Shared Care Guidelines In partnership with Acute Trust & PCTs TACROLIMUS In renal transplant

Transcription

1 Shared Care Guidelines In partnership with Acute Trust & PCTs TACROLIMUS In renal transplant August 2016 TacrolimusGUI201609V2.0FINAL Page 0 of 17

2 Table of Contents Introduction 2 Licensing 2 Referral 2 Initiation and maintenance of therapy 3 Administration 3 Supply 3 Prescribing 3 Adverse effects 5 Contraindication 8 Drug interactions 9 Monitoring 10 Area of responsibility for the sharing of care 11 Responsibilities of the Hospital 11 Responsibilities of the GP 11 Overdose 12 Availability of Consultant and senior hospital staff 12 Additional sources of advice 12 Key points summary Tacrolimus is a macrolide immunosuppressant; it is similar in action to ciclosporin. Tacrolimus is never used in combination with ciclosporin. TacrolimusGUI201609V2.0FINAL Page 1 of 17

3 Introduction Mid Essex Hospitals Services NHS Trust (MEHT) and the local CCGs have agreed that Tacrolimus is suitable for shared-care: Prescribing status RED: For all new patients prescribing to remain with secondary care. Prescribing status AMBER: SHARED CARE for existing patients only. The objectives of these guidelines are: To provide impartial information to GPs and community pharmacists who may not have previous experience of this drug To define the procedure for referral of the patient from the hospital to the GP To define the aspects of care for which the hospital and GP are responsible To define the support available from the hospital To establish lines of communication between GPs, Consultants and senior hospital staff Contributors to these guidelines are: Dr A Chan Dr A Ali Dr S Abeygunasekara Sarah Cox Author: Renal Pharmacist Clare Drain, Medicines Information & Education & Training manager Licensing Tacrolimus is licensed for prophylaxis of transplant rejection in liver, kidney or heart allograft recipients and treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products. Referral of patients The patient will be assessed by a specialist, and the decision to commence tacrolimus therapy made. Once stable the specialist will invite the GP to undertake shared care. TacrolimusGUI201609V2.0FINAL Page 2 of 17

4 Initiation and maintenance of therapy Medication history is checked to ensure there are no contra-indications to tacrolimus therapy Blood levels of tacrolimus will be monitored Full blood counts and coagulation tests (including U&Es) ECG, blood pressure Blood glucose Liver function tests Neurological and visual status Cholesterol Plasma protein determinations Supply Three different pharmaceutical forms of oral tacrolimus products are currently available: Immediate release capsules taken twice a day (Brands: Adoport, Capexion, Prograf, Tacni and Vivadex ) Prolonged release capsule taken once daily (Advagraf ) Granules for oral solution taken twice daily (Modigraf ) Different brands of tacrolimus are NOT interchangeable. The CHM has updated its advice on the safe use of oral tacrolimus products and recommends that to avoid confusion for patients and prescribers, and to avoid inadvertent switching of product from different suppliers, all oral tacrolimus products should be prescribed by brand name only. Substitution or a change of brand should be made only under close specialist supervision. Administration/dosage Tacrolimus can be administered intravenously or orally. In general, dosing may commence orally. The capsules should be swallowed with fluid (preferably water), and only removed from their original foil blister immediately prior to administration. Capsules should generally be administered on an empty stomach or at least 1 hour before or 2 to 3 hours after a meal, to achieve maximal absorption. TacrolimusGUI201609V2.0FINAL Page 3 of 17

5 Tacrolimus immediate release preparations Prophylaxis of kidney transplant rejection adults Tacrolimus therapy using immediate release preparations should commence at micrograms/kg/day administered as two divided doses (e.g. morning and evening). Administration should commence within 24 hours after the completion of surgery. If the dose cannot be administered orally as a result of the clinical condition of the patient, intravenous therapy of micrograms/kg/day should be initiated as a continuous 24-hour infusion. Prophylaxis of transplant rejection children An initial oral dose of 300 micrograms/kg/day should be administered in two divided doses (e.g. morning and evening). If the clinical condition of the patient prevents oral dosing, an initial intravenous dose of micrograms/kg/day should be administered as a continuous 24- hour infusion. Prograf capsules may be opened and the contents mixed with water for administration via feeding tube if required. Tacrolimus doses are usually reduced in the post-transplant period. It is possible in some cases to withdraw concomitant immunosuppressive therapy, leading to tacrolimus-based dual-therapy. Post-transplant improvement in the condition of the patient may alter the pharmacokinetics of tacrolimus and may necessitate further dose adjustments. Advagraf Prolonged release preparation Advagraf must be swallowed whole and best practice dictates that it should not be removed from the foil blister until administration is about to take place. Prophylaxis of kidney transplant rejection Advagraf therapy should commence at a dose of micrograms/kg/day administered once daily in the morning. Administration should commence within 24 hours after the completion of surgery. In patients unable to take oral medicinal products during the immediate post-transplant period, tacrolimus therapy can be initiated intravenously in the form of 5 mg/ml concentrate for solution for infusion at a dose approximately 1/5 th of the recommended oral dose for the corresponding indication. Advagraf doses are usually reduced in the post-transplant period. It is possible in some cases to withdraw concomitant immunosuppressive therapy, leading to Advagraf monotherapy. Posttransplant changes in the condition of the patient may alter the pharmacokinetics of tacrolimus and may necessitate further dose adjustments. Conversion of immediate release tacrolimus-treated patients to Advagraf TacrolimusGUI201609V2.0FINAL Page 4 of 17

6 Allograft transplant patients maintained on twice daily immediate release tacrolimus dosing requiring conversion to once daily Advagraf should be converted on a 1:1 (mg:mg) total daily dose basis. When converting from immediate release tacrolimus to Advagraf, trough levels should be measured prior to conversion and within two weeks after conversion. Following conversion, tacrolimus trough levels should be monitored and if necessary dose adjustments made to maintain similar systemic exposure. Dose adjustments should be made to ensure that similar systemic exposure is maintained. Conversion from ciclosporin to tacrolimus Care should be taken when converting patients from ciclosporin-based to tacrolimus-based therapy. The combined administration of ciclosporin and tacrolimus is not recommended. Advagraf therapy should be initiated after considering ciclosporin blood concentrations and the clinical condition of the patient. Dosing should be delayed in the presence of elevated ciclosporin blood levels. In practice, tacrolimus-based therapy has been initiated hours after discontinuation of ciclosporin. Monitoring of ciclosporin blood levels should be continued following conversion as the clearance of ciclosporin might be affected. Prescribing Tacrolimus is classified as an Amber 1 medication on the traffic lights system. It is suitable for prescribing under a shared care protocol with additional biochemical monitoring requirements on a level 1 basis as per local enhanced service. Initiation of tacrolimus treatment will be made by the hospital. The hospital will perform the relevant tests before treatment is started and will supply at least the first three months of medication. Once the patient is considered to be stable the specialists will write to the GP asking for agreement to take over the responsibility for prescribing, detailing dose information and monitoring requirements. Tacrolimus is prescribable on FP10, and must only be prescribed by brand name, as per CHM guidance. Adverse effects The adverse drug reaction profile associated with immunosuppressive agents is often difficult to establish owing to the underlying disease and the concurrent use of multiple medications. Increased risk of infection (viral, bacterial, fungal, protozoal) Increased risk of developing malignancies. Benign as well as malignant neoplasms including EBV-associated lymphoproliferative disorders and skin malignancies have been reported in association with tacrolimus treatment. TacrolimusGUI201609V2.0FINAL Page 5 of 17

7 Blood and lymphatic system disorders Common: anaemia, leucopenia, thrombocytopenia, leukocytosis, red blood cell analyses abnormal Uncommon: coagulopathies, coagulation and bleeding analyses abnormal, pancytopenia, neutropenia Rare: thrombotic thrombocytopenic purpura, hypoprothrombinaemia Immune system disorders Allergic and anaphylactoid reactions have been observed in patients receiving tacrolimus (see section 4.4). Endocrine disorders Rare: hirsutism Metabolism and nutrition disorders Very common: hyperglycaemic conditions, diabetes mellitus, hyperkalaemia Common: hypomagnesaemia, hypophosphataemia, hypokalaemia, hypocalcaemia, hyponatraemia, fluid overload, hyperuricaemia, appetite decreased, anorexia, metabolic acidoses, hyperlipidaemia, hypercholesterolaemia, hypertriglyceridaemia, other electrolyte abnormalities Uncommon: dehydration, hypoproteinaemia, hyperphosphataemia, hypoglycaemia Psychiatric disorders Very common: insomnia Common: anxiety symptoms, confusion and disorientation, depression, depressed mood, mood disorders and disturbances, nightmare, hallucination, mental disorders Uncommon: psychotic disorder Nervous system disorders Very common: tremor, headache Common: seizures, disturbances in consciousness, paraesthesias and dysaesthesias, peripheral neuropathies, dizziness, writing impaired, nervous system disorders Uncommon: coma, central nervous system haemorrhages and cerebrovascular accidents, paralysis and paresis, encephalopathy, speech and language abnormalities, amnesia Rare: hypertonia Very rare: myasthenia Eye disorders Common: vision blurred, photophobia, eye disorders Uncommon: cataract Rare: blindness TacrolimusGUI201609V2.0FINAL Page 6 of 17

8 Ear and labyrinth disorders Common: tinnitus Uncommon: hypoacusis Rare: deafness neurosensory Very rare: hearing impaired Cardiac disorders Common: ischaemic coronary artery disorders, tachycardia uncommon: ventricular arrhythmias and cardiac arrest, heart failures, cardiomyopathies, ventricular hypertrophy, supraventricular arrhythmias, palpitations, ECG investigations abnormal, heart rate and pulse investigations abnormal Rare: pericardial effusion Very rare: echocardiogram abnormal Vascular disorders Very common: hypertension Common: haemorrhage, thrombembolic and ischaemic events, peripheral vascular disorders, vascular hypotensive disorders Uncommon: infarction, venous thrombosis deep limb, shock Respiratory, thoracic and mediastinal disorders Common: dyspnoea, parenchymal lung disorders, pleural effusion, pharyngitis, cough, nasal congestion and inflammations Uncommon: respiratory failures, respiratory tract disorders, asthma Rare: acute respiratory distress syndrome Gastrointestinal disorders Very common: diarrhoea, nausea common: gastrointestinal inflammatory conditions, gastrointestinal ulceration and perforation, gastrointestinal haemorrhages, stomatitis and ulceration, ascites, vomiting, gastrointestinal and abdominal pains, dyspeptic signs and symptoms, constipation, flatulence, bloating and distension, loose stools, gastrointestinal signs and symptoms Uncommon: ileus paralytic, peritonitis, acute and chronic pancreatitis, blood amylase increased, gastrooesophageal reflux disease, impaired gastric emptying Rare: subileus, pancreatic pseudocyst Hepatobiliary disorders Common: hepatic enzymes and function abnormalities, cholestasis and jaundice, hepatocellular damage and hepatitis, cholangitis Rare: hepatitis artery thrombosis, venoocclusive liver disease Very rare: hepatic failure, bile duct stenosis TacrolimusGUI201609V2.0FINAL Page 7 of 17

9 Skin and subcutaneous disorders Common: pruritus, rash, alopecias, acne, sweating increased Uncommon: dermatitis, photosensitivity Rare: toxic epidermal necrolysis (Lyell's syndrome) Very rare: Stevens Johnson syndrome Musculoskeletal and connective tissue disorders Common: arthralgia, muscle cramps, pain in limb, back pain Uncommon: joint disorders Renal and urinary disorders Very common: renal impairment Common: renal failure, renal failure acute, oliguria, renal tubular necrosis, nephropathy toxic, urinary abnormalities, bladder and urethral symptoms Uncommon: anuria, haemolytic uraemic syndrome Very rare: nephropathy, cystitis haemorrhagic Reproductive system and breast disorders Uncommon: dysmenorrhoea and uterine bleeding General disorders and administration site conditions Common: asthenic conditions, febrile disorders, oedema, pain and discomfort, blood alkaline phosphatase increased, weight increased, body temperature perception disturbed uncommon: multi-organ failure, influenza like illness, temperature intolerance, chest pressure sensation, feeling jittery, feeling abnormal, blood lactate dehydrogenase increased, weight decreased Rare: thirst, fall, chest tightness, mobility decreased, ulcer Very rare: fat tissue increased Injury, poisoning and procedural complications Common: primary graft dysfunction Contraindications Hypersensitivity to tacrolimus or other macrolides. Hypersensitivity to any of the excipients (exclude before starting therapy, if contraception required, non hormonal methods should be used) Breastfeeding Avoid concurrent administration with ciclosporin (care if patient has previously been treated with ciclosporin) TacrolimusGUI201609V2.0FINAL Page 8 of 17

10 Precautions Extra monitoring of tacrolimus concentrations is recommended during episodes of diarrhoea Patients switched to tacrolimus therapy should not receive anti-lymphocyte treatment concomitantly As with other immunosuppressive agents, owing to the potential risk of malignant skin changes, exposure to sunlight and UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor. As with other potent immunosuppressive compounds, the risk of secondary cancer is unknown. Tacrolimus preparations may contain lactose. Special care should be taken in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. The printing ink used to mark Advagraf capsules contains soya lecithin. In patients who are hypersensitive to peanut or soya, the risk and severity of hypersensitivity should be weighed against the benefit of using Advagraf. Drug Interactions Systemically available tacrolimus is metabolised by hepatic CYP3A4. There is also evidence of gastrointestinal metabolism by CYP3A4 in the intestinal wall. Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and thereby increase or decrease tacrolimus blood levels. It is therefore recommended to monitor tacrolimus blood levels whenever substances which have the potential to alter CYP3A metabolism are used concomitantly and to adjust the tacrolimus dose as appropriate in order to maintain similar tacrolimus exposure For these reasons, the combined administration of ciclosporin and tacrolimus is not recommended and care should be taken when administering tacrolimus to patients who have previously received ciclosporin Tacrolimus has been shown to increase the blood level of phenytoin. As tacrolimus may reduce the clearance of steroid-based contraceptives leading to increased hormone exposure, particular care should be exercised when deciding upon contraceptive measures. Concurrent use of tacrolimus with medicinal products known to have nephrotoxic or neurotoxic effects may increase these effects (e.g., aminoglycosides, gyrase inhibitors, vancomycin, cotrimoxazole, NSAIDs, ganciclovir or aciclovir). Enhanced nephrotoxicity has been observed following the administration of amphotericin B and ibuprofen in conjunction with tacrolimus. TacrolimusGUI201609V2.0FINAL Page 9 of 17

11 As tacrolimus treatment may be associated with hyperkalaemia, or may increase pre-existing hyperkalaemia, high potassium intake, or potassium-sparing diuretics (e.g., amiloride, triamterene, or spironolactone) should be avoided. Immunosuppressants may affect the response to vaccination and vaccination during treatment with tacrolimus may be less effective. The use of live attenuated vaccines should be avoided. Protein binding considerations Tacrolimus is extensively bound to plasma proteins. Possible interactions with other medicinal products known to have high affinity for plasma proteins should be considered (e.g., NSAIDs, oral anticoagulants, or oral antidiabetics). Monitoring Blood levels of tacrolimus - Clinical study analysis suggests that the majority of patients can be successfully managed if tacrolimus blood trough levels are maintained below 20 ng/ml. It is necessary to consider the clinical condition of the patient when interpreting whole blood levels. In clinical practice, whole blood trough levels have generally been in the range 5-20 ng/ml in liver transplant recipients and ng/ml in kidney and heart transplant patients in the early post-transplant period. Subsequently, during maintenance therapy, blood concentrations have generally been in the range of 5-15 ng/ml in liver, kidney and heart transplant recipients. During the initial post-transplant period, monitoring of the following parameters should be undertaken on a routine basis: blood pressure, ECG, neurological and visual status, fasting blood glucose levels, electrolytes (particularly potassium), liver and renal function tests, haematology parameters, coagulation values, and plasma protein determinations. If clinically relevant changes are seen, adjustments of the immunosuppressive regimen should be considered. TacrolimusGUI201609V2.0FINAL Page 10 of 17

12 Area of responsibility for the sharing of care Sharing of care assumes communication between the specialist, GP and the patient. The intention to share care should be explained to the patient and accepted by them. Officially the prescribing clinician has clinical responsibility for the medication they have prescribed. Responsibilities of the hospital Initial tests and monitoring until patient is stable on therapy Discussion with the patient regarding benefits and side effects of treatment Provide the patient with verbal and written information prior to commencing treatment To seek the co-operation of the GP in undertaking shared care of the patient, in accordance with these guidelines and in the referral letter. The opportunity for the GP and hospital consultant to further discuss the case and shared care, if required will be highlighted To provide the patient s GP with a full summary letter indicating dose and frequency before implementation of shared care Continued monitoring of treatment including drug levels and liver/renal function as agreed Prompt communication with the GP of any changes in treatment (including dose adjustments) and assessments of adverse events To provide blood test results to GP and patient Advice to GPs about all aspects of treatment including specifying review dates Reporting adverse events to the CSM Ensure clear arrangements for back-up, advice and support Responsibilities of the General Practitioner To prescribe maintenance therapy to patients To report any adverse events to the consultant and CSM Prompt referral to specialist if there is any change in patient s status Reporting to and seeking advice from the specialist on any aspect of patient care which is of concern to the GP and may affect treatment To monitor overall health and well-being and blood pressure of the patient After stabilisation to carry out blood tests including cholesterol at intervals directed by specialist TacrolimusGUI201609V2.0FINAL Page 11 of 17

13 Overdose Please always contact the poisons help line. UK National Poisons Information Service (directs caller to relevant local centre) and/or the Summary of Product Characteristics (SPC) of the Tacrolimus product (via Availability of Consultant and senior hospital staff Consultant Dr A Chan Consultant Dr S Abeygunasekara Consultant Dr A Ali Renal Pharmacist Sarah Cox Additional sources of advice Pharmacy Medicines Information Broomfield Hospital (Mon-Fri 9-4) On Call Hospital Pharmacist On Call Nephrologist (bleep via switchboard) Useful sources of information BNF (current edition) MIMS SPC for each product (via TacrolimusGUI201609V2.0FINAL Page 12 of 17

14 Initial Letter Appendix I Re: (drug name) shared care guidelines Patient s details Dear Dr I have seen this patient in clinic and believe that he/she is suitable for treatment with Drug name. I have initiated this patient on and will be prescribing and monitoring this patient at our clinics until such time that the patient is deemed stable, which is likely to be in the region of..months. I would like to seek your agreement to take over the prescribing and monitoring of this patient s treatment after this stabilisation period as per agreed shared care guidelines. A copy of the shared care guidelines is enclosed for your information. Please complete the form below and fax back to the stated safe haven fax numbers. I thank you in anticipation. Yours Sincerely Dr Consultant Enc Fax back to: Clinic/Hospital Fax PCT fax Delete as applicable I agree to take over prescribing and monitoring responsibility for this patient as per enclosed shared care guidelines from such date as the patient is deemed stable. I am not willing to undertake shared-care for this patient because. (Patient name: Hospital number: ) Yours sincerely Dr.. TacrolimusGUI201609V2.0FINAL Page 13 of 17

15 Second letter to start shared care Appendix II Re: (drug name) shared care guidelines Patient s details Dear Dr Thank you for agreeing to shared care for the above named patient as per my initial letter dated. I have been prescribing and monitoring for this patient for the past stable as per agreed shared care guidelines. and the patient is deemed The patient is doing well and is currently on (details of dosage regimen). I would like to discharge this patient to you for prescribing and monitoring of the drug and the general well being of the patient within the parameters of the shared care. I have prescribed for this patient for a further 28 days. I will continue to see this patient in clinic annually to monitor disease progress. In the mean while if there is any thing that concerns you about the patient, please do not hesitate to contact me. Yours Sincerely Dr Consultant TacrolimusGUI201609V2.0FINAL Page 14 of 17

16 To establish shared care in existing patients Appendix III Re: (drug name) shared care guidelines Patient s details Dear Dr You may already be prescribing (drug name) for the above mentioned patient. The patient is now deemed stable as per agreed shared care guidelines and is doing well. The patient is currently on (details of dosage regimen). I would like to discharge this patient to you for prescribing and monitoring of the drug and the general well being of the patient within the parameters of the shared care. I will continue to see this patient in clinic annually or as appropriate to monitor disease progress. In the mean while if there is any thing that concerns you about the patient, please do not hesitate to contact me. Yours Sincerely Dr Consultant cc. Dispensary Manager, Pharmacy Department, Broomfield Hospital Fax back to: Clinic/Hospital Fax PCT fax Delete as applicable I agree to take over prescribing and monitoring responsibility for this patient as per enclosed shared care guidelines from such date as the patient is deemed stable. I am not willing to undertake shared-care for this patient because. (Patient name: Hospital number: ) Yours sincerely Dr.. Name and address for the practice TacrolimusGUI201609V2.0FINAL Page 15 of 17

17 Title Document reference Author Approved by Date approved September 2016 Next review date September 2019 Tacrolimus Shared Care Guidelines TacrolimusGUI201609V2.0FINAL Sarah Cox, Renal Pharmacist MEHT Clare Drain, Medicines Information & Education & Training manager, MEHT APC Previous Version May 2012 Key Changes TacrolimusGUI201609V2.0FINAL Page 16 of 17