Apprved by the Bedfrdshire and Lutn Jint Prescribing Cmmittee (JPC) December 2013, Review date December 2016 Bedfrdshire and Lutn Jint Prescribing Cmmittee Shared Care Prtcl fr the prescribing and mnitring f maintenance dses f azathiprine in Inflammatry Bwel Disease This prtcl applies t patients under the care f Lutn & Dunstable Hspital Azathiprine Therapy Brief Summary The Sandz brand f azathiprine is licensed fr the treatment f inflammatry bwel disease hwever ther brands are nt licensed fr this indicatin. The use f azathiprine in inflammatry bwel disease is widely established and is supprted by natinal guidelines (BSG 2011 and NICE Crhn s disease CG 152). Clinicians shuld cnsult the full Shared Care Guideline, current BNF and SPC s fr full infrmatin. T ensure the safe use f azathiprine it is crucial that there is a gd, rbust 2-way cmmunicatin f prescribing infrmatin and bld test results between the Specialist and the GP. It is als imprtant that the patient cmmunicates with bth the Specialist and the GP. Under this shared care agreement, the GP will accept respnsibility fr prescribing azathiprine nce the patient is n a stable maintenance dse f azathiprine. The Specialists at the L&D will retain the respnsibility fr arranging fr the rutine mnitring f bld tests t be dne in the hspital. (On ccasins, where the patient is nt willing / unable t attend the hspital t receive a bld test frm frm the Specialist, the GP shuld be asked t issue the bld test frms and t send a cpy f the results t the Specialist. The prcess f the GP issuing the bld test frms n such ccasins shuld be agreed between the Specialist and the GP n an individual basis) Regardless that the bld mnitring will cntinue t be arranged by the Specialist, the GP as the prescribing clinician is respnsible fr ensuring that the bld test results are checked PRIOR t issuing a prescriptin fr the medicatin. NB: The majrity f GP s will be able t access bld test results electrnically (via ICE) when they need t check the results prir t issuing a prescriptin. If a GP des nt have access t the ICE system, then the Specialist will be required t send a paper cpy f the bld test results t the GP, in a timely manner t enable the GP t check the results prir t issuing a prescriptin. Page 1 f 8
Patient s Name: Date f Birth: NHS Number: Patient s Address: Cnsultant s Name: Cnsultant s Cntact Details: GP s Name: GP s Cntact Details: Patient s diagnsis: Drug dse, frmulatin and frequency: Severe r mderately severe inflammatry bwel disease (Crhn s r Ulcerative Clitis) in patients wh are intlerant t sterids r wh are dependent n sterids and in whm the therapeutic respnse is inadequate despite treatment with high dses f sterids Usually started at 50mg and increased t between 2 2.5mg /kg daily by muth (exact maintenance dse will depend n patient s TPMT level, clinical respnse, side effect prfile and haematlgical tlerance). Available as 25mg and 50mg film-cated tablets. Tablets cntain lactse. (NB If tablets need t be halved, advise that the tablets need t be handled in strict accrdance with guidance fr handling cyttxic agents.) Cntra-indicatins TPMT deficiency (exact level will vary depending n hspital labratry) Haemtlgical impairment (see bld test mnitring sectin) Hypersensitivity t azathiprine, 6-mercaptpurine (metablite f azathiprine) r t any f the excipients. Severe infectins. Severely impaired hepatic r bne-marrw functin. Severe hepatic impairment Pancreatitis. Any live vaccine e.g. ral pli, MMR, BCG, yellw fever. Pregnancy unless the benefits utweigh the risks (see SPC) Lactatin Patients with hereditary hypxanthine-guanine-phsphribsyl transferase deficiency (Lesch-Nyhan syndrme). Patients with rare hereditary prblems f galactse Page 2 f 8
intlerance, the Lapp lactase deficiency r glucse-galactse malabsrptin (as tablets cntain lactse). Cautins Bld test mnitring is essential when prescribing azathiprine. Renal impairment Bth a reductin in dse and increased frequency f bld test mnitring may be required. Mild t mderate hepatic impairment - Bth a reductin in dse and increased frequency f bld test mnitring may be required. Patients must infrm GP / Specialist immediately abut ral ulceratins, ulceratins f the thrat, recurrent sre thrats, fever, infectins, bruising, bleeding r ther signs f myelsuppressin. Cautin if c-prescribe with certain medicatins (see drug interactin sectin) Patients wh have nt had expsure t Varicella zster (patient shuld reprt any expsure t chickenpx r shingles urgently t GP. Advise patient t use sunscreens and prtective clthing t reduce risk f skin cancer Cautin in withdrawal f azathiprine as may result in a severe wrsening f disease. Withdrawal shuld be a gradual prcess under clse mnitring. (If immediate withdrawal needed due t abnrmal bld results / side effects, discuss with Specialist) Pregnancy & Lactatin The SPC states that azathiprine is cntraindicated in pregnancy unless the benefits utweigh the risks. The SPC als states azathiprine is cntraindicated in breastfeeding. The British Sciety f Gastrenterlgists (BSG) fllws different recmmendatins. GP s shuld refer any pregnant patients/ breastfeeding patients r patients cnsidering pregnancy t the Specialist. Page 3 f 8
Side effects: Refer t BNF /SPC fr further side effects. Hypersensitivity reactins - (including malaise, dizziness, vmiting, diarrhea, fever, rigrs, myalgia, arthralgia, rash, hyptensin and interstitial nephritis calls fr immediate withdrawal) Bne marrw suppressin (leucpenia, anaemia, thrmbcytpenia) Increased risk f pprtunistic infectins Liver impairment Chlestatic jaundice Hepattxicity (hepatic necrsis, biliary stasis) Anrexia, nausea, vmiting Oral ulceratin, rarely gastrintestinal ulceratin Increase risk f certain types f skin cancer / lymphma (see SPC fr mre details) Pancreatitis, interstitial nephritis, pneumnitis, hepatic vencclusive disease, lymphma, red cell aplasia Alpecia Drug interactins Refer t BNF / SpC fr further Drug interactins Serius Interactins Allpurinl, (xipurinl r thipurinl*) NB: Due t severity f interactin, GPs shuld cntact the Specialist fr advice befre starting a patient n allpurinl, (xipurinl r thipurinl*). (* xipurinl and thipurinl are nt licensed in the UK but culd pssibly be btained n a named patient basis) Trimethprim / c-trimxazle Clse mnitring f FBC is required (increased risk f haematlgical txicity). Warfarin anticagulant effects f warfarin and ther cumarins pssible reduced. The dse f warfarin may need t be adjusted when starting r stpping azathiprine. Ribavarin myelsuppressive effects f azathiprine are pssibly enhanced. Febuxstat AVOID cncmitant use with azathiprine. Clzapine - AVOID cncmitant use with azathiprine as increased risk f agranulcyctsis. (NB This interactin is nt specifically listed fr azathiprine hwever it is listed as a serius interactin under the 6-mercaptpurine entry in the BNF). Other interactins Clse mnitring f bld cunts is required with cncmitant use : Allpurinl, (xipurinl, thipurinl*) (see abve) Aminsalicylates e.g. mesalazine, lsalazine r sulfasalazine ACE inhibitrs Cimetidine Indmethacin (NB: Patients with IBD shuld nt be prescribed indmethacin) Agents with cyttxic/myelsuppressive prperties Page 4 f 8
BLOOD TEST MONITORING TO BE ARRANGED BY THE HOSPITAL SPECIALIST AT THE REQUIRED FREQUENCY. GP REQUIRED TO CHECK BLOOD TEST RESULTS PRIOR TO ISSUE OF ANY PRESCRIPTION FOR AZATHIOPRINE. Bld Test Mnitring requirements and frequency GP t check the bld results prir t issue f a prescriptin f azathiprine. Specialists t arrange fr bld tests t be carried ut at the hspital at the frequency stated belw and arrange fr the GP t have access t the results (either electrnically via ICE r send a paper cpy) Mnitr FBC, U&E, LFT, amylase every 3 mnths Mnitr TFT every 6 mnths After a dse change: Revised frequency f bld test mnitring required discuss with Specialist. Situatins where mre frequent bld mnitring may be required cntinuing dwnward trend in WBC r neutrphil cunt After a dse change Renal impairment Mild t mderate hepatic impairment Elderly patients Cncmitant drug therapy with certain drugs (see drug interactins abve) Frequency f bld tests in the abve situatins shuld be agreed between the Specialist and the GP. NB: Urgent FBC shuld be prcessed if the patient cmplains f intercurrent illness. Actin t be taken by GP in event f abnrmal bld test results r if patient experiences certain symptms / adverse events Refer t tables 1) and 2) at end f this dcument fr actin t be taken by GP Prescribing A prescriptin shuld nly be issued if recent bld tests have been dne and the results are within acceptable limits. GP shuld ensure that a rbust system is in place t deal with repeat prescriptins as azathiprine is a high risk drug that requires regular bld test mnitring. Ensure that an apprpriate quantity f tablets are issued (usually nly sufficient t last until the next bld test will be reprted and Page 5 f 8
the next prescriptin issued). When t refer back t Specialist: Reprt t and seek advice n any abnrmal bld test results (see table 1 belw). Reprt t and seek advice if patient experiences any f the symptms / adverse events listed in table 2 belw. Seek advice if cnsidering starting a patient n allpurinl, (xipurinl r thipurinl*) therapy (due t severity f interactin). Reprt t and seek advice n any aspect f patient care that is f cncern t the GP and may affect treatment. Refer all pregnant patients/ patients wh wish t breastfeed and patients cnsidering pregnancy. Refer any patient wh des nt cmply with bld test mnitring. Hw ften will the patient be reviewed by the specialist? Frequency will vary between individual patients. Regardless f disease severity, ALL patients shuld be reviewed at least annually by the Specialist. Cmmunicatin The dsage regimen and the required frequency f bld test mnitring shuld be clearly explained t the patient. Results f bld tests taken by the Specialist will be recrded in the hspital recrds and the results can be accessed by the GP via the ICE system. (If the GP cannt access bld test results via ICE, then it shuld be agreed that the Specialist will send a paper cpy f the bld test results t the GP in a timely manner.) Any dsage adjustments made by the Specialist will be recrded in the hspital medical recrds and full details sent t the GP. GP s shuld cntact the Specialist fr advice if any dse adjustments are required r if the need t stp the drug arises. GP t seek advice frm Specialist in the event f an abnrmal bld test r if patient experiences any f the symptms / adverse events as highlighted in table 2. Patient shuld be tld t infrm the prescribing clinician immediately if any ral ulceratins, ulceratins f the thrat, recurrent sre thrats, fever, bruising, bleeding r ther signs f myelsuppressin ccur. Patient shuld be advised t reprt any ther side effects t the prescribing clinician Patient shuld be advised t reprt any suspected pregnancy t the GP and / r Specialist. Patient shuld be advised t avid excessive sun expsure and t use sunscreens and prtective clthing. Patients wh have nt had expsure t Varicella-zster, shuld be advised t avid cntact with peple wh have active chickenpx r shingles and reprt any such cntact urgently t their GP r Specialist. Page 6 f 8
Table 1) ACTION TO BE TAKEN BY GP if the fllwing ccurs:- White Bld Cells < 3.5 x 10 9 /l Discuss with Specialist White Bld Cells < 2.5 x 10 9 /l Stp azathiprine and discuss with Specialist Neutrphils 1.5 2 x 10 9 /l Discuss with Specialist Neutrphils < 1.5 x 10 9 /l Stp azathiprine and discuss with Specialist Platelets < 150 x 10 9 /l Stp azathiprine and discuss with Specialist Hb If haemglbin is lw, haematinics shuld be checked and discussed with the specialist ALP > 250 IU /l ALT >100 IU / l Stp azathiprine and discuss with Specialist Significant reductin in renal functin Stp azathiprine and discuss with Specialist MCV > 105 fl Check TSH, B12, Flate If B12, flate lw, start apprpriate supplementatin PLEASE NOTE THAT IN ADDITION TO ABSOLUTE VALUES FOR HAEMATOLOGICAL INDICES, A RAPID FALL OR RISE, OR A CONSISTENT UPWARD OR DOWNWARD TREND IN ANY VALUE SHOULD PROMPT CAUTION AND EXTRA VIGILANCE. Table 2 Symptms / Adverse events Rash (significant and new) Abnrmal bruising r bleeding Oral ulceratins, ulceratins f the thrat,, recurrent sre thrats, infectins, fever, chills Any ther signs f myelsuppressin Cntact Specialist fr advice. If cncerned, stp azathiprine and check FBC Check FBC and cntact Specialist fr advice Check FBC and cntact Specialist fr advice. NB If severe, stp azathiprine and discuss with Specialist Check FBC and cntact Specialist fr advice Severe abdminal pain Stp treatment and cnsider Page 7 f 8
pancreatitis. Check amylase and cntact Specialist fr advice. Nausea and /r vmiting Persistent /wrsening diarrhea Hair lss Advice t take drug at night. If persists, advise patient t divide dse and take with fd. If n imprvement, discuss a pssible dse reductin with Specialist. Cntact Specialist fr advice. Mild cnsider dse reductin n advice f the Specialist. If severe, stp azathiprine and discuss with Specialist. IF IN ANY DOUBT ABOUT ANY ASPECT OF PRESCRIBING AZATHIOPRINE and /r BLOOD TEST MONITORING ETC, PLEASE CONTACT THE GASTROENTEROLOGY TEAM: The Lutn and Dunstable Hspital Cnsultants Cntact Number: 01582 497478. Nurse Specialist : 01582 718368 Page 8 f 8