SECTION 2: TREATMENT OF PSYCHOSIS. Formulary and Prescribing Guidelines

Transcription

1 SECTION 2: TREATMENT OF PSYCHOSIS Frmulary and Prescribing Guidelines

2 2.1 Principles f Antipsychtic Prescribing Where pssible, chice f antipsychtic shuld be made jintly by the patient and the clinician respnsible fr treatment based n an infrmed discussin f the relative benefits f the drugs and their side-effect prfiles. Where mre than ne drug is apprpriate, an antipsychtic f lw acquisitin cst shuld be selected. As Required (PRN) antipsychtics shuld nly be prescribed when abslutely necessary. On-call dctrs shuld prescribe nce nly dses f antipsychtics n the Once Only sectin f the medicatin chart and nt rutinely add them t the PRN side f the card. Ward dctrs shuld nly prescribe PRN antipsychtics fr a maximum f 6 dses r 7 days, whichever is the shrter. Once this perid has expired, treatment shuld be reviewed by a senir dctr and the requisite changes made t the regular sectin f the medicatin chart. PRN antipsychtics shuld nt be autmatically re-written. PRN intramuscular antipsychtics may be emplyed when ral (PO) dsing is nt pssible. The intramuscular dse (IM) is usually lwer than the crrespnding ral dse (due t the absence f first pass effect). Fr example, 6 mg halperidl IM is cnsidered equivalent t 10 mg halperidl PO. Separate prescriptins shuld be written fr PO and IM antipsychtics. D nt write PO/IM fr any antipsychtic medicatin always specify the rute f administratin and the crrespnding dse separately. PRN dses f intramuscular antipsychtic medicatin shuld be reviewed every seven days. Detailed infrmatin n the treatment f psychsis in children and adlescents can be fund in sectin 12. Further guidance n prescribing fr lder adults and fr antenatal/pstnatal service users can be fund in sectin 11 and sectin 20, respectively. Peple with brderline r antiscial persnality disrders are prescribed antipsychtic r sedative medicatin nly fr shrt-term crisis management r treatment f cmrbid cnditins. 2.2 Apprved Drugs in the treatment f Psychsis in Adults Drug 1 Frmulatin 2 Typical Antipsychtics (First Generatin Antipsychtics (FGA)) Halperidl Chlrprmazine Flupentixl Sulpiride Trifluperazine Zuclpenthixl Caps 500 micrgrams Tabs 1.5mg, 5mg, 10mg, Liquid 2mg/ml Injectin 5mg/ml Tabs 25mg, 50mg,100mg Liquid 25mg/5ml, 100 mg/5ml Tabs 3mg Tabs 200mg, 400mg Liquid 200mg/5ml Tabs 1mg,5mg Liquid 1mg/5ml, 5mg/5ml Tabs 2mg, 10mg, 25mg Injectin, Zuclpenthixl acetate 50 mg/ml (Acuphase) Cmments

3 Drug 1 Frmulatin 2 Atypical Antipsychtics (Secnd Generatins Antipsychtics (SGA)) Risperidne Amisulpride Aripiprazle Tabs 0.5mg, 1mg, 2mg, 3mg, 4mg, 6mg Liquid 1mg/ml Ordispersible tablet s 0.5mg, 1mg, 2mg, 3mg, 4mg Tabs 50mg, 100mg, 200mg, 400mg Liquid 100mg/ml Tabs 5mg, 10mg, 15mg, 30mg Ordispersible tabs 10 mg, 15 mg Oral slutin 1mg/ml Injectin 7.5mg/ml (immediate release) Clzapine Tabs 25mg, 100mg (Cnsultant initiatin nly) Olanzapine Quetiapine Dept Injectins Flupentixl decanate Tabs 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg Ordispersible tabs 5mg, 10mg, 15mg, 20mg Injectin, 5 mg/ml (nn-dept) Tabs 25mg,100mg, 150mg, 200mg, 300mg XL tabs 50mg, 200mg, 300mg, 400mg. Injectin 20mg/ml, 40mg/2ml, 50mg/0.5ml, 100mg/ml, 200mg/ml Patients shuld be transferred t standard frmulatin as sn as pssible and always prir t discharge Patients shuld be discharged n standard release Fluphenazine decanate Injectin 25mg/1ml,100mg/ml New patients nt t be initiated n treatment Halperidl decanate Risperidne (Risperdal Cnsta ) Injectin 50mg/ml, 100mg/ml (Lng-acting) Injectin 25mg, 37.5mg, 50mg (Cnsultant initiatin nly) Aripiprazle (Abilify Maintena ) (Lng acting ) Injectin 400mg (Cnsultant initiatin nly) Zuclpenthixl decanate Injectin 200mg/ml, 500mg/ml Cnsultant initiatin Initiatin frm t be cmpleted and sent t pharmacy Cnsultant initiatin Initiatin frm t be cmpleted and sent t pharmacy Paliperidne Xeplin (mnthly) 50mg, 100mg, 150mg PFS Cnsultant initiatin Initiatin frm t be cmpleted and sent t pharmacy Trevicta (3 mnthly) 175mg, 263mg, 350mg, 525mg Patients shuld be adequately treated with mnthly paliperidne palmitate injectable fr fur mnths r mre, and nt require dse adjustment.

4 SGAs highlighted in bld are assciated with lwer acquisitin csts. If mre than ne SGA is apprpriate fr a particular service user, ne with a lw acquisitin cst shuld be prescribed t ensure cst effectiveness within the health ecnmy. Clinicians are remained that Quetiapine XL still remains cnsiderably mre expensive than the standard release tablet. It has been agreed at MMG/CCGs that suitable service users shuld be transferred t standard release frmulatins as highlighted in appendix NICE Clinical Guidelines NICE CG178, Feb Schizphrenia in ADULTS 9 NICE CG178 cvers treatment and management f schizphrenia and related disrders (schizaffective disrder, schizphrenifrm disrder, and delusinal disrder) in adults (f 18 years and lder). This guideline des nt relate t late-nset schizphrenia. Fr patients with newly diagnsed schizphrenia, ral antipsychtic medicatin shuld be ffered when deemed necessary. The chice f antipsychtic medicatin shuld be made by the service user and healthcare prfessinal tgether, taking int accunt the views f the carer if the service user agrees. Prvide infrmatin and discuss the likely benefits and pssible side effects f each drug, including: metablic (including weight gain and diabetes) extrapyramidal (including akathisia, dyskinesia and dystnia) cardivascular (including prlnging the QT interval) hrmnal (including increasing plasma prlactin) ther (including unpleasant subjective experiences). D nt use lading dses f antipsychtics and d nt initiate regular cmbinatin antipsychtic therapy. (Only use cmbinatins f antipsychtics fr shrt perids, e.g. during change-ver f agents). An ECG shuld be dne if: The patient has a specific cardivascular risk (including elevated BP), r an established persnal histry f cardivascular disease; the service user is being admitted as an inpatient This is a baseline requirement specified in the SPC Upn initiatin f an antipsychtic (which shuld be cnsidered as an individual therapeutic trial) - recrd indicatin(s), expected benefits and risks, and estimate a time interval fr a change in symptms (and emergence f side-effects). Start with a dse at the lwer end f the licensed range and titrate upwards slwly within the dse range in the BNF r SPC. Recrd (with justificatin) the use f an unlicensed dsage(s) range utside that specified in the BNF/SPC. Mnitr and recrd thrughut treatment (and especially during titratin) efficacy (including changes in symptms and behaviur), side-effects, adherence and physical

5 health. Recrd ratinale fr cntinuing, changing r stpping medicatin (and the effects f such changes). Allw a trial f an antipsychtic at ptimum dsage fr at least 4-6 weeks. Be aware f any nn-prescribed therapies (cmplimentary therapies), and usage f tbacc, alchl, illicit drugs and nn-prescriptin medicatins by the patient. Discuss with the service user any pssible interference that the afrementined may have with the effects f prescribed medicatins. Discuss als the safety and efficacy f nn-prescribed therapies. Review every seven days r after six dses PRN antipsychtic medicatin with respect t indicatin, frequency f administratin, benefits, and side-effects. Calculate whether the antipsychtic dse (regular and PRN) is abve BNF/SPC maxima. During the early pst-acute phase, service users shuld be infrmed abut the high risk f relapse if medicatin is stpped within 1-2 years. If it is decided t withdraw medicatin, this must be dne gradually with regular mnitring f signs and symptms f relapse fr at least 2 years after withdrawal. Fr patients presenting with an acute episde (exacerbatin r recurrence) an ral antipsychtic shuld be ffered (taking int accunt the clinical respnse and side effects f previus and current medicatin). RT (Rapid Tranquillisatin) shuld be ffered t peple wh pse an immediate threat t themselves r thers during an acute episde (please see NICE CG10, EPUT prcedural guideline CLPG52 r sectin 8 f this frmulary fr further infrmatin.) NICE CG120 March Psychsis with c-existing substance misuse 8 This guideline cvers the assessment and management f adults and yung peple (aged 14 years and lder) wh have a clinical diagnsis f psychsis with c-existing substance misuse. CG 120 makes the fllwing recmmendatins in relatin t the use f antipsychtics fr this specific grup. Antipsychtics shuld be used in accrdance with NICE CG178 9 (schizphrenia) r NICE CG185 (biplar disrder, sectin 3) because there is n evidence fr any differential benefit fr ne antipsychtic ver anther fr peple with psychsis and cexisting substance misuse. Use dept/lng acting injectable antipsychtics accrding t NICE CG178 9 in managing cvert nn-adherence with treatment f psychsis and nt as a specific treatment fr psychsis and cexisting substance misuse. When prescribing medicatin fr adults and yung peple with psychsis and cexisting substance misuse: Take int accunt the level and type f substance misuse, especially f alchl, as this may alter the metablism f prescribed medicatin, decrease its effectiveness and/r increase the risk f side effects Warn the persn abut ptential interactins between substances f misuse and prescribed medicatin Discuss the prblems and ptential dangers f using nn-prescribed substances and alchl t cunteract the effects r side effects f prescribed medicatin

6 2.3 Relative Side-Effects f Antipsychtics (Typical and Atypical) 5 Where pssible, the chice f antipsychtic shuld be made jintly by the patient and the clinician respnsible fr treatment based n an infrmed discussin f the relative benefits f the drugs and their side-effect prfiles (see table belw/verleaf). A frmalised tl such as LUNSERS shuld be used t capture details f side effects experienced. Additinal tls such as the Abnrmal Invluntary Mvement Scale (AIMS), r the Simpsn Angus Scale may be necessary if there is evidence f tardive dyskinesia. Where mre than ne drug is apprpriate, an antipsychtic f lw acquisitin cst shuld be chsen. Other side-effects nt mentined in the table d ccur. Refer t prescribing infrmatin (SPC fr individual drug) and discuss with patient and/r carer as necessary/relevant. Fr example, when prescribing chlrprmazine warn f its ptential t cause skin phtsensitivity and the need t use sunscreen. The table belw (adapted frm Maudsley, 12 th editin illustrates an apprximatin f relative side effects frm available evidence.) Drug Antichlinergic Diabetes EPSE Hyptensin Sedatin Weight Gain Prlactin elevatin Amisulpride Aripiprazle / /- -- Chlrprmazine Clzapine Flupentixl Fluphenazine Halperidl + +/ Olanzapine / Perphenazine + +/ Quetiapine Risperidne Sulpiride Trifluperazine +/- +/ Zuclpenthixl little + lw / transient ++ mderate +++ high incidence, 2.4 Physical Health Mnitring f Adults taking Antipsychtics 4 Peple with psychsis r schizphrenia, especially thse taking antipsychtics, shuld be ffered a cmbined healthy eating and physical activity prgramme. If a persn has rapid r excessive weight gain, abnrmal lipid levels r prblems with bld glucse management, ffer interventins in line with relevant NICE guidance (see Obesity [NICE clinical guideline 43], Obesity: identificatin, assessment and management f verweight

7 and besity in children, yung peple and adults [Nice Clinical Guideline 189],Lipid mdificatin [NICE clinical guideline 67], Preventing type 2 diabetes [NICE public health guidance 38]) and Maintaining a healthy weight and preventing excess weight gain amngst adults and children NG7. See Appendix 1 fr details f physical health mnitring required. 2.5 High Dse Antipsychtic Therapy (HDT) 1 The prescribing f high dse antipsychtics ccurs in tw ways: A single antipsychtic prescribed at a dse in excess f the maximum BNF recmmended dse The cmbined use f tw r mre antipsychtics where the ttal f the individual dses, expressed as a percentage f the BNF maximum recmmended dse, exceeds 100%. High dse antipsychtic therapy shuld be prescribed fllwing the guidance in Appendix 7 f CPG13 using the mnitring tl in Appendix 2 f this dcument. If a patient is being treated in accrdance with Sectin 58 f the Mental Health Act, their T2 r T3 must state the HDT percentage BNF prescribed. POMH-UK has created an easy t use dse cnverter which can aid calculatin: Antipsychtic Equivalent dses 4 Range f values 4 Maximum dse 2 FGAs ral Chlrprmazine Flupentixl Fluphenazine Halperidl Sulpiride Trifluperazine Zuclpenthixl 100mg/day mg/day 3mg/day 2-3mg/day 18mg/day 2mg/day 2-5mg/day 20mg/day 3mg/day 1.5-5mg/day 20mg/day (see BNF) 200mg/day mg/day 2400mg/day 5mg/day 2.5-5mg/day Nne (?30mg/day) 25mg/day 25-60mg/day 150mg/day SGAs ral Amisulpride Aripiprazle Clzapine Olanzapine Quetiapine It is inapprpriate t cvert SGA dses int equivalents since the dserespnse relatinship is usually well defined fr these drugs. 1200mg/day 30mg/day 900mg/day 20mg/day mg/day

8 Antipsychtic Risperidne Equivalent dses 4 Range f values 4 Maximum dse 2 16mg/day (see BNF) Dept Flupentixl decanate Fluphenazine decanate Halperidl decanate 10mg/week 10-20mg/week 400mg/week 5mg/week mg/week 50mg/week 15mg/week 5-25mg/week 300mg/ 4 weeks Zuclpenthixl decanate 100mg/week mg/week 600mg/week There is n evidence t supprt the rutine use f HDT either as a single agent r as cmbinatins f antipsychtics; althugh in a minrity f cases in may prve effective 1. Thus, the implementatin f such therapy shuld nly be after evidence-based strategies have failed and where diagnsis has been re-cnfirmed, adherence t medicatin has been verified, adjuvant medicatin has been ptimised (fr example, antidepressants and md stabilisers), akathisia has been dismissed and substance misuse has been eliminated. POMH-UK has prduced an antipsychtic dsage ready reckner t aid the calculatin f ttal daily prescribed antipsychtic dse as a percentage f the BNF maximum. This can be dwnladed frm the Pharmacy and Medicines Management pages f the Trust intranet r printed cpies btained frm Pharmacy. HDT shuld nly be attempted as a carefully mnitred, explicit, therapeutic trial with an individual risk-benefit assessment by a Cnsultant Psychiatrist, in cnsultatin with the clinical team and the patient (and the patient s advcate if the patient s wishes). As HDT is a limited therapeutic trial the dse shuld be reduced back t cnventinal levels after a 3-mnth perid unless the (dcumented) clinical benefits utweigh the risks. Supplementary prescribers are nt permitted t prescribe high dse antipsychtic therapy. The decisin t cmmence a patient n an elective trial f antipsychtic medicatin at a dse higher than the maximum BNF recmmended dse is the respnsibility f the patient's cnsultant. Nn-medical prescribers shuld nt make the decisin t prceed t the use f high dse antipsychtics. The reasn fr the treatment, shuld be dcumented using a high dse therapy (HDT) frm (see Appendix 7, CLPG 13), and the patient be given an explanatin why they are receiving a trial f high dse medicatin. Frms are available n wards and in the pharmacy departments. If an individual patient is nt infrmed then an explanatin as t why that was nt dne shuld be dcumented in the patient's healthcare recrd. Risk factrs t be cnsidered (with dcumentatin) include: Gender (wmen are mre predispsed t QTc prlngatin than men) Increasing age Renal/hepatic functin

9 Drug interactins (either interacting drug inhibits the metablism f the antipsychtic and/r prlngs the QTc itself: fr example, erythrmycin, tricyclic antidepressants, certain antihypertensives (e.g. stall) Established cardiac histry (histry f an MI and/r arrhythmia(s)) Cardivascular risk factrs (histry f smking, heavy alchl ingestin, besity) Electrlyte disturbances (e.g. if patient is n a diuretic). An ECG must be carried ut befre initiating high dse antipsychtic therapy (t establish a baseline and exclude cardiac cntra-indicatins, including QTc prlngatin). Thereafter an ECG shuld be carried ut after a few days and, subsequently every 1-3 mnths 1 (and when clinically indicated; shuld HDT be perpetuated). It is apprpriate t mnitr and recrd urea and electrlytes cncmitantly. Dse increments shuld be given time t take effect and ideally shuld nt be made mre than nce weekly. Regular re-assessment f as required (r prn ) medicatin and its ptential t raise the ttal daily dse f antipsychtic abve the high-dse threshld is required 1. During Rapid Tranquillisatin, the use f HDT shuld be circumvented r minimised by the use f alternative strategies such as: de-escalatin techniques, use f benzdiazepines (instead f antipsychtics), allwing sufficient time fr a clinical respnse between dses, and transferring a patient t a suitable envirnment (with sufficient numbers f adequately skilled staff). If, hwever, HDT has t be used then rutine mnitring f a sedated patient shuld include regular checks f pulse, BP, respiratin, hydratin, and temperature. ECGs shuld be carried ut frequently during dse escalatin, if and when pssible and especially, if parenteral administratin f antipsychtic has been implemented 1.(See CG 52 Pharmaclgical Management f Acutely Disturbed Behaviur) 2.6 Guidance n the use f Clzapine Indicatins Clzapine is indicated fr patients with treatment resistant schizphrenia, wh have nt btained satisfactry clinical imprvement despite the sequential use f the recmmended dses fr 6 8 weeks f at least tw antipsychtic drugs, at least ne f which shuld be an atypical. Currently, all patients must be cmmenced r re-titrated n clzapine as inpatients. Sme patients in the Nrth may be initiated in the cmmunity fllwing liaisn with the Clzapine clinic Treatment Advantages 30% f patients wh have previusly been refractry t treatment imprve significantly after 6 weeks treatment with clzapine, and up t 60% respnd after 1 year Effective in negative symptmatlgy Clzapine is assciated with an extremely lw incidence f EPSEs Disadvantages

10 3% f patients develp neutrpenia, necessitating a regular full bld cunt Higher incidence f seizures cmpared t ther antipsychtics, especially abve 600mg daily Orthstatic hyptensin is cmmn n initiatin necessitating gradual dse titratin, and clse mnitring Significant risk f weight gain Night-time salivatin can cause severe discmfrt Increased risk f mycarditis (1000-fld), and cardimypathy (5-fld) A wide range f ther adverse effects Chice f prprietary brand Clzapine is available in three prprietary brands, Zapnex, Clzaril and Denzapine. Each has its wn database fr mnitring bld-tests, ZTAS, CPMS, and DMS respectively. EPUT patients in Suth Essex shuld be started n Zapnex, and thse in Lutn and Bedfrdshire n Denzapine unless pharmacy advise that they are t cntinue n anther brand. Nrth Essex patients shuld be started n Clzaril Prescriber Registratin Befre prescribing, the clinician respnsible fr treatment must be registered with the relevant clzapine database ZTAS/DMS/CPMS.. Registratin frms may be dwnladed frm Once registered, prescribers will be sent infrmatin detailing hw t access the relevant n-line database Patient Registratin and Initiatin Befre using clzapine, the dctr must cntact the mental health pharmacist with the patient s name, date f birth, race, ward, and any available infrmatin abut previus use f clzapine. The pharmacist/cnsultant will then register the patient, and nce a satisfactry baseline bld test result has als been received, the pharmacist will advise the cnsultant that it is safe t cmmence treatment. Clzapine shuld NOT be written n the prescriptin card until the cnsultant has been infrmed that the registratin prcess has been cmpleted and the bld result is valid. Clzapine shuld nly be initiated in an inpatient envirnment Rutine Bld Tests (full bld cunt) The rutine bld test required when taking clzapine is a full bld cunt (FBC). Tests are taken weekly fr the first 18 weeks f treatment, frtnightly fr the next 34 weeks, then every 4 weeks after ne year. Rutine bld tests shuld wherever pssible be taken early in the week, preferably n Mnday r Tuesday and sent t the labratry fr analysis. The nly exceptin t this is if alternative arrangements are made with the Clzapine clinic. In an emergency r if an urgent test is required, bld shuld be sent t the lcal pathlgy labratry fr immediate analysis, and nt psted.

11 Results are assigned a traffic light style clur cde accrding t the white bld cell (WBC), neutrphil and platelet cunts: Green indicates a nrmal cunt, Amber indicates a lwer cunt than nrmal, and Red indicates a very lw cunt. It is recgnised that nursing staff may ccasinally need t take bld against the patient s cnsent if they are detained under the mental health act. This is a necessary part f treatment and the Mental Health Act Cmmissin has given apprval. In the event f a late, amber r red bld result, ZTAS/DMS/CPMS will send faxes t the registered cnsultant and the pharmacist. The pharmacist will act n late r amber warnings autmatically althugh it is prudent fr the cnsultant r their secretary t cntact the pharmacist t ensure the fax has been received. In the event f a red bld result, the pharmacist will cntact the cnsultant (and clzapine clinic nurse fr Nrth Essex) as sn as the alert is received t discuss the curse f actin. Bld test results requiring urgent actin include: Red result: Stp treatment and seek advice frm pharmacy. Repeat bld test urgently at lcal labratry. Amber result: Repeat bld test within 2-3 days at lcal labratry. Clzapine treatment shuld cntinue, but bld test t be repeated twice a week until green result btained Plasma Clzapine Assays (additinal cst invlved) Plasma clzapine assays are NOT the rutine bld tests required fr treatment maintenance. Hwever, plasma levels f clzapine and nrclzapine can be useful t ptimise treatment and t check cmpliance. Cnsider requesting assay if it suspected levels are nt within desired range r if individual s circumstances change, e.g. smking habit/additin f anther antipsychtic/cncrdance issues. Assays can nly be analysed by a specialist labratry such as Magna Labratries/Kings Cllege and shuld nt be sent t a lcal pathlgy labratry. The dse shuld be adjusted t give plasma clzapine levels in the range micrgrams per litre althugh sme patients may require higher r lwer levels fr ptimum respnse Seizure activity may be mre frequent if plasma clzapine levels rise abve 800 micrgrams per litre and prphylactic valprate shuld be cnsidered in patients fr whm a dse reductin is nt apprpriate. Results are available nline 2 days after assay received fr Beds and Lutn nline Assays will nly be dne at the request f a cnsultant r senir dctr. Every request fr a plasma clzapine assay must be c-rdinated by Pharmacy r the clzapine clinic. An assay can be requested in the fllwing way: Cntact a mental health pharmacist fr advice

12 Cntact the clzapine clinic fr advice Obtain a Magna ( Suth Essex), CPMS (Nrth Essex) r DMS yellw plasma (Bedfrdshire & Lutn) bld test kit and patient s barcde labels Take bld 12 hurs (+/- 1 hur) after the night time dse (trugh sample) The day befre the assay, mve any afternn / evening dse f clzapine t 10pm On the day f the assay, pstpne any mrning dse f clzapine and take bld sample (at least 2ml) between 9am and 11am. The patient shuld then take their mrning dse and cntinue as usual. Cmplete dcumentatin in kit Attach cmpleted patient s barcde labels t bld tube and frm Cmplete time and date f previus dse, time and date sample taken and current dse If there is n ZTAS curier, use the Magna freepst packs and pst t Magna Labratries fr Suth Essex r current service prvider in Nrth Essex, Beds and Lutn (cntact pharmacy) Medicatin Supply Tablets will nly be dispensed by the pharmacy nce a satisfactry FBC result has been received. Under n circumstances shuld there be a break in treatment except fr reasns f a red result r under specific medical advice. Every effrt must be made t ensure a bld result is btained befre a patient s treatment becmes prhibited Treatment breaks A treatment break, whether deliberate patient chice, gastric upset, r medically advised (e.g. surgery) is nt clinically significant if less than 48 hurs duratin, and treatment can cntinue as befre with the dse unchanged. A break f greater than 48 hurs is clinically significant in that the patient is at risk f prfund hyptensin if treatment resumes at full dse. Such a break shuld be fllwed by an increasing dsage titratin whereby the patient receives 12.5mg n day 1, and has returned t their riginal dse after 7 t 10 days. The mnitring frequency may als change depending n the duratin f the break. The mental health pharmacist and cnsultant must be infrmed f any break that is greater than 48 hurs s that advice can be given and the recrds held by ZTAS/DMS/CPMS can be updated. Re-titratin shuld ccur in an inpatient envirnment Admitting a Patient n Clzapine Befre any clzapine is prescribed r administered, the pharmacy must be infrmed when any clzapine patient is admitted r transferred frm anther unit.

13 The pharmacist will then check that the patient is currently registered fr clzapine treatment, they have a valid bld result and that n treatment break has ccurred. The recrds held by ZTAS/DMS/CPMS will als be updated. Clzapine must nt be prescribed r administered until it is cnfirmed that the bld result is current and that n treatment break has ccurred. If the patient is admitted ut f pharmacy hurs, the dctr, cmmunity team r n-call pharmacist may help t cnfirm these details Discharging a Patient n Clzapine The amunt f clzapine supplied n a discharge nte must crrespnd t the patient s mnitring frequency as the pharmacy can nly supply medicatin fr the duratin f the current valid bld result. The dctr must infrm the mental health pharmacist and cmmunity Care-Crdinatr when any clzapine patient is discharged s that an utpatient prescriptin can be written and the patient s cntact details can be updated. Arrangements must als be made with the patient, cmmunity team and pharmacy regarding future bld tests and medicatin supply. The supply may als ccur using the clzapine hme delivery service if lcal agreements are in place. Please cntact pharmacy fr further infrmatin befre changing any existing arrangements Transferring a Patient n Clzapine t anther Unit The dctr must infrm the mental health pharmacist when any clzapine patient is transferred t anther unit s that a cntinuus supply f medicatin can be arranged and the recrds held by ZTAS/DMS/CPMS can be updated. In Nrth Essex, the clzapine clinic shuld be infrmed Transferring a Clzapine Patient t anther Cnsultant If a clzapine patient is transferred t the care f a different cnsultant, the new cnsultant shuld infrm the mental health pharmacist r clzapine clinic in the Nrth as sn as pssible s the recrds held by ZTAS/DMS/CPMS can be updated. This is essential s that any alerts sent by ZTAS/DMS/CPMS are sent t the crrect cnsultant Discntinuing Clzapine Treatment In the event that clzapine treatment is t be discntinued, the dctr must infrm the mental health pharmacist r clzapine clinic in the Nrth. The pharmacist r clinic nurse will cancel the patient s clzapine prescriptin (if an utpatient) and cntact ZTAS/DMS/CPMS t change the patient s treatment status t discntinued. The patient must cntinue t have bld tests at their regular mnitring interval fr fur weeks after they stp taking clzapine. This shuld be undertaken by the member f the cmmunity team if using the hme delivery system Outpatient Prescriptins Outpatient prescriptins fr Suth Essex patients are held in pharmacy and dispensed frm fr three mnths, at which time they are rewritten and sent t the registered cnsultant fr signing. The clzapine hme delivery service may als be available.

14 Fr Nrth Essex patients, utpatient prescriptins are held by the clzapine clinic and a faxed cpy f the riginal is held in the dispensary fr 6 dispensing episdes. After this time, a new prescriptin is requested frm the clzapine clinic Making Dses Changes in Outpatient Clinics In Suth Essex, when a clzapine dse r dse time is changed in the cmmunity, the mental health pharmacist must be infrmed s the prescriptin held in the pharmacy can be amended accrdingly. This is the respnsibility f the prescriber making the change. If using the hme delivery service then the requisite service shuld be cntacted. In Nrth Essex, dse changes require a new prescriptin t be written and scanned/faxed t the Pharmacy at Chelfrd Curt Cllectin f Clzapine Tablets frm Cmmunity Teams Clzapine is regularly dispensed and sent t cmmunity teams (e.g. Grays Hall, Taylr Centre) fr cllectin. If medicatin is nt cllected within ne week f dispensing, the mental health pharmacist r supplying dispensary must be infrmed. Any medicatin that is given t a patient after this time may result in a supply f clzapine in excess f that permitted by the bld result. The date f dispensing is printed n all pharmacy labels and cmmunity teams shuld keep a recrd f all medicatin it receives, including the date f dispensing and the date f cllectin Smking Hydrcarbns cntained in cigarette smke induce CYP1A2, the main enzyme respnsible fr clzapine metablism. Smking can reduce clzapine plasma levels by as much as 70%. If smene taking clzapine stps smking, it is expected that their plasma clzapine level will increase dramatically, pssibly resulting in txicity. The use f nictine replacement therapy has n effect n enzyme activity, s the effect n plasma clzapine levels will be the same as in a patient wh is nt prescribed NRT. It takes apprximately five t seven days fr the enzymes t adjust t the change in smking habits. When a clzapine patient stps smking, either by chice r n admissin t a smke-free ward, a clzapine assay shuld be cnducted as sn as pssible. Due t the pssibility that the patient may nt have been fully cmpliant prir t admissin, this test shuld then be repeated seven days later. These results, tgether with any previus assay results, shuld then be used t determine the desired plasma level fr the individual patient. Dses shuld then be adjusted and assays shuld be repeated regularly until the plasma clzapine level has stabilised at the desired level. Please cntact pharmacy fr advice Inpatient initiatin f clzapine Inpatients with treatment resistant schizphrenia may be cnsidered fr clzapine initiatin if certain criteria are fulfilled:-

15 Clzapine treatment will be initiated by a cnsultant psychiatrist with the agreement f the inpatient ward. Baseline investigatins and registratin shuld be undertaken prir t admittance when pssible. (see Appendix 5) Only patients likely t be adherent with ral medicatin shuld be cnsidered. The patient must understand the need fr, and agree t underg regular bld tests and daily physical mnitring during the early dse-titratin phase. Baseline bld test results and ECG must be within nrmal limits befre clzapine is started (specialist examinatin is recmmended if there are cardiac abnrmalities r a histry f heart disease. Clzapine is cntraindicated in patients with severe cardiac disrders). Many adverse effects f clzapine are dse-dependent and assciated with the speed f titratin. T minimise these prblems it is imprtant t start at a lw dse and increase slwly (see Appendices 3a and 3b). Cnsultant s Checklist: 1. Discuss with patient/family/carers:- Realistic expectatins f treatment including time frames Hw t recgnise adverse reactins and side effects f clzapine (tiredness; dizziness; pstural hyptensin; hypersalivatin; raised temperature/cugh/signs f infectin; tachycardia; fitting) What t d if adverse events ccur Smking and clzapine interactin 2. Patient t give infrmed cnsent 3. Full medical histry review 4. Full medicatin review cautin in patients taking sedatives r benzdiazepines, antichlinergics, antihypertensives, alchl. Bne-marrw suppressants (e.g. Carbamazepine, dept antipsychtics) shuld be withdrawn befre starting clzapine 5. Full physical examinatin 6. Perfrm baseline tests (see Appendix 5) 7. Ask pharmacy t register patient (Suth Essex) r register patient directly (Nrth Essex) clzapine may nly be started nce the patient has been registered and has a valid bld result taken in the last 10 days 8. Patient will be reviewed medically nce a week as a minimum during the first 4 weeks f treatment Dsing

16 Usually the dse titratin shuld be accrding t the suggested guidelines fr inpatient initiatin (see Appendix 3a and 3b). Reasns fr variatin frm this regimen shuld be dcumented in the medical ntes Clzapine levels are lwer in males, smkers and yunger adults. Switching frm ther antipsychtics The switching regimen will be largely dependent n the patient s mental state. Cnsider additive side-effects f the antipsychtics (e.g. effect n QTc) Cnsider drug interactins (e.g. risperidne may increase clzapine levels). All depts shuld be stpped befre clzapine is started. Risperdal Cnsta shuld be stpped several weeks befre starting clzapine. This wuld nrmally be 3 4 weeks. Other antipsychtics and clzapine may be crss-tapered with varying degrees f cautin. Suggested titratin regimen clzapine inpatients See Appendix 3 Clzapine Initiatin Prescriptin Charts. Mnitring by the ward in the early dse-titratin phase (see Appendix 3c). Bld pressure (BP), temperature and pulse. After the first dse, mnitr BP, temperature and pulse 1-3 hurs afterwards. (This may nt be necessary if the first dse is given at bedtime.) Thereafter, the patient shuld be seen at least nce a day, and all three parameters shuld be mnitred befre and after the mrning dse. Appendix 4 shuld be used fr recrd keeping. Standing and supine BP shuld be mnitred daily fr three weeks fr patients with Parkinsn s Disease. Cntinue daily mnitring fr 2 weeks and at least until there are n unacceptable adverse effects. Alternate day mnitring may then be undertaken until a stable dse is reached. Thereafter mnitr at time f bld testing. Side effects shuld be mnitred and dcumented after every dse Weight, lipids, plasma glucse, LFTs and cardiac functin shuld be mnitred at baseline and then regularly thrughut treatment. (appendix 4) The ward shuld infrm the prescriber (r duty dctr ut f hurs):- If temperature rises abve 38 0 C (this is very cmmn and is nt a gd reasn, n its wn, fr stpping clzapine) If pulse is >100 bpm (als cmmn but may rarely be linked t mycarditis)

17 If BP Pstural drp f > 30 mmhg (systlic). If necessary measure bld pressure standing and sitting. If patient is clearly ver-sedated If any ther adverse effect is intlerable. Additinal mnitring requirements after the first mnth (see Appendix 5) Where available, cnsider als use f ECG (benefit nt established). Adverse effects Sedatin and rthstatic hyptensin (with r withut syncpe) are cmmn at the start f treatment. These effects can usually be managed by reducing the dse r slwing dwn the rate f titratin. Many ther adverse effects assciated with clzapine can als be managed by dse reductin. Patients may experience ECG changes, including ST depressin, flattening f T waves, which nrmalise after discntinuatin f Clzapine. The clinical significance is unclear but may be related t mycarditis. Islated cases f cardiac arrhythmias, pericarditis/pericardial effusin and mycarditis have been reprted, sme f which have been fatal. Mycarditis has usually ccurred in the first tw weeks f treatment, whereas cardimypathy has tended t be later. Patients, wh have persistent tachycardia at rest, especially during the first 2 mnths f treatment, shuld be clsely bserved fr ther signs r symptms f mycarditis r cardimypathy. These include shrtness f breath, palpitatins, arrhythmia, symptms mimicking mycardial infarctin, chest pains and ther unexplained symptms f heart failure (unexplained fatigue, dyspnea, tachypnea). Flu-like symptms may als ccur. Esinphilia may accmpany mycarditis and pericarditis/pericardial effusin. In patients with suspected clzapine-induced mycarditis r cardimypathy, the drug must be stpped and the patient referred t a cardilgist. If clzapine-induced mycarditis r cardimypathy is cnfirmed, the patient must nt be re-expsed t clzapine Clzapine re-challenge Infrmatin pertaining t the re-intrductin f clzapine after a red result can be fund in Appendix Cmmunity Clzapine Initiatin (Nrth Essex) In Nrth Essex, clzapine may als be initiated in the cmmunity setting either in the patient s wn hme r a day care setting. The patient shuld be registered with CPMS and have all baseline assessments cmpleted as fr inpatient initiatin abve.

18 Cmmunity initiatin requires a slwer, flexible titratin schedule. An example dsing schedule can be fund in The Maudsley Prescribing Guidelines in Psychiatry. This r anther titratin schedule shuld be used and prescribed n the cmmunity initiatin chart (Appendix 3c). The clzapine clinic nurse shuld be the lead n the practicalities f cmmunity initiatin. Once the decisin t use cmmunity initiatin has been made, a cpy f the cmmunity initiatin chart shuld be scanned r faxed t the dispensary at Chelfrd Curt. A supply will be made fr each day up t the validity f the prescriptin. This shuld be taken t the patient each day and signed fr n the cmmunity initiatin chart t prvide an audit trail. This includes medicatin left with the patient fr evening dses. Arrangements fr mnitring must be made and agreed with the patient prir t initiatin f clzapine. Bld mnitring is required as fr inpatient initiatin. Observatin mnitring is suggested as fllws: Day 1 pulse, temperature and lying/standing bld pressure pre-dse then hurly fr 6 hurs pst-dse Day 2 pulse, temperature and lying/standing bld pressure pre-dse then 2 and 6 hurs pst-dse Day 3 pulse, temperature and lying/standing bld pressure pre-dse then 6 hurs pst-dse. FBC t be taken. Days 4-14 pulse, temperature and lying/standing bld pressure at least nce a day. FBC t be taken n day 10. Adverse effect mnitring shuld ccur at least weekly with the prescriber infrmed if any effects r bservatins are nted as abve. The patient shuld be seen by a dctr at least weekly during initiatin. After tw weeks, patients shuld be assessed fr their need t cntinue n initiatin r be transferred t the utpatient clzapine clinic n a regular dse. 2.7 Risperidne Lng-Acting Injectin (RISPERDAL CONSTA ) Indicatins Risperidne lng acting injectin (RLAI) is indicated fr the maintenance treatment f schizphrenia in patients currently stabilised with ral antipsychtics. It is nt indicated fr treatment resistant schizphrenia. RLAI shuld nt be prescribed fr patients wh have shwn little r n respnse t ral risperidne. Fr further infrmatin relating t patient selectin and inclusin criteria fr the use f RLAI please see Appendix 7 (guidelines fr the use f Risperidne lng acting injectin) Treatment As it is nt pssible t give a test dse f RLAI, patients must be prescribed ral risperidne fr several days befre RLAI is initiated t assess tlerability (that is, t rule ut hyptensin r EPSE (extra-pyramidal side-effects)). The starting dse shuld nrmally be 25mg, althugh if a patient is taking mre than 4mg per day f

19 ral risperidne, RLAI may be started at 37.5mg. RLAI is t be administered frtnightly. Oral risperidne (r ther current ral antipsychtic) must be cntinued at the same dse fr at least fur t six weeks fllwing the first injectin, and then tapered ff ver the next tw weeks. RLAI releases nly small amunts f drug during the first three weeks. The main release starts in week fur and peaks in weeks five t six.) Further supplementatin f RLAI with ral antipsychtics shuld nly ccur in exceptinal circumstances and must be kept under clse review. The dse f RLAI shuld nt be increased fr at least six (t eight) weeks as steady state will nt have been reached and therefre assessment f respnse will nt be pssible. At this pint, it may be increased by 12.5mg (if cnsidering abve 50mg, 62.5mg can be achieved by using 25mg and 37.5mg injectins) and a further six t eight weeks shuld elapse befre any further increase. RLAI may nly be initiated by Cnsultants. Other grades may nt initiate therapy r adjust dses withut direct instructin frm their cnsultant. If there is n significant imprvement after six mnths f treatment with RLAI, cnsideratin shuld be given t withdrawing it. Prir t cmmencing cnsultants are reminded that befre cmmencing RLAI an initiatin frm (Appendix 7) needs t be cmpleted and frwarded t pharmacy Discntinuatin When discntinuing RLAI, the plasma level due t the last injectin will nt have declined significantly until 7-8 weeks after its administratin. This must be cnsidered when starting a new medicatin and is especially relevant if initiating clzapine Strage RLAI packs must be refrigerated at 2-8C. Strage at 8-25C reduces the shelf life t 7 days. Packs must nt be expsed t temperatures in excess f 25C. After recnstitutin, RLAI shuld be administered immediately. If nt used immediately, it is cnsidered suitable fr use fr a maximum f 6 hurs, if stred belw 25C Recnstitutin f high dse RLAI Instead f giving tw injectins r a large vlume injectin each time a dse is due, the fllwing prcedure may be fllwed, althugh this is als utside the license:- 1. Make up ne 37.5mg injectin, and draw it up in the syringe. 2. Use this slutin t make up the 2nd 37.5mg injectin, and then draw it all up int the syringe. (25mg & 50mg injectins culd be used t achieve the 75mg injectin and 25mg & 37.5mg injectins culd be used t achieve 62.5mg.) 3. Yu nw have a syringe cntaining 75mg (r 62.5mg) in a little mre than 2mls. 4. Give the injectin in the usual way.

20 If yu have any dubts r questins abut this, please cntact pharmacy. Patient Status Cmpliant with ral risperidne. N previus histry f treatment with risperidne. Dcumented previus histry f treatment with risperidne. Well tlerated. Patient currently prescribed ral risperidne but nn-cmpliant. Patient currently prescribed anther ral atypical antipsychtic but nncmpliant. Patient currently prescribed dept typical antipsychtic. Elderly (ver 65 years) Actin Cntinue with ral risperidne. Assess tlerability by prescribing ral risperidne fr several days at a dse f at least 2mg daily. Cnsider RLAI 25mg every 2 weeks (if effective ral dse is less than r equal t 4 mg daily). If current ral dse is 4mg per day r less, cnsider RLAI 25mg every 2 weeks. If current ral dse is abve 4mg per day, cnsider RLAI 37.5mg every 2 weeks. Assess tlerability by prescribing ral risperidne fr several days at a dse f at least 2mg daily. Cnsider RLAI 25mg every 2 weeks. Assess tlerability by prescribing ral risperidne fr several days at a dse f at least 2mg daily. Cnsider RLAI 25mg every 2 weeks. Administer first dse ne week befre dept is due and give last dse f typical dept n the due date. The licensed dse is 25mg every 2 weeks fr ral dses less than r equal t 4 mg daily. Fr dses in excess f 4 mg daily, administratin f RLA I 37.5 mg shuld be cnsidered. 2.8 Paliperidne Lng-Acting Injectin (XEPLION ) Indicatins Paliperidne LAI (PLAI) is indicated fr maintenance treatment f schizphrenia in adult patients stabilised with paliperidne r risperidne. (Oral paliperidne remains nn-frmulary) In selected adult patients with schizphrenia and previus respnsiveness t ral paliperidne r risperidne, PLAI may be used withut prir stabilisatin with ral treatment if psychtic symptms are mild t mderate and a lng-acting injectable treatment is needed. Fr further infrmatin relating t patient selectin and inclusin criteria fr the use f PLAI please see Appendix Treatment As it is nt pssible t give a test dse f PLAI, patients must be prescribed ral risperidne fr several days befre PLAI is initiated t assess tlerability (that is, t rule ut hyptensin r EPSE (extra-pyramidal side-effects)). The starting dse shuld nrmally be 150mg n day 1, 100mg n day 8 fllwed by a maintenance dse f 75mg ne mnth after day 8. PLAI is t be administered mnthly. If there is n significant imprvement after six mnths f treatment with PLAI, cnsideratin shuld be given t withdrawing it. Prir t cmmencing cnsultants are reminded that befre cmmencing RLAI an initiatin frm (Appendix 7) needs t be cmpleted and frwarded t pharmacy.

21 2.8.3 Discntinuatin When discntinuing PLAI, the plasma level due t the last injectin will nt have declined significantly until several weeks after its administratin. This must be cnsidered when starting a new medicatin and is especially relevant if initiating clzapine Strage PLAI packs must be kept at rm temperature and nt refrigerated. Packs must nt be expsed t temperatures in excess f 30C 6. If yu have any dubts r questins abut this, please cntact pharmacy. Patient Status Cmpliant with ral risperidne. N previus histry f treatment with risperidne. Dcumented previus histry f treatment with risperidne. Well tlerated. Patient currently prescribed ral risperidne but nn-cmpliant. Patient currently prescribed anther ral atypical antipsychtic but nncmpliant. Patient currently prescribed dept typical antipsychtic. Elderly (ver 65 years) Actin Cntinue with ral risperidne. Assess tlerability by prescribing ral risperidne fr several days at a dse f at least 2mg daily. Cnsider PLAI 150mg n day 1, 100mg n day 8 and maintenance dse 75mg ne mnth later. Maintenance dses t be given every mnth Cnsider PLAI 150mg n day 1, 100mg n day 8 and maintenance dse 75mg ne mnth later. Maintenance dses t be given every mnth Assess tlerability by prescribing ral risperidne fr several days at a dse f at least 2mg daily. Cnsider PLAI 75mg nce a mnth Assess tlerability by prescribing ral risperidne fr several days at a dse f at least 2mg daily. Cnsider PLAI 75mg nce a mnth Efficacy and safety in elderly > 65 years have nt been established. 2.9 Aripiprazle Lng-Acting Injectin (ABILIFY MAINTENA ) Indicatins Aripiprazle lng acting injectin (ALAI) is indicated fr the maintenance treatment f schizphrenia in patients currently stabilised with ral antipsychtics. It is nt indicated fr treatment resistant schizphrenia. ALAI shuld nt be prescribed fr patients wh have shwn little r n respnse t ral aripiprazle. Fr further infrmatin relating t patient selectin and inclusin criteria fr the use f LAI please see Appendix 7 (guidelines fr the use f Aripiprazle lng acting injectin) Treatment As it is nt pssible t give a test dse f ALAI, patients must be prescribed ral aripiprazle fr several days befre ALAI is initiated t assess tlerability (that is, t rule ut adverse drug reactin r EPSE (extra-pyramidal side-effects)). ALAI is t be administered mnthly n the same date f each mnth. Please nte this is nt every 28 days. T prvide flexibility in administratin, fr example at weekends, the interval between injectins can be 26 days but n less. Oral aripiprazle must be cntinued at the same dse fr 14 days at a dse f 10 20mg daily fllwing the first injectin. ALAI releases nly small amunts f drug

22 during the first few weeks and requires supplementatin during this initial perid. The main release starts after the initial tw week perid. The starting dse f ALAI is 400mg nce a mnth. This may be reduced, shuld side effects be prblematic, t 300mg nce a mnth. The dse cannt be increased further than 400mg nce a mnth as there is n evidence t suggest efficacy. ALAI is nt recmmended fr thse ver 65 years f age. If there is n significant imprvement after six mnths f treatment with ALAI, cnsideratin shuld be given t withdrawing it. Cnsultants are reminded that befre cmmencing a LAI, an initiatin frm (Appendix 7) needs t be cmpleted and frwarded t pharmacy Discntinuatin When discntinuing ALAI, the plasma level due t the last injectin will nt have declined significantly until 7-8 weeks after its administratin. The terminal eliminatin half-life f a 400mg Maintena dse is 45 days 6. This must be cnsidered when starting new medicatin and is especially relevant if initiating clzapine Strage ALAI packs must be kept at rm temperature and nt refrigerated. Packs must nt be expsed t temperatures in excess f 25C. After recnstitutin, ALAI shuld be administered immediately. If nt used immediately, it is cnsidered suitable fr use fr a maximum f 4 hurs, if stred belw 25C 6. If yu have any dubts r questins abut this, please cntact pharmacy. Patient Status Cmpliant with ral ariprazle. N previus histry f treatment with aripiprazle. Dcumented previus histry f treatment with aripirazle. Well tlerated. Patient currently prescribed ral aripiprazle but nn-cmpliant. Patient currently prescribed anther ral atypical antipsychtic but nncmpliant. Elderly (ver 65 years) Actin Cntinue with ral aripirazle. Assess tlerability by prescribing ral aripirazle fr several days at a dse f at least 10mg daily. Cnsider ALAI 400mg nce a mnth. Cnsider ALAI 400mg nce a mnth. Assess tlerability by prescribing ral aripiprazle fr several days at a dse f at least 10mg daily. Cnsider ALAI 400mg nce a mnth. Aripiprazle LAI is nt recmmend fr thse ver 65 years f age Dse adjustments f Abilify Maintena in patients wh are taking cncmitant strng CYP2D6 inhibitrs, strng CYP3A4 inhibitrs, and/r CYP3A4 inducers fr mre than 14 days 6 Patients taking 400 mg f Abilify Maintena Strng CYP2D6 r strng CYP3A4 inhibitrs Strng CYP2D6 and strng CYP3A4 inhibitrs Adjusted dse 300 mg 200 mg

23 CYP3A4 inducers Patients taking 300 mg f Abilify Maintena Strng CYP2D6 r strng CYP3A4 inhibitrs Strng CYP2D6 and strng CYP3A4 inhibitrs CYP3A4 inducers Adjusted dse Avid use 200 mg 160 mg Avid use 2.10 Olanzapine Lng Acting Injectin (Zypadhera ) Olanzapine LAI remains nn-frmulary. When a nn-frmulary applicatin fr prescribing is made t the chair f the Medicines Management Grup an utline f plans fr immediate and lng-term mnitring must be included. There shuld als be cnfirmatin that the patient has agreed t the stringent mnitring fllwing each dse. References 1. Cnsensus statement n high-dse antipsychtic medicatin May 2014 Ryal Cllege f Psychiatrists 2. BNF n-line, current editin, Accessed May NICE CG178, March Psychsis and schizphrenia in adults: preventin and management Clinical guideline [CG178] 4. Suth Lndn & Maudsley NHS Fundatin Trust Prescribing Guidelines 12 th editin, Wiley Blackwell, Psychtrpic Drug Directry 2016, Bazire S., Page Brthers Ltd 6. Summary f Prduct Characteristics, varius, Accessed May Shared care in mental health, Oxfrd handbks, ISBN NICE CG 120. March Psychsis with cexisting substance misuse: Assessment and management in adults and yung peple 9. NICE CG 178. February Psychsis and schizphrenia in adults: treatment and management. 10. Nice QS 88 June 2015 Persnality Disrders: Brderline and Antiscial Persnality disrders: brderline and antiscial Intrductin Guidance and guidelines NICE

24 Physical Health Mnitring f Adults (Children and Adlescents) taking Antipsychtics (except clzapine) Appendix 1 Name: D.O.B: NHS number: Ward: Parameter Baseline 1 mnth 3 mnths 6 mnths 9 mnths 12 mnths Then Date Weight (BMI & waist size) Annually LFTs Annually Fasting plasma glucse 6 mnthly fr lanzapine, annually fr all thers U&Es Annually Fasting bld lipids Annually FBC Annually TFTs Annually Prlactin Annually BP/pulse Befre starting antipsychtic medicatin & during significant dse changes, see SPC f individual drug fr full guidance Annually ECG Blank (un-shaded) bxes indicate mnitring required Recmmended pre-treatment and at dse increase fr typical antipsychtics, high dse treatment (>BNF maximum) and cmbinatin treatment with mre than ne antipsychtic Annually Physical health mnitring f thse taking antipsychtic drugs shuld be based n the schedule abve in additin t any specific SPC/NICE requirements. Mre frequent mnitring shuld be cnducted if there are clinical symptms r changes detected are apprpriately actins taken/cascaded Perfrm a full physical examinatin befre starting antipsychtic therapy. Recrd BP and pulse and, befre starting antipsychtic medicatin, ffer all in-patient service users with schizphrenia (and related disrders) an electrcardigram (ECG). References 1. Suth Lndn & Maudsley NHS Fundatin Trust Prescribing Guidelines 12 th editin, Infrma Healthcare, 2010

25 HIGH DOSE AND COMBINATION ANTIPSYCHOTIC TREATMENT MONITORING FORM Appendix 2 Patient s name: NHS Number Cnsultant Date f Birth: Ward: Date This frm is t be cmpleted prir t cmmencing antipsychtic drugs that either exceed 100% f the BNF maximum recmmended dse (including PRN) OR invlve mre than ne antipsychtic drug prescribed n a regular basis HIGH DOSE OR COMBINATION ANTIPSYCHOTIC TREATMENT SHOULD BE REVIEWED AT INTERVALS OF TWO WEEKS OR LESS AND DISCONTINUED IF NO ADDITIONAL CLINICAL BENEFIT IS OBSERVED. Current Medicatin Drug name and frmulatin Current ttal daily dse Planned maximum daily dse Previus Antipsychtic Medicatin Drug name and frmulatin Ttal daily dse Reasn fr stpping Reasns fr High Dse / Cmbinatin Antipsychtics

26 YES NO 1. Has this patient been prescribed clzapine? If NO, please state reasn(s) fr nt prescribing If YES, please state reasn(s) fr discntinuatin 2. Has the patient shwn signs f adverse effects t antipsychtic drugs r is there evidence f drug interactins? If YES, please give details 3. Is the patient subject t Sectin 58 (cnsent t treatment) requirements? If YES, has the patient either given infrmed cnsent t high dse treatment and T2 been amended accrdingly, r SOAD cnsent has been btained n Frm T3? (Answer must be YES) Mnitring required prir t cmmencing high dse treatment Date ECG FBC U&Es LFTs TFTs Glucse Lipids Nrmal / Abnrmal Mnitring required after cmmencing high dse treatment (repeated at a minimum f every three mnths) Date ECG (Nrm/Abn) FBC (Nrm/Abn) U&Es (Nrm/Abn) LFTs (Nrm/Abn) TFTs (Nrm/Abn) Glucse (Nrm/Abn) Lipids (Nrm/Abn) Cnsultant Name: Signature: Date f cmmencing High Dse Treatment:

27 Appendix 3a (Suth) Clzapine Initiatin Chart (page1) Frename Surname Date f Birth NHS N. Affix Addressgraph Label Here Cnsultant Ward/Unit Date Chart Started Date Chart Finished Clzapine PIN Ntes 1. This chart shuld nly be used fr patients starting treatment with clzapine. 2. Attach this chart t the main prescriptin chart, which must be endrsed Clzapine as per Clzapine Initiatin Chart in ne f the prescriptin bxes in the regular medicatin sectin. 3. The CONSULTANT shuld sign this chart fr the start f week 1. Subsequent prescriptins may be signed by any apprpriate prescriber. 4. The nurse administering the clzapine shuld sign in the Given By bx beside each dse. 5. Once the maintenance dse has been reached all unused bxes shuld be crssed ut and initialled by the prescriber. The maintenance dse f clzapine shuld then be prescribed n the main drug chart. MONITORING Physical mnitring shuld be dne accrding t the guidelines in the Trust s Frmulary and prescribing Guidelines and using the mnitring frms in Appendix 1 and Appendix 2. See Trust Intranet>Library>Medicines Management>Frmulary and Prescribing Guidelines>Sectin 2 Treatment f Psychsis >2.8 Guidelines fr the Use f Clzapine. Day Week 1 Ttal Daily Dse (mg) Cnsultant s signature... Date... Print Name... Tel/Bleep... Given By Date Mrning Dse (nurse sign) Evening Dse mg xxxxxxxx xxxxxxx Clzapine 12.5mg 2 25mg Clzapine 12.5mg Clzapine 12.5mg 3 50mg Clzapine 25mg Clzapine 25mg 4 50mg Clzapine 25mg Clzapine25mg 5 75mg Clzapine 25mg Clzapine 50mg 6 75mg Clzapine 25mg Clzapine 50mg 7 100mg Clzapine 50mg Clzapine 50mg Pharmacy Week 1 17x25mg Screened by... Date... Dispensed by... Date... Given By (nurse sign) Checked by... Date... BLOOD TESTS Pre-treatment sample: Date sample taken... Green result cnfirmed ; Date... Signature... Date Clzapine started:...(must be within 10 days f pre-treatment sample) Secnd bld sample: (must be taken within 7 days f the pre-treatment sample) Secnd sample shuld be taken by (date)...

28 Clzapine Initiatin Chart (page2) Frename NHS N. Surname Ward/Unit Week 2 Prescriber s signature... Date... Print Name... Tel/Bleep... Day Ttal Daily Given By Given By Dse (mg) Date Mrning Dse (nurse sign) Evening Dse (nurse sign) 8 125mg Clzapine 50mg Clzapine 75mg 9 150mg Clzapine 75mg Clzapine 75mg mg Clzapine 75mg Clzapine 100mg mg Clzapine 100mg Clzapine 100mg mg Clzapine 100mg Clzapine 125mg mg Clzapine 125mg Clzapine 125mg mg Clzapine 125mg Clzapine 150mg Pharmacy Week 2 20x25mg 9x100mg Screened by... Date... Dispensed by... Date... Checked by... Date... BLOOD TESTS Third bld sample: Date sample shuld be taken:... (7 days after secnd bld sample) Date sample taken... Green result cnfirmed ; Date... Signature... Week 3 nwards: Prescribe clzapine n the main drug chart. NB. Crss ut unused prescriptin bxes n this drug chart.

29 Inpatient Clzapine Initiatin Prescriptin Chart Appendix 3b (Nrth) Frename DOB Ward Surname NHS Number Cnsultant Ntes: 1. This chart is fr inpatient clzapine initiatin nly and shuld be attached t the inpatient Prescriptin and Medicines Administratin Chart (PMAC) 2. Ensure clzapine is written n the regular medicatin sectin f the PMAC with reference t this initiatin chart as fllws see clzapine initiatin chart 3. The prescriptin fr the first week shuld be signed by the cnsultant. Thereafter, prescriptins can be signed by an apprpriate prescriber 4. Titratins shuld start n a Mnday, with prescriptins and supply rganised the previus week 5. Administratin shuld be signed by the registered nurse in the given by bx next t the dse 6. Once the target maintenance dse is reached, clzapine shuld be prescribed n the inpatient PMAC as a regular medicine and any remaining prescriptins crssed ff this chart 7. Ensure pre-treatment baseline assessment is cmpleted as per Appendix 5Clzapine can nly be given t patients registered with CPMS and with a green bld result. Please dcument CPMS number and date f 1 st green result belw t cnfirm. CPMS Number Date f 1 st green result Mnitring: Cmplete the fllwing n a track and trigger frm and recrd n Paris (Remedy): Day Mnitring 1 Pulse, temperature and bld pressure pre-dse and hurly fr 6 hurs pst-dse 2 Pulse, temperature and bld pressure pre-dse, 2 and 6 hurs pst-dse 3 Pulse, temperature and bld pressure pre-dse and 6 hurs pst-dse. FBC t be taken 4 Pulse, temperature and bld pressure pre-dse and 6 hurs pst-dse. 5 Pulse, temperature and bld pressure pre-dse and 6 hurs pst-dse Pulse, temperature and bld pressure pre-dse and 6 hurs pst-dse. FBC t be taken n day 10 FBC (t include differential white cell cunt): Week Frequency Validity (if green) 1-18 Weekly 10 days Frtnightly 21 days 53 nwards Mnthly 42 days

30 Frename DOB Ward Surname NHS Number Cnsultant Week 1 CLOZAPINE Pharmacy Screened by: Ordered by: Quantity = 17 x 25mg (Half 25mg tablet fr 12.5mg dse) Cnsultant signature Print name Date Day Date 0900 Given by 1800 Given by mg X X mg 12.5mg 3 25mg 25mg 4 25mg 25mg 5 25mg 50mg 6 25mg 50mg 7 50mg 50mg Week 2 CLOZAPINE Pharmacy Screened by: Ordered by: Quantity: 20 x 25mg 9 x 100mg Prescriber signature Print name Date Day Date 0900 Given by 1800 Given by 8 50mg 75mg 9 75mg 75mg 10 75mg 100mg mg 100mg mg 125mg mg 125mg mg 150mg Week 3 CLOZAPINE Pharmacy Screened by: Ordered by: Quantity: 18 x 25mg 19 x 100mg Prescriber signature Print name Date Day Date 0900 Given by 1800 Given by mg 150mg mg 150mg mg 150mg mg 200mg mg 200mg mg 200mg mg 200mg NOW TRANSFER TO REGULAR MEDICINES ON INPATIENTDRUG CHART

31 Clzapine Cmmunity Initiatin Prescriptin Chart Appendix 3c Frename DOB Cnsultant Surname NHS Number Ntes: 1. This chart is fr cmmunity initiatin f clzapine nly 2. The prescriptin fr the first week shuld be signed by the cnsultant. Thereafter, prescriptins can be signed by an apprpriate prescriber 3. Titratins shuld start n a Mnday, with prescriptins and supply rganised the previus week 4. Administratin/supply shuld be signed by the registered nurse in the given by bx next t the dse 5. Once the target maintenance dse is reached, clzapine shuld be prescribed n an utpatient clzapine prescriptin 6. Ensure pre-treatment baseline assessment is cmpleted 7. Clzapine can nly be given t patients registered with CPMS and with a green bld result. Please dcument CPMS number and date f 1 st green result belw t cnfirm. CPMS Number Date f 1 st green result Mnitring: Cmplete the fllwing n a track and trigger frm and recrd n Paris (Remedy): Day Mnitring 1 Pulse, temperature and lying/standing bld pressure pre-dse and hurly fr 6 hurs pst-dse 2 Pulse, temperature and lying/standing bld pressure pre-dse, 2 and 6 hurs pstdse 3 Pulse, temperature and lying/standing bld pressure pre-dse and 6 hurs pstdse. FBC t be taken 4-14 Pulse, temperature and lying/standing bld pressure at least nce a day. FBC t be taken n day 10 FBC (t include differential white cell cunt): Week Frequency Validity (if green) 1-18 Weekly 10 days Frtnightly 21 days 53 nwards Mnthly 42 days

32 Frename DOB Cnsultant Surname NHS Number Week 1 CLOZAPINE Pharmacy Screened by: Ordered by: Supply received by: Cnsultant signature Print name Date Day Date 0900 Given by 1800 Given by Week 2 CLOZAPINE Pharmacy Screened by: Ordered by: Supply received by: Prescriber signature Print name Date Day Date 0900 Given by 1800 Given by Week 3 CLOZAPINE Pharmacy Screened by: Ordered by: Supply received by: Prescriber signature Print name Date Day Date 0900 Given by 1800 Given by NOW TRANSFER TO AN OUTPATIENT CLOZAPINE PRESCRIPTION

33 Appendix 4 Clzapine Inpatient Mnitring Recrd See sectin fr further infrmatin Name: D.O.B: NHS number: Ward: PHYSICAL: Date Time Cmpleted By Bld Pressure Pulse Temperature ( C) SIDE EFFECTS: Restlessness Blurred Visin Cnfusin Diarrhea Dry Muth Excessive Sweating Excessive Salivatin Muscle Spasm Nausea r Vmiting Sedatin Tremr Other KEY: 0= nne 1= minr 2= mderate 3=severe

34 Appendix 5 Clzapine Physical Mnitring Recrd (See sectin f EPUT frmulary fr further infrmatin) Name: D.O.B: NHS number: Ward: Baseline 1 mnth 3 mnths 6 mnths 12 mnths Onging Date Weight (BMI & waist size) Fasting lipid prfile Bld glucse randm/fasting Annually Annually Annually Liver functin Annually ECG Urea & Electrlytes Full bld cunt Prlactin Clzapine may cause cardimypathies and mycarditis. Check ECG when maintenance dse is reached. Check annually if high dse (>600mg daily) Annually As per clzapine prtcl. Weekly fr 18 weeks, then frtnightly fr up t 1 year, then 4-weekly. Additinal mnitring may be required if apprpriate Hyperprlactinaemia is rare with clzapine - check serum prlactin if symptms ccur (menstrual disturbance, galactrrhea, gynaecmastia, sexual dysfunctin). Cnsider ther pssible causes. BP and Pulse Daily during titratin See appendix 4 Blank (un-shaded) bxes indicate mnitring required Annually ECG cmment:- Ntes

35 Appendix 6 Clzapine re-challenge after a red bld result Prcedure fr clzapine re-challenge after a red bld result unlicensed use 1. Befre cnsidering clzapine re-challenge in a patient wh has had a red bld result, alternative drug treatments shuld be cnsidered. The Maudsley Prescribing Guidelines 12 th Editin cntains a table listing alternatives t clzapine fr refractry schizphrenia. 2. If these ptins have been tried withut success, r if they are nt cnsidered apprpriate, the pssibility f re-starting the patient n clzapine shuld be discussed within the clinical team and with senir clleagues. These discussins shuld take int accunt the patient s current mental status and their previus respnse t clzapine. 3. If there is agreement that re-challenge with clzapine is justified, the patient s cnsultant shuld discuss the case with the lcal cnsultant haematlgist. 4. If the haematlgist agrees that it is safe t prceed with a re-challenge, the patient s cnsultant shuld cntact the manufacturer f clzapine 5. The cmpany will issue a Patient Re-challenge Request frm which the cnsultant must cmplete and return 6. On receipt f this frm, the cmpany will issue the fllwing dcuments: A standard clzapine patient registratin frm A Patient Re-challenge Agreement frm A Off-label Treatment Agreement frm 7. These frms must be cmpleted by the cnsultant and returned befre the rechallenge can prceed. It is imprtant t nte that the Off-label Treatment Agreement is a disclaimer which states that the manufacturer des nt recmmend the prescribing f clzapine fr re-challenge and that the cnsultant accepts full clinical respnsibility fr the decisin t prceed with this. 8. Once a prpsed starting date fr the re-challenge has been agreed, the hspital Pharmacy (and, if necessary, the lcal haematlgist), shuld be ntified. In additin, the chair f the Medicines management cmmittee shuld be ntified 9. The ratinale fr prceeding with clzapine re-challenge, and the subsequent discussins with haematlgists and the manufacturer, shuld be fully dcumented in the patient s ntes. The patient and/r their representative(s) shuld be infrmed f the unlicensed nature f this treatment and its assciated risks, and this discussin shuld be recrded in the ntes. Infrmed cnsent shuld als be btained.

36 Appendix 7 1. Intrductin Guidelines fr the Use f Lng Acting Injectins (Risperdal Cnsta / Xeplin / Abilify Maintena ) Risperidne, Paliperidne and Aripiprazle are effective atypical antipsychtics used in the treatment f schizphrenia and are currently recmmended as first line atypical ral antipsychtics (paliperidne is nn-frmulary),due t their lwer acquisitin csts than thers in the class. Lng Acting Injectins (LAIs) are a slw release injectable frm f the same drug, the acquisitin cst f which is very high cmpared with ther dept antipsychtics. Patient Selectin Criteria Patients wh are unlikely t cnsistently take ral medicatin shuld be cnsidered fr a dept r lng-acting injectin. As nn-adherence with ral treatment is the main reasn fr switching t a dept it des nt necessarily fllw that a patient prescribed ral aripiprazle r risperidne shuld autmatically be switched t a the equivalent LAI. A first generatin antipsychtic dept injectin shuld be cnsidered befre Risperidne, Paliperidne r Aripiprazle LAI unless there are cntra-indicatins. Patients suffering side effects n cnventinal dept injectins despite dse reductin, where apprpriate, shuld be cnsidered fr these secnd generatin preparatins. Patients wh are respnding well and nt experiencing intlerable side effects f cnventinal dept injectins shuld nt be transferred t Risperidne, Paliperidne r Aripiprazle LAI. Patients wh have shwn little r n respnse t ral aripiprazle/risperidne shuld nt be transferred t Risperidne, Paliperidne r Aripiprazle LAI. Risperidne, Paliperidne r Aripiprazle LAI are nt indicated fr Treatment Resistant Schizphrenia such patients shuld always be cnsidered fr clzapine. Clinicians wishing t initiate Risperidne, Paliperidne r Aripiprazle LAI must cmplete the frm verleaf. 2. Initiatin Dses LAIs have a unique release prfile and it must be remembered that there is virtually n release f active ingredient fr the first few weeks fllwing administratin. It therefre fllws that there will be n respnse during this perid and alternative treatment e.g. ral risperidne/paliperidne/aripiprazle r alternative dept needs t be cntinued (see the Trust Frmulary and Prescribing Guidelines). Dse equivalence shuld be taken int accunt in determining the starting dse, therefre a patient wh has been stable n 6mg f risperidne may be started n a dse f 37.5mg RLAI prviding all ther criteria have been met. All ther patients shuld start n a dse f 25mg. Fr aripiprazle, the usual starting dse is 400mg. Fr paliperidne patients shuld be given 150mg n day 1,100mg n day 8 transferred t a maintenance dse f 75mg ne mnth after day 8.

37 INITIATION OF RISPERIDONE/PALIPERIDONE/ARIPIRAZOLE LONG ACTING INJECTION (LAI) (RISPERDAL CONSTA / XEPLION / ABILIFY MAINTENA ) This authrisatin frm needs t be cmpleted prir t initiating risperidne/paliperidne/aripiprazle lng acting injectins (as agreed by the Medicines Management Cmmittee in September 2017). A new frm is required fr each treatment episde. Incrrect r partially cmpleted frms alng with requests fr LAI withut the requisite frm will be referred back t the prescribing cnsultant and may cause unnecessary delay in drug supply. Patient s name: Date f Birth: NHS Number: Ward: Name f LAI t be initiated 1. Is the patient suffering frm treatment resistant schizphrenia? (treatment resistant schizphrenia is nt a licensed indicatin and clzapine shuld be cnsidered) 2. Has a first generatin antipsychtic (FGA) dept injectin been tried prir t cnsidering LAI? (nn-adherence with ral therapy is the main reasn fr switching t a dept injectin; it des nt necessarily fllw that a patient prescribed ral risperidne/aripiprazle shuld autmatically be switched t LAI) 3. Did the patient respnd well t FGA dept injectins? 4. Did the patient experience intlerable side effects despite dse reductin? (patients wh are respnding well and nt experiencing intlerable side effects f cnventinal dept injectins shuld nt be transferred t LAI) Please prvide details f yur reasns fr wishing t use LAI in this patient Y / N Y / N Y / N Y / N Cnsultant Name: Signature: Date: Cntact Tel: Return t Ward Pharmacist fr clinical ratificatin Pharmacist Name: Signature: Date:

38 Appendix 8 Switching frm Quetiapine XL t Quetiapine IR Advice fr Health Prfessinals The fllwing advice has been develped t aid clinicians switch patients frm quetiapine extended release (XL) t quetiapine immediate release (IR). Switching frm XL t IR is recmmended acrss the health ecnmy t maximize the cst savings available. Switching hwever, is NOT mandatry and clinicians are reminded t cnsider individual patient circumstances befre attempting a switch as remaining n quetiapine XL may be in the best clinical interests f sme patients. There is little published evidence t guide clinicians n the best methd f switching between quetiapine XL and quetiapine IR tablets. Any switch shuld be fully discussed with the individual patient and carer, cmbined with increased mnitring fr adverse events. In general a straight swap frm nce daily XL t twice daily IR is apprpriate 1 but may be assciated with a slightly higher risk f sedatin and pstural hyptensin fllwing the switch. If sedatin and pstural hyptensin are a cncern clinicians may wish t cnsider giving a larger dse in the evening (see table 1). Althugh ther pharmackinetic parameters are similar the peak plasma cncentratin differ; quetiapine XL = 5-6hurs vs. IR = 1 hur. Fr details cmparisn between Quetiapine XL vs. IR clinicians are encuraged t visit the relevant SPC Table1: Switching between quetiapine XL and IR. Suggested dsing changes Current daily Dse f XL frmulatin Fr thse wh are tlerating quetiapine well and d nt have cmpliance cncerns Dsing Optins (quetiapine IR) Fr thse wh are (r are at risk f) experiencing sedatin r pstural hyptensin fllwing the switch * Quetiapine XL 100mg OD Quetiapine 50mg BD Quetiapine 25mg OM, 75mg ON Quetiapine XL 200mg OD Quetiapine 100mg BD Quetiapine 50mg OM, 150mg ON Quetiapine XL 300mg OD Quetiapine 150mg BD Quetiapine 100mg OM, 200mg ON Quetiapine XL 400mg OD Quetiapine 200mg BD Quetiapine 150mg OM, 250mg ON Quetiapine XL 600mg OD Quetiapine 300mg BD Quetiapine 200mg OM, 400mg ON Quetiapine XL 800mg OD Quetiapine 400mg BD Quetiapine 300mg OM, 500mg ON *Thse at increased risk f experiencing sedatin r pstural hyptensin fllwing the switch t quetiapine IR may include: the elderly, thse with learning disabilities, adlescents, cncurrent cardiac medicatin, and/r cncurrent CNS depressants.

39 Table 2: Current licensed indicatins 2 (see current BNF fr mre infrmatin) Frmulatin Current manufacturer license Number f daily dses Quetiapine XL Quetiapine IR Schizphrenia including preventin. Mania r depressin in biplar disrder Preventin f relapse in biplar disrder Add n treatment (t an antidepressant) in majr depressive episdes. Schizphrenia including preventin Mania in biplar disrder Preventin f relapse in biplar disrder Once daily Twice daily Depressin in biplar disrder Once daily *Althugh unlicensed in schizphrenia as a nce daily preparatin there are 3 small, shrt term studies supprting quetiapine IR nce daily and this is ccasinally dne in practice 3,4,5 Please cntact pharmacy fr further infrmatin