Document Reference MM 050 Integrated Care Pathway (ICP) for the Management of clozapine GENERAL PRACTITIONER (GP) SUPPORT PACK One pack to be printed for each patient initiated on clozapine treatment, completed and sent to the patient s GP. Letter template Side effects of clozapine Drug interactions Risks of neutropenia and agranulocytosis Substance use and misuse References Approved by the Horizon Scanning and Prescribing Guidance sub group 23 November 2012 Review date: 23 November 2015
Ward/ Team address: Ask for: Direct line: Date: Dear Dr RE: Name: Address: DOB: I am writing to inform you that the patient detailed above has been commenced on clozapine (Clozaril) by their psychiatrist. Following a detailed assessment of their physical and mental health needs a decision has been made to commence clozapine supported by: (please tick box) Home Treatment Team Inpatient admission Medication will be supplied by the hospital as will mandatory blood tests, once discharged we will inform you of the patient s progress during the initiation phase and outline all the physical health checks that will need to be completed to ensure the patient remains physically well. Please ensure your records are updated to highlight that this patient is prescribed clozapine (Clozaril) and I hope you find the following information useful. If you have any further questions please do not hesitate to contact us. Clozaril Patient Monitoring Service (CPMS): 08457 698269
Side effects of clozapine (Clozaril) Side effect Likely time frame Suggested management Constipation Any time during treatment Cases of gastrointestinal obstruction have occurred. Advise close monitoring and prevention, adjust diet. Stool softener, bulk laxative. Drowsiness Usually within first 4 weeks Increase dose slowly. Give more of the dose at bedtime. Fever First 3 weeks Eliminate infectious causes. Consider checking full blood count. An antipyretic may be beneficial. Hypersalivation Appears early in treatment (1-4 weeks) but can persist Prop up pillows. Use a towel to cover pillow. Refer to hospital for advice. No licensed preparations available. Hypotension First 4 weeks Slow dose titration. Advise patient to stand slowly. Give largest daily dose at bedtime. Nausea/ vomiting After 4-6 weeks Refer to hospital for consideration of dose reduction and/ or plasma level monitoring. If severe consider antiemetic. Seizures Can occur at any time Dose related. Incidence greater (4.4%) at doses above 600mg daily. Refer to hospital for advice. Tachycardia Weight gain Early on in treatment. Can continue throughout treatment Anytime during treatment. (Can be 2-25 lbs.) Slow titration. Often responds to a dose reduction. In extreme cases a beta-blocker is beneficial. Dietary counselling, monitoring, exercise.
Drug interactions This list is not exhaustive and other reference sources may need to be accessed. Avoid Examples Antimicrobial, antifungal and antibiotic drugs which can cause neutropenia and agranulocytosis Consider the need for urgent full blood count. Cephalosporins Clindamycin Sulphonamides Trimethoprim Isoniazid Rifampicin Dapsone Metronidazole Tinidazole 4-quinolones Nitrofurantoin Chloramphenicol Antimicrobial drugs which increase clozapine plasma levels Erythromycin Consider the need for urgent full blood count. Other drugs which can cause neutropenia or agranulocytosis Other antipsychotics Carbamazepine Cytotoxic drugs Co-trimoxazole Chloramphenicol Analgesics Penicillamine Sulphonamides Trimethoprim Drugs which may increase clozapine plasma levels Erythromycin Cimetidine Fluvoxamine Fluoxetine Paroxetine Drugs which may decrease clozapine plasma levels Phenytoin Drugs which increase risk of neuroleptic malignant syndrome (NMS) Lithium carbonate Drugs which increase risk of circulatory collapse Benzodiazepines Clozapine may affect the plasma levels of: Warfarin Digoxin
Risks of neutropenia and agranulocytosis The incidence of neutropenia during treatment is approximately 3% with 0.5% of patients developing agranulocytosis. Patients are told to report to the hospital or their GP if they develop signs of neutropenia or infection. If a patient presents with signs of neutropenia including: sore throat temperature mouth ulcers unexplained bruising Please send a full blood count for urgent analysis. The result of the blood test should be telephoned through to the CPMS telephone number 08457 698269. Substance use and misuse Smoking cessation has been reported to increase clozapine levels by up to 73% (Thompson, 2007), since cigarette smoke is an inducer of the cytochrome P450 system. If your patient wants to quit/ reduce smoking then inform the mental health team. A dose reduction may be appropriate when stopping smoking. Side effects should be reviewed regularly during the period of cutting down. Plasma clozapine concentration is increased by caffeine intake and decreased by 50% following a 5-day caffeine free period (Novartis, 2007). Advise patient to maintain a stable caffeine intake and inform mental health team of any changes. It is officially recommended that people taking clozapine should not drink alcohol. This is because both clozapine and alcohol can cause drowsiness. References Novartis, 2007; Summary of Product Characteristics https://www.clozaril.co.uk Thompson, B., 2007; Guidance of tobacco smoking cessation on prescribed medication. (From Lancashire Care NHS Trust Clozapine Initiation Protocol) G/TGH/HQSecs/TD/LS/Clinical procedures/ Clozapine ICP. GP support pack. Version 3. November 2012