Common use of RESPONSIBILITIES and ROLES Clause in Contracts

RESPONSIBILITIES and ROLES. Specialist responsibilities Diagnosis and initiation of azathioprine treatment, ensuring that there are no interactions with current therapy or disease states. Discuss the benefits and side effects of treatment with the patient/carer, including providing the patient with information leaflets and a monitoring record book if required. If appropriate, patients should be advised about the impact of treatment on fertility, pregnancy and breastfeeding. Men planning to conceive should also receive appropriate counselling. Undertake baseline tests including weight, blood pressure, ALT (or AST), eGFR, CRP, chest X-ray and TMPT levels) prior to starting therapy. Advise patient to be vaccinated against pneumococcus and influenza infection (via GP). Notify the patients GP that treatment has started and inform results of baseline tests. Prescribe azathioprine until a stable dose is reached and blood tests are stable for three months. Contact the GP to ask whether he or she is willing to participate in shared care (once the patient is stable). Shared care can only commence when GP written consent has been received Discuss the shared care arrangement with the patient so that the patient/carer is clear what needs to be monitored and when. Where applicable advise patient treatment is off-label Dose stabilisation: initial dosage adjustment until stable. Thereafter, during maintenance treatment, advice to the GP on any further dose adjustments required. If dose and bloods are stable for 3 months the GP, if agreeable, can monitor the patient as below Periodically review the patient’s condition and communicate promptly with the GP when treatment is changed. Have a mechanism in place to receive rapid referral of a patient from the GP in the event of deteriorating clinical condition. Advise the GP on stopping treatment (if appropriate). Report serious adverse events to the MHRA and GP Ensure that clear backup arrangements exist for GPs to obtain advice and support. General Practitioner responsibilities Reply to the request for shared care as soon as practicable. File copy in patient’s record and add shared care – specialist/GP read code 66S2 or XaK6z depending on GP clinical system. Ensure compatibility with other concomitant medication and prescribe azathioprine at the dose recommended. Once patient is stable and shared care has been agreed, monitor patient as below. Adjust the dose as advised by the specialist. Report to and seek advice from the specialist on any aspect of patient care that is of concern and may affect treatment. Refer patient to the specialist if his or her condition deteriorates. Stop treatment on the advice of the specialist or immediately if an urgent need to stop treatment arises. Report adverse events to the specialist and MHRA. SUPPORTING CLINICAL INFORMATION Dosage and Administration Azathioprine is available as tablets containing 25mg or 50mg. Azathioprine should be taken with or immediately after food. The usual dose is from 1 to 3mg per kg per day, adjusted according to response. Contraindications Azathioprine is contra-indicated in patients known to be hypersensitive to it. Hypersensitivity to 6-mercaptopurine (6-MP) should alert the prescriber to probable hypersensitivity to azathioprine. Azathioprine therapy should not be initiated in patients who may be pregnant, or who are likely to become pregnant without careful assessment of risk versus benefit. Side Effects Very common - Depression of bone marrow function; leucopenia, viral, fungal, and bacterial infections, thrombocytopenia. Uncommon – cholestasis and degeneration of liver function tests, pancreatitis, anaemia. Rare – alopecia, photosensitivity, life threatening hepatic damage, colitis, diverticulitis and bowel perforation reported in transplant population; severe diarrhoea in inflammatory bowel disease population. Agranulocytosis, pancytopenia, aplastic anaemia, megaloblastic anaemia, erythroid hypoplasia. Neoplasms including non-Hodgkin's lymphomas, skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ, acute myeloid leukaemia and myelodysplasia Very rarely causes reversible pneumonitis, Xxxxxxx-Xxxxxxx syndrome and toxic epidermal necrolysis. A hypersensitivity reaction has been uncommonly reported which includes general malaise, dizziness, nausea, vomiting, diarrhoea, fever, rigors, exanthema, rash, vasculitis, myalgia, arthralgia, hypotension, renal and hepatic dysfunction and cholestasis. Following a hypersensitivity reaction, careful consideration should be given to restarting treatment with azathioprine. Monitoring FBC, creatinine / eGFR, ALT (or AST) and albumin every 2 weeks until dose and monitoring stable for 6 weeks; thereafter monthly for three months, then at least every 12 weeks. Dose increases should be monitored by FBC, creatinine / eGFR, ALT (or AST) and albumin every 2 weeks until on stable dose for 6 weeks then revert to previous schedule. Action required if abnormal results Contact specialist team urgently and consider interruption in treatment if any of the following develop: • WCC <3.5 x109/L • Neutrophils <1.6 x 109/L • Unexplained eosinophilia >0.5 x 109/L • Platelet count <140 x 109/L • MCV > 105 f/L • Creatinine >30% above baseline and/or calculated GFR <60 • ALT and/or AST >100 units/L • Unexplained fall in serum albumin Drug Interactions Xanthine oxidase activity is inhibited by allopurinol, oxipurinol and thiopurinol which results in reduced conversion of biologically active 6-thioinosinic acid to biologically inactive 6-thiouric acid. When allopurinol, oxipurinol and/or thiopurinol are given concomitantly with 6-mercaptopurine or azathioprine, the dose of 6-mercaptopurine and azathioprine should be reduced to one-quarter of the original dose. Inhibition of the anticoagulant effect of warfarin, when administered with azathioprine, has been reported. Where possible, concomitant administration of cytostatic drugs, or drugs which may have a myelosuppressive effect, such as penicillamine, should be avoided. There are conflicting clinical reports of interactions, resulting in serious haematological abnormalities, between Imuran and co-trimoxazole. Olsalazine, mesalazine and sulfasalazine may inhibit TPMT enzyme, resulting in an increased toxicity.

RESPONSIBILITIES and ROLES. Specialist clinician responsibilities Diagnosis and initiation of azathioprine treatment, ensuring that there are no interactions with current therapy or disease states. 1 Discuss the benefits and side effects of treatment with the patient/carer, including providing the . 2 Check for possible drug interactions with mycophenolate and patients regular medication. Avoid prescribing interacting drugs. 3 Assess likelihood of compliance. 4 Ensure patient with is given sufficient information leaflets and a monitoring record book if requiredabout their treatment. If appropriate, patients should be advised about the impact of treatment on fertility, pregnancy and breastfeeding. Men planning to conceive should also receive appropriate counselling. Undertake 5 Perform all baseline tests (including weightFBC, blood pressure, ALT (or AST), eGFR, CRP, chest X-ray U&Es and TMPT levels) prior to starting therapy. Advise patient to be vaccinated against pneumococcus and influenza infection (via GPLFTs). Notify the patients GP that 6 Initiate and stabilise treatment has started and inform results of baseline testswith mycophenolate. Prescribe azathioprine Stabilisation will usually take 4 weeks. 7 Supply medication until a stable dose care is reached and blood tests are stable for three monthstransferred to GP. Contact 8 Ask the GP to ask whether he or she is willing to participate in shared care (once and explain the patient is stable). Shared intention to share care can only commence when GP written consent has been received Discuss the shared care arrangement with the patient so that the patient/carer is clear what needs and obtain consent. 9 Monitors appropriately as stated on the monitoring requirement. 10 Inform GP of the dose to be monitored prescribed, any changes in dose, when to stop treatment and whenwhen to refer the patient back to specialist clinician. Where applicable advise patient treatment is off-label Dose stabilisation: initial dosage adjustment until stable11 Ensure GP has access to blood results for information. Thereafter, during maintenance treatment, advice 12 Monitor for side effects and report adverse events to the MHRA and GP on any further dose adjustments requiredwhere appropriate. If dose 13 Inform GP if patient does not attend specialist clinician appointments and bloods are stable for 3 months the GP, if agreeable, can monitor the patient as below Periodically review the patient’s condition and communicate promptly with the GP when treatment is changedaction to be taken. 14 Have a mechanism in place to receive rapid referral of a patient from the GP in the event of deteriorating clinical condition. Advise the GP on stopping treatment (if appropriate). Report serious adverse events to the MHRA and GP 15 Ensure that clear backup arrangements exist for GPs to obtain advice and support. General Practitioner responsibilities 1 Reply to the request for shared care as soon as practicablepossible. File copy in patient’s record and add shared care – specialist/GP read code 66S2 or XaK6z depending 2 Prescribe mycophenolate at the dose recommended once patient is established on GP clinical systemtreatment. 3 Ensure compatibility with other concomitant medication and prescribe azathioprine at the dose recommendedmedication. Once patient is stable and shared care has been agreed, monitor patient as below. 4 Adjust the dose as advised by the specialistspecialist clinician. Report to and seek advice from 5 Contact the specialist on any aspect of clinician if you suspect the patient care that is of concern not complying with their medication. 6 Check for possible drug interaction when prescribing new medication and may affect treatmentavoid prescribing interacting drugs. Refer patient to the specialist if his or her condition deteriorates. 7 Stop treatment on the advice of the specialist clinician or immediately if an urgent need to stop treatment arises. 8 Refer the patient to the specialist clinician if his/her condition deteriorates. 9 Report any suspected adverse events to specialist team and any severe adverse events to MHRA. Patient's / Xxxxx’s role 1 Take mycophenolate as recommended by specialist clinician. 2 Report to the specialist clinician or GP if he / she does not have a clear understanding of the treatment. 3 Request repeat prescriptions from the GP at least 5 days before the next supply is needed. 4 Attend scheduled appointments with specialist clinician, GP and MHRAfor monitoring. SUPPORTING CLINICAL INFORMATION Dosage and Administration Azathioprine is available as tablets containing 25mg 5 Share any concerns in relation to treatment with GP or 50mgspecialist clinician. Azathioprine should be taken with 6 Inform specialist clinician or immediately after food. The usual dose is from 1 to 3mg per kg per dayGP of any other medication being taken, adjusted according to response. Contraindications Azathioprine is contraincluding over-indicated in patients known to be hypersensitive to the-counter products 7 Inform specialist clinician or GP if you feel you are having problems taking your medication or have stopped taking it. Hypersensitivity 8 Report any adverse effects to 6the specialist clinician or GP. Written by (clinician): Xx Xxx Xxxxxxx Written by (pharmacist): Xxxxxx Xxxxxxx Date of issue: Mar 2020 Approved by North Staffordshire & Stoke-mercaptopurine on-Trent Area Prescribing Committee: 26/02/2020 (6-MPnew) should alert Review Date: Feb 2023 Version number: 1.2 SUPPORTING INFORMATION EFFECTIVE SHARED CARE AGREEMENT Information on therapeutic indication, dosage, method of administration, side effects and management considerations in special populations can be found in the prescriber to probable hypersensitivity to azathioprine. Azathioprine therapy should not be initiated in patients who may be pregnant, Summary of Product Characteristics for mycophenolate available from xxx.xxxxxxxxx.xxx.xx Monitoring requirements Monitoring Interval Full blood count LFTs U&Es Albumin GP or who are likely to become pregnant without careful assessment of risk versus benefit. Side Effects Very common - Depression of bone marrow function; leucopenia, viral, fungal, and bacterial infections, thrombocytopenia. Uncommon – cholestasis and degeneration of liver function tests, pancreatitis, anaemia. Rare – alopecia, photosensitivity, life threatening hepatic damage, colitis, diverticulitis and bowel perforation reported in transplant population; severe diarrhoea in inflammatory bowel disease population. Agranulocytosis, pancytopenia, aplastic anaemia, megaloblastic anaemia, erythroid hypoplasia. Neoplasms including non-Hodgkin's lymphomas, skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ, acute myeloid leukaemia and myelodysplasia Very rarely causes reversible pneumonitis, Xxxxxxx-Xxxxxxx syndrome and toxic epidermal necrolysis. A hypersensitivity reaction has been uncommonly reported which includes general malaise, dizziness, nausea, vomiting, diarrhoea, fever, rigors, exanthema, rash, vasculitis, myalgia, arthralgia, hypotension, renal and hepatic dysfunction and cholestasis. Following a hypersensitivity reaction, careful consideration should be given to restarting treatment with azathioprine. Monitoring FBC, creatinine / eGFR, ALT (or AST) and albumin every Specialist clinician Baseline ✓ ✓ ✓ ✓ Specialist clinician Every 2 weeks until during dose titration and monitoring stable for 6 weeks; thereafter monthly for three months, then at least every 12 weeks. Dose increases should be monitored by FBC, creatinine / eGFR, ALT (or AST) and albumin every 2 weeks until on stable dose for 6 weeks then revert to previous scheduleat stable dose ✓ ✓ ✓ ✓ Specialist clinician Every month for 3 months ✓ ✓ ✓ ✓ Specialist clinician Every 3 months ✓ ✓ ✓ ✓ Specialist clinician Additional information which cannot be found in the SPC Reference BSR and BHPR guideline for the prescription and monitoring of non- biologic disease-modifying anti- rheumatic drugs 2017 Rheumatology 56:865-868 xxxxx://xxx.xxxx.xxx.xx/advice/esuom36/chapter/Key-points-from-the-evidence xxxxx://xxx.xxxx.xxx.xx/advice/esuom32/chapter/Key-points-from-the-evidence xxxxx://xxx.xxxxxxxxxxxxxxx.xxx/cdsr/doi/10.1002/14651858.CD002922.pub3/abstract BACK-UP ADVICE AND SUPPORT Contact details Telephone No. Action required if abnormal results Contact specialist team urgently and consider interruption in treatment if any of the following developEmail Helpline: • WCC <3.5 x109/L • Neutrophils <1.6 x 109/L • Unexplained eosinophilia >0.5 x 109/L • Platelet count <140 x 109/L • MCV > 105 f/L • Creatinine >30% above baseline and/or calculated GFR <60 • ALT and/or AST >100 units/L • Unexplained fall in serum albumin Drug Interactions Xanthine oxidase activity is inhibited by allopurinol, oxipurinol and thiopurinol which results in reduced conversion of biologically active 601782 673687 Xxxxxxxxxxxxxxxxxxx.XXXX@xxx.xxx For urgent advice ask for Rheumatology consultant or SpR on-thioinosinic acid to biologically inactive 6-thiouric acid. When allopurinol, oxipurinol and/or thiopurinol are given concomitantly with 6-mercaptopurine or azathioprine, the dose of 6-mercaptopurine and azathioprine should be reduced to one-quarter of the original dose. Inhibition of the anticoagulant effect of warfarin, when administered with azathioprine, has been reported. Where possible, concomitant administration of cytostatic drugs, or drugs which may have a myelosuppressive effect, such as penicillamine, should be avoided. There are conflicting clinical reports of interactions, resulting in serious haematological abnormalities, between Imuran and co-trimoxazole. Olsalazine, mesalazine and sulfasalazine may inhibit TPMT enzyme, resulting in an increased toxicity.call 00000 000000 Pharmacy (MPFT): 01782 673767

RESPONSIBILITIES and ROLES. Specialist responsibilities Diagnosis and initiation of azathioprine sulfasalazine treatment, ensuring that there are no interactions with current therapy or disease states. Discuss the benefits and side effects of treatment with the patient/carer, including providing the patient with information leaflets and a monitoring record book if required. Where applicable advise patient treatment is unlicensed Undertake baseline tests including weight, blood pressure, ALT (or AST), eGFR prior to starting therapy. If appropriate, patients should be advised about the impact of treatment on fertility, pregnancy and breastfeeding. Men planning to conceive should also receive appropriate counselling. Undertake baseline tests including weight, blood pressure, ALT (or AST), eGFR, CRP, chest X-ray and TMPT levels) prior to starting therapy. Advise patient to be vaccinated against pneumococcus and influenza infection (via GP). Notify the patients GP that treatment has started and inform results of baseline teststest. Prescribe azathioprine sulfasalazine until a stable dose is has been reached and blood tests are stable for three months. Contact the GP to ask whether he or she is willing to participate in shared care (once the patient is stable). Shared care can only commence when GP written consent has been received received. Discuss the shared care arrangement agreement with the patient so that the patient/carer is clear what needs to be monitored and when. Where applicable advise patient treatment is off-label Dose stabilisation: initial dosage adjustment until stable. Thereafter, during maintenance treatment, advice to the GP on any further dose adjustments required. If dose and bloods are stable for 3 months the GP, if agreeable, can monitor the patient as below below. Periodically review the patient’s condition patient and communicate promptly in writing with the GP when treatment is changed. changed Have a mechanism in place to receive rapid referral of a patient from the GP in the event of deteriorating clinical condition. Advise the GP on stopping treatment (if appropriate). Report serious adverse events to the MHRA and GP GP. Ensure that clear backup arrangements exist for GPs to obtain advice and support. General Practitioner responsibilities Reply to the request for shared care as soon as practicable. File copy in patient’s record and add read code shared care – specialist/GP read code 66S2 or XaK6z depending on GP clinical system. Ensure compatibility with other concomitant medication and prescribe azathioprine sulfasalazine at the dose recommended. Once patient is stable and shared care has been agreed, monitor patient as below. Adjust the dose as advised by the specialist. Report to and seek advice from the specialist on any aspect of patient care that is of concern and may affect treatment. Refer patient to the specialist if his or her condition deteriorates. Stop treatment on the advice of the specialist or immediately if an urgent need to stop treatment arises. Report adverse events to the specialist and MHRA. SUPPORTING CLINICAL INFORMATION Dosage and Administration Azathioprine is available as tablets containing 25mg or 50mg. Azathioprine should be taken with or immediately after food. The Treatment of ulcerative colitis – the usual dose is from 1 1-2g four times daily for a moderate to 3severe attack, in conjunction with steroids. For a mild attack the dose is normally 1g four times daily, with a reduction to maintenance doses to 2g daily in divided doses. The same schedule of dosing is used for Crohn’s disease. Adequate fluid intake should be ensured during treatment as sulfasalazine causes crystalluria and kidney stone formation. Treatment of rheumatoid arthritis – starting dose is 500mg per kg per dayenteric coated tablet daily, adjusted according to responseincreased by one tablet each week until a maximum dose of 2g is reached. Adequate fluid intake should be ensured during treatment as sulfasalazine causes crystalluria and kidney stone formation. Contraindications Azathioprine is contra-indicated in patients Infants under the age of 2 years. Patients with a known to be hypersensitive to it. Hypersensitivity to 6-mercaptopurine (6-MP) should alert the prescriber to probable hypersensitivity to azathioprine. Azathioprine therapy should not be initiated in patients who may be pregnant, sulfasalazine Its metabolites or who are likely to become pregnant without careful assessment many of risk versus benefitthe excipients as well as sulfonamides or salicyclates Patients with porphyria. Side Effects Very The most common - Depression side effects with sulfasalazine are nausea, headache, rash, loss of bone marrow function; appetite and raised temperature. Blood disorders such as leucopenia, viralthrombocytopenia, fungal, and bacterial infections, thrombocytopenia. Uncommon – cholestasis and degeneration of liver function tests, pancreatitis, anaemia. Rare – alopecia, photosensitivity, life threatening hepatic damage, colitis, diverticulitis and bowel perforation reported in transplant population; severe diarrhoea in inflammatory bowel disease population. Agranulocytosis, pancytopeniaagranulocytosis, aplastic anaemia, haemolytic anaemia, Heinz body anaemia, hypoprothrombinaemia, lymphadenopathy, macrocytosis, megaloblastic anaemia, erythroid hypoplasiamethaemoglobinaemina, neutropenia and pancytopenia have been reported. Neoplasms including non-Hodgkin's lymphomasInsomnia, skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ, acute myeloid leukaemia and myelodysplasia Very rarely causes reversible pneumonitis, Xxxxxxx-Xxxxxxx syndrome and toxic epidermal necrolysis. A hypersensitivity reaction has been uncommonly reported which includes general malaisedepression, dizziness, nauseataste disorders, vomitingtinnitus, diarrhoeaconjunctival and scleral infection. Cough, feverstomatitis, rigors, exanthema, rash, vasculitis, myalgiapruritis, arthralgia, hypotension, renal fever have also been commonly reported Hepatic failure and hepatic dysfunction hepatitis may occur. Oligospermia and cholestasisinfertility may occur in men treated with sulfasalazine. Following a hypersensitivity reaction, careful consideration should be given Discontinuation of the drug appears to restarting treatment with azathioprine. reverse these effects within 2 to 3 months Monitoring FBC, creatinine / eGFR, ALT (or AST) and albumin every 2 weeks until dose and monitoring stable for 6 weeks; thereafter monthly for three months, then at least every 12 weeks. Monitoring can cease in patients who have been stable for 12 months. Dose increases should be monitored by FBC, creatinine / eGFR, ALT (or AST) and albumin every 2 weeks until on stable dose for 6 weeks then revert to previous schedule. Action required if abnormal results Contact specialist team urgently and consider interruption in treatment if any of the following develop: • WCC <3.5 x109/L • Neutrophils <1.6 x 109/L • Unexplained eosinophilia >0.5 x 109/L • l Platelet count <140 x 109/L • MCV > 105 f/L • Creatinine >30% above baseline and/or calculated GFR <60 • 60ml/min ALT and/or AST >100 units/L • Unexplained fall in serum albumin albumin<30g/l As well as responding to absolute values in laboratory tests, it is also relevant to observe trends in results (e.g. gradual decreases in white blood cells or albumin, or increasing liver enzymes). Drug Interactions Xanthine oxidase activity is inhibited by allopurinol, oxipurinol and thiopurinol which results in reduced conversion of biologically active 6-thioinosinic acid to biologically inactive 6-thiouric acid. When allopurinol, oxipurinol and/or thiopurinol are given concomitantly with 6-Bone marrow suppression may occur when mercaptopurine or azathioprine, the dose of 6-mercaptopurine and its prodrug azathioprine should be reduced to one-quarter of the original dose. Inhibition of the anticoagulant effect of warfarin, when administered are used in combination with azathioprine, has been reported. Where possible, concomitant administration of cytostatic drugs, or drugs which may have a myelosuppressive effect, such as penicillamine, should be avoided. There are conflicting clinical reports of interactions, resulting in serious haematological abnormalities, between Imuran and co-trimoxazole. Olsalazine, mesalazine and sulfasalazine may inhibit TPMT enzyme, resulting in an increased toxicitysulfasalazine.