Clozapine treatment guidance Prescribing: The initiation of clozapine in TEWV is restricted to consultant psychiatrists registered with the CPMS. ALERT: Clozapine titration can be safely done in the community Please note: always consider physical health state, patient adherence with oral medication and blood tests, ability to see patient every day during the early titration phase, support for patient to attend team base or with collection/delivery of medicines, team resources and client preference. If you have any concerns with regard to the above consider using a crisis bed or admit to an in-patient area. CLOZAPINE CLINICAL ALGORITHM Decision to commence clozapine BASELINE ASSESSMENT AND COMMUNITY SUPPORT SET UP TITRATION AND DAILY MONITORING WEEKS 1 & 2 TITRATION AND WEEKLY MONITORING WEEKS 3 & 4 WEEKLY MONITORING WEEKS 5-18 2 WEEKLY MONITORING WEEKS 18 51 MONTHLY MONITORING WEEK 52 ONWARDS Green result Satisfactory Action continue with routine tests Amber result WBC or neutrophils counts below accepted levels Action Repeat test twice a week until either red or green Red result WBC below 3000/mm³ and/or absolute neutrophils below 1500/mm³ Action Immediate cessation of therapy. Sample blood daily until patient recovered. No further prescribing allowed unless an error has occurred or consultant takes full responsibility Interactions: Note that interactions with the following may significantly affect clozapine levels and dose adjustments may be required (see BNF for more details): - Antibiotics; Carbamazepine; SSRIs; Phenytoin; Smoking IF AT ANY POINT DURING THE PATHWAY THE CLIENT HAS A RED BLOOD RESULT IMMEDIATELY DISCUSS WITH THE CLIENT S CONSULTANT AND CARE CO-ORDINATOR SEEK MEDICAL ADVICE IF:- Temperature is above 38 Pulse is above 100 bpm Systolic blood pressure drops more than 30mmHg Over sedation Intolerable side effects At each consultation remind client to report any signs of infection e.g. fever or sore throat. Check bloods if symptoms of infection reported.
Baseline assessment and community set up Decision to commence clozapine made by multidisciplinary team and patient Confirm consultant registered with CPMS Patient education session to explain blood monitoring arrangements and side effects. Patient information leaflets provided and informed consent obtained. Baseline assessments of side effects and baseline BPRS completed and recorded Baseline physical examination carried out BP Temperature Pulse Weight ECG Fasting blood glucose LFT s U&E Lipids & Prolactin Height Waist circumference Check physical health history particularly cardiac and GI history and document. (Constipation: Warning letter regarding clozapine and constipation ) Baseline blood test (WCC and differential count) sent to local haematology labs Patient baseline blood test result entered on the patient registration form, and patient registered with CPMS. Confirmation of GREEN baseline result from CPMS Prescribe initial doses on the titration chart (using either standard chart Appendix 3 or individual chart Appendix 4). Community initiation: May require a slower and more flexible titration than inpatients. There are 2 methods for starting clozapine. The first dose is given just before retiring; this avoids the need for close monitoring immediately after administration, then for subsequent days monitoring should take place after the morning dose with the patient taking the night time dose before retiring. The first dose may be given in the morning then monitor as per pathway for the next 6 hours; repeat for morning dose on subsequent days with the patient taking the night time dose before retiring. Order initial supply from Pharmacy indicating intended start date First dose should commence within ten days of the baseline blood sample Notify patient s GP Notify Trust Pharmacy team to ensure patient added to evcb Set up arrangements for seeing the patient everyday during the early titration phase to monitor side effects Set up arrangements for collection/delivery of medicines to support adherence with treatment Complete intervention plan and give a copy to the patient
Day 1 Immediately prior to first dose of clozapine the following physical assessments should be carried out: BP Temperature Pulse If any abnormalities or concerns results should be discussed with medical staff prior to administration of clozapine. Administer first dose of clozapine (ensure this is within 10 days of baseline blood test) The following should be recorded: NB Monitoring BP, temperature and pulse is not required if the first dose is given at night. Blood pressure Temperature Pulse Weight 1 hour 2 hour 3 hour 4 hour 5 hour 6 hour Patient provided with out of hours contact details Week 1 (Days 2 to 7) & Week 2 Once in the week, patient blood sample obtained and sent to: Near patient testing unit CPMS Local haematology labs (WCC and differential count) Date of next blood test arranged Next seven days of treatment are prescribed on the titration chart Order next supply of clozapine from Lloydspharmacy/acute trust If sample sent to local haematology lab notify CPMS (0845 7698269) of results or enter results onto ecpms (WBC; platelets; absolute neutrophils) Confirm GREEN blood result on CPMS system and confirm result/attendance on evcb. If AMBER or RED refer to appendix 1 or 2 Post morning dose monitoring Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Blood pressure Temperature Pulse Weight Blood pressure Temperature Pulse Weight Day 8 Day 9 Day 10 Day 11 Day 12 Day 13 Day 14 Clozapine supply for remainder of validity collected by patient/care coordinator (supplies issued by Lloydspharmacy will be dispensed into daily venalink packs during the titration period)
Discuss common side effects with client (sedation, hyper salivation, constipation, seizures, nausea, nocturnal enuresis) and report any problems in increase in side effects to medical staff. Brief assessment of mental state completed, including mood, thinking and behaviour Weeks 3 to 18 (weekly blood monitoring and supplies) Weeks 19 to 52 (two weekly blood monitoring and supplies) Weeks 53+ (four weekly blood monitoring and supplies) Patient blood sample obtained and sent to: CPMS Near patient testing unit Local haematology labs (WCC and differential count) Date of next blood test arranged Treatment prescribed on the titration chart until dose stabilised. Order next week/two week/four week supply of clozapine from Lloydspharmacy/acute trust. Once dose stabilised, contact Trust/Lloydspharmacy/acute trust for generation of a six month repeat prescription If sample sent to local haematology lab notify CPMS (0845 7698269) of results or enter results onto ecpms (WBC; platelets; absolute neutrophils) Confirm GREEN blood result on CPMS system and confirm result/attendance on evcb. If AMBER or RED please refer to appendix 1 or 2 Observations completed and recorded on PARIS: Pulse: BP: Temp: Weight: At week twelve do ECG, Blood Glucose and lipids Discuss common side effects with client (sedation, hyper salivation, constipation, seizures, nausea, nocturnal enuresis) and report any problems in increase in side effects to medical staff. Brief assessment of mental state completed, including mood, thinking and behaviour Clozapine serum levels should be measured as a minimum annually but can be measured more frequently at the request of the prescriber, results should be interpreted following the trust clozapine plasma assay guidance. Issue supply of clozapine to patient /direct patient to Lloyds branch where appropriate Dose Changes Lloydspharmacy/Acute trust and Trust Pharmacy Team must be notified of all dose changes via prearranged notification method in order for a new 6 month repeat prescription to be generated All dose changes to clozapine and any co-meds prescribed within the trust must be recorded on PARIS
Advice on temporary breaks in treatment Up to 18 weeks Dose Dose on Break Dose on restart discontinuation Any <48 hours Document in patient record and restart on previous Any >48 hours but less than one week dose, discuss adherence Notify CPMS of break in treatment and restart at 12.5-25mg and build up gradually to previous dose to minimise dose-related side effects. Re-assess clinical effectiveness when previous dose reached Sampling frequency Previous Break Monitoring on re-start monitoring frequency Weekly < 1 week Weekly, no need to restart 18-week period Weekly > 1 week Weekly, must restart 18-week period Fortnightly < 3 days Fortnightly Fortnightly > 3 days Weekly for 6 weeks then fortnightly 4-weekly < 3 days Four-weekly 4-weekly > 3 days Weekly for 6 weeks then four-weekly Fortnightly / 4-wkly > 4 weeks Weekly for 18 weeks, then resume on previous frequency NB. Notify Trust Pharmacy team of any changes in monitoring frequency to ensure evcb is updated accordingly. Discontinuation of Clozapine Therapy (refer to Appendix 2 for red results) Decision to stop clozapine has been made with full discussion with MDT and user/carer regarding possible consequences. Stop due to: Patient preference Non-compliance with medication/blood monitoring Symptom remission Lack of efficacy Side effects Gradual withdrawal regime discussed with user/carer Continue to monitor bloods for one month at previous monitoring frequency e.g. 4 x 1/52, 2 x 2/52, or 1 x 4/52 Patient blood sample obtained and sent to: Near patient testing unit CPMS Local haematology labs (WCC and differential count) Date of next blood test arranged If sample sent to local haematology lab notify CPMS (0845 7698269) of results or enter results onto ecpms (WBC; platelets; absolute neutrophils) Confirm GREEN blood result on CPMS system and confirm result/attendance on evcb. If AMBER or RED please refer to appendix 1 or 2 User/carer informed of clinical indications and when to seek medical advice
Discussion regarding monitoring for recurrence of psychotic symptoms and consideration of alternative medication has taken place Notify trust pharmacy and supplying pharmacy of discontinuation in order for the evcb to be updated and annotated accordingly and to ensure medication is supplied in accordance with the agreed withdrawal regime. Drug and Therapeutics Committee - Approved: September 13
Appendix 1 AMBER result Continue with usual treatment Repeat blood tests twice weekly until either RED or GREEN result obtained on subsequent tests: o GREEN result continue usual treatment o AMBER result continue twice weekly monitoring until RED or GREEN result obtained o RED result STOP treatment and repeat blood tests daily until patient recovered (see Appendix 2 RED result)
Appendix 2 RED result STOP clozapine treatment immediately and remove all supplies from patients home If sample tested on near patient testing unit, confirm result by sending the remainder of the sample to the local haematology laboratory Repeat blood tests DAILY until patient recovered/return to normal and monitor for sign of infection Confirmation of the RED blood test is recommended by performing two blood counts on two consecutive days; however, clozapine MUST be discontinued after the first blood count Once RED result confirmed, no further prescribing allowed (nonrechallengable) unless an error has occurred o Once GREEN result obtained continue blood tests at previous frequency for four weeks after stopping treatment with clozapine o RED/AMBER result repeat blood tests daily until patient recovered o Monitor for adverse physical and mental health effects of sudden discontinuation Notify Consultant and Care coordinator Notify Trust Pharmacy team and Lloydspharmacy team of RED result and discontinuation of treatment so that the evcb can be updated and annotated accordingly Further information available from CPMS
Appendix 3 CLOZAPINE STANDARD DOSE TITRATION PRESCRIPTION AND ADMINISTRATION RECORD Patients name D.O.B Consultant NHS number CPMS Number Ward/Clinical Team DAY DATE MORNING DOSE NURSE S SIGNATURE EVENING DOSE NURSE S SIGNATURE 1 12.5mg 2 12.5mg 12.5mg 3 25mg 25mg 4 25mg 25mg 5 25mg 50mg 6 25mg 50mg 7 50mg 50mg 8 50mg 75mg 9 75mg 75mg 10 75mg 100mg 11 100mg 100mg 12 100mg 125mg 13 125mg 125mg a 14 125mg 150mg 15 150mg 150mg 16 150mg 150mg 17 150mg 150mg 18 150mg 200mg b 19 150mg 200mg 20 150mg 200mg 21 200mg 200mg 22 200mg 200mg 23 200mg 200mg 24 200mg 200mg 25 200mg 200mg 26 200mg 200mg 27 200mg 200mg 28 200mg 250mg c Further increases should be made slowly in increments of 50-100mg each week, up to a maximum of 900mg per day Regular monitoring of pulse, temperature & B.P. is required Prescriber s Signature: Date: Prescriber s Name: a Target dose for female non-smokers Original to Lloydspharmacy Photocopy- use as administration record b Target dose for male non-smoker Target dose for male smokers 550mg/day c Target dose for female smokers
Appendix 4 CLOZAPINE INDIVIDUAL DOSE TITRATION PRESCRIPTION AND ADMINISTRATION RECORD Patients name D.O.B Consultant NHS number CPMS Number Ward/Clinic DAY DATE Add dose and prescriber s signature NURSE S SIGNATURE Add dose and prescriber s signature NURSE S SIGNATURE 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Further increases should be made slowly in increments of 50-100mg each week, up to a maximum of 900mg per day Regular monitoring of pulse, temperature & B.P. is required Original to Lloydspharmacy Photocopy- use as administration record Target dose for female non-smokers 250mg/day Target dose for male non-smokers 350mg/day Target dose for female smokers 450mg/day Target dose for male smokers 550mg/day