maximum 750 mg per day.
50 mg BD day 1, 100 mg BD day 2, 150 mg BD day 3, 200 mg BD day 4, then adjusted in steps of up to 200 mg daily, usual dose 400–800 mg daily in 2 divided doses; max. 800 mg per day.
Quetiapine XL
300 mg OD day 1, 600 mg OD day 2, then, adjusted according to response, max. 800 mg per day.
300 mg OD day 1, 600 mg OD day 2, then adjusted according to response, usual dose 400–800 mg once daily.
The rate of dose titration may need to be slower and the daily dose lower in elderly patients.
Dosing is different for bipolar depression or major depression.
Please check BNF for details.

10. Which one should we buy for our pain relief?
Nurofen ≈ £6.5 / 24 tablets
Generic ≈ £0.78 / 36 tablets

11. Cost Difference of ≈ £68.4K – £200K
Cost Comparison
Graph 1: Cost comparison between Quetiapine XL and equivalent dose of IR
The prices are from the Drug Tariff Nov 2016 and are based on the costs for 30 days treatment at the equivalent dose.
Annual cost of quetiapine XL 600mg/day per 100 patient is ≈ £72K - £204K compared to ≈ £3600 for 600mg IR (Ref: BNF 2017)
Cost Difference of ≈ £68.4K – £200K

12. Many other Trusts, including most of our neighbouring mental health Trusts, have already been advising the switch.

13. Switching Guidance Current dose of quetiapine XL
Quetiapine IR dosing options (See Guidance for details)
For those who are tolerating quetiapine well and do not have compliance concerns
For those who are (or at risk of ) experiencing sedation or postural hypotension following the switch#
For those who are tolerating quetiapine well but have compliance concerns.*
400mg XL OD
200mg BD
150mg OM, 250mg ON
400mg ON
300mg XL OD
150mg BD
100mg OM, 200mg ON
300mg ON
200mg XL OD
100mg BD
50mg OM, 150mg ON
200mg ON
150mg XL OD
50mg OM, 100mg ON
150mg ON
100mg XL OD
50mg BD
25mg OM, 75mg ON
100mg ON
50mg XL OD
25mg BD
 25mg BD OR 50mg ON
50mg ON

14. NSFT D & T Recommendation
From 1st Aug 2017
All patients should be initiated on IR (For exception see Guidance)
Prescribers are requested to consider switching patients on quetiapine XL to IR – Discuss with patient (see Patient information leaflet in the Guidance)
Any patient who cannot tolerate or have specific clinical need please complete Non-Formulary Request form (with specific details of intolerance or clinical need) and send to Please consider this before Nov Also, ensure to record the intolerance or specific clinical need on Lorenzo under medication Alert.
From 1st Nov 2017
Quetiapine XL will be non-formulary and prescribing of XL should continue only if Non-formulary Request form has been approved by D & T.

15. Further information
See “Prescribing Guidelines > Quetiapine XL to IR switch” on the West Suffolk CCG website for
Prescribing Information for switching Quetiapine XL to IR and Implementation Plan which include some FAQs.
This power point presentation for education, training and raising awareness
For medicines information and related query
D & T related queries

16. Quetiapine – Update on costs (1)
Strength and formulation
Feb 2016
Dec 2017
Jan 2018
25mg tablets IR
£1.24
£0.91
£13.84
100mg tablets IR
£2.07
£1.62
£52.22
150mg tablets IR
£2.58
£2.27
£61.75
200mg tablets IR
£2.89
£51.30
300mg tablets IR
£3.52
£3.31
£73.45
50mg tablets MR
£67.66
150mg tablets MR
£113.10
200mg tablets MR
300mg tablets MR
£170.00
400mg tablets MR
£226.20
Drug Tariff costs, for 60 tablets (MR tablets are od, IR usually bd)

17. Quetiapine – Update on costs (2)
Drug Tariff, January 2018
Daily dose
Cost per month IR
Cost per month MR
50mg
£27.68
£67.66
100mg
£104.44
£135.32
200mg
£102.60
£113.10
300mg
£146.90
£170.00
400mg
£205.20
£226.20
The prices need to stabilise again before a decision can be made regarding cost-effective prescribing choices