Quetiapine extended-release* tablets (Seroquel XR) were added to the Schedule of Pharmaceutical Benefits on 1 November 2008 as a streamlined authority-required listing for schizophrenia.
The extended-release tablets come in different strengths to those of the existing immediate-release tablets, and dosing and administration has changed slightly. Prescribers will need to instruct patients carefully to prevent confusion between the two formulations. There is no compelling reason to switch people who are currently stable on quetiapine immediate-release tablets to extended-release tablets.
Quetiapine extended-release tablets are not currently indicated or PBS listed for mania. The existing streamlined authority listings of immediate-release quetiapine for schizophrenia and acute mania remain unchanged. See theNPS RADAR brief item Quetiapine (Seroquel) PBS listed for acute mania for details of this listing.
* This formulation is referred to as 'modified release' in the TGA-approved product information and the Schedule of Pharmaceutical Benefits.
There is no evidence that extended-release tablets improve efficacy, tolerability or adherence
Once-daily dosing with quetiapine extended-release tablets is equivalent to twice-daily dosing with quetiapine immediate-release tablets, e.g. quetiapine extended release 600 mg once daily is equivalent to quetiapine immediate release 300 mg twice daily. Comparative trials have found no difference in efficacy or tolerability between the 2 formulations, and have not assessed the relationship between dosing frequency and adherence.1,2
Some people may prefer once-daily dosing with the extended-release tablets, but immediate-release tablets give greater flexibility in dosing and in timing with respect to meals.
When switching is appropriate, patients can switch directly from twice-daily immediate-release tablets to an equivalent total daily dose of the extended-release tablets, taken once daily.3 Some people may need dose adjustment.3
The Pharmaceutical Benefits Advisory Committee (PBAC) found that the extended-release tablets were as effective as quetiapine immediate-release tablets (Seroquel) for no greater cost.4
Quetiapine extended-release tablets are taken once daily
People may prefer evening dosing to minimise any daytime sleepiness. Extended-release tablets should not be chewed, crushed or split.3
Extended-release quetiapine should not be taken with food. In one study using this formulation, a high-fat meal increased the peak blood levels of quetiapine and overall absorption.3 Raised blood levels of quetiapine may increase the risk of adverse effects.
Provide clear information to patients to help avoid confusion
Most of the extended-release tablets have different shapes and markings to the immediate-release tablets (see Table 1). Note however that the quetiapine extended-release 400 mg tablet has a similar appearance to the quetiapine immediate-release 300 mg tablet.
Table 1 Appearance of immediate-release and extended-release quetiapine tablets
If switching from another antipsychotic or from quetiapine immediate-release tablets, provide written instructions about how many tablets to take each day and at what time, and remind the patient to dispose of any old medicines that are no longer needed.
Discuss the Seroquel XR consumer medicine information (CMI) leaflet with the patient.
Dose escalation over 2–3 days is recommended for some people
The manufacturer has introduced a faster dose escalation protocol with the extended-release formulation, although some people may require slower titration. For people not currently taking an antipsychotic, the manufacturer recommends dose escalation over 2–3 days, with a dose of quetiapine extended release 300 mg on the first day, 600 mg on the second day and up to 800 mg on subsequent days.3 The usual maintenance dose consists of 2 × 300 mg tablets, taken once daily.
Start elderly people and people with hepatic impairment on a lower dose of quetiapine extended release 50 mg daily. Increase in increments of 50 mg to an effective dose, monitoring carefully for adverse effects, at a rate appropriate to the patient.3
Faster dose escalation was not associated with a significant increase in adverse effects in people with schizophrenia (mean age 34) and no serious comorbidities.1 Dizziness and somnolence were the most commonly reported treatment-related adverse effects in the first week of treatment (see Table 2), but there were few adverse events that led to discontinuation.
Table 1 Incidence of selected adverse events during week 1 of treatment1
||Quetiapine target total daily dose|
Extended release(fast dose escalation)
Immediate release(conventional dose escalation)
(n = 118)
(n = 113)
(n = 121)
(n = 123)
Switching patients from other antipsychotics to quetiapine extended-release tablets requires tailoring of doses to the individual's response — there is insufficient evidence to support any particular protocol. Gradual discontinuation of the old drug may be appropriate, but in all cases minimise the period of overlapping antipsychotic administration.5
The approved dose range differs from that of the immediate release tablets
Adjust the dose within the usual effective range of 400–800 mg daily, depending on the clinical response and adverse effects.3 Elderly or frail patients, people with hepatic impairment, or people with a predisposition to hypotensive reactions may require a lower target dose.3,5 Daily doses higher than 600 mg have not shown greater efficacy in trials, although some individuals may benefit from a higher dose.6 Note that the dose range of 400–800 mg daily for quetiapine extended release differs from the approved dose range for quetiapine immediate release of 150–750 mg daily for schizophrenia.7
- Kahn RS, Schulz SC, Palazov VD, et al. Efficacy and tolerability of once-daily extended release quetiapine fumarate in acute schizophrenia: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2007;68:832-42. [PubMed]
- M\u00f6ller HJ, Johnson S, Mateva T, et al. Evaluation of the feasibility of switching from immediate release quetiapine to extended release quetiapine fumarate in stable outpatients with schizophrenia. Int Clin Psychopharmacol 2008;23:95-105. [PubMed]
- Astra-Zeneca Pty Ltd. Quetiapine modified release product information. 23 April 2008.
- Australian Government Department of Health and Ageing. July 2008 PBAC outcomes: positive recommendations. http://www.health.gov.au/internet/main/publishing.nsf/Content/pbacrec-jul08-positive (accessed 24 September 2008).
- AstraZeneca Pharmaceuticals LP [USA]. Seroquel XR (quetiapine fumarate) extended-release tablets Prescribing Information. April 2008. http://www.fda.gov/cder/foi/label/2008/022047s013lbl.pdf (accessed 23 September 2008).
- AstraZeneca UK Limited. Seroquel XL summary of product characteristics. 10 September 2008. http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=21175 (accessed 23 September 2008).
- Astra-Zeneca Pty Ltd. Quetiapine product information. 13 February 2008.