Common use of Specialist Nurse Clause in Contracts

Specialist Nurse. Indication Methotrexate is used in the treatment of adults with severe, active, classical or definite rheumatoid arthritis who are unresponsive or intolerant to conventional therapy and psoriatic arthritis (unlicensed) Dosage and Administration Supply only 2.5 mg strength tablets, as it reduces the risk of accidental overdose (see Specialist Pharmacy Service website). Issue the methotrexate monitoring booklet to all patients. Update with any dose changes Please note: Oral methotrexate 10 mg strength is not recommended for use in the BSSE health economy. BSR recommendation Typical dose: 7.5–25 mg ONCE weekly; starting dose may vary depending on the severity of the condition and patient characteristics such as age, renal function and other comorbid conditions. The initial dose may be 5–10 mg once weekly, increasing by 2.5–5 mg every 2–6 weeks until disease stabilised. The maximum licensed dose in RA is 25 mg/week. Rarely, the maximum dose can be 30 mg/week. Lower doses should be considered for frail elderly patients who often have poor renal function. If maximum oral dose is not effective or causes intolerance, consider i.m. or subcutaneous route of administration before discontinuation of the drug. Suggested regimen Starting dose 7.5 mg – 10 mg per week for two weeks Titration Dependent on tolerability and blood picture: • 10 mg per week for four weeks • Then 12.5 mg per week for four weeks Subsequent dosing in increments 2.5 mg every two to four weeks depending on response Range 2.5 mg to 20 mg as a single dose taken on the same day once a week. Spreading the dose over 24 hours helps reduce the risk of nausea NB: Dose can be increased to a maximum of 25 mg per week under specialist guidance (unlicensed) Folic acid 5 mg once a week taken 24 hours after dose of MTX can help reduce some minor side effects By injection Subcutaneous self injection by patient or carer may be used - hospital protocol applies Renal Impairment Methotrexate is contraindicated in the presence of severe/significant renal or significant hepatic impairment. Hepatic impairment Contra-indications / Special precautions Contraindications • Patients with a known allergic hypersensitivity to methotrexate should not receive methotrexate. • severe/significant renal renal impairment. • significant hepatic impairment. Liver disease including fibrosis, cirrhosis, recent or active hepatitis; active infectious disease; and overt or laboratory evidence of immunodeficiency syndrome(s) • Serious cases of anaemia, leucopenia or thrombocytopenia. • Concomitant administration of folate antagonists such as trimethoprim, co-trimoxazole and nitrous oxide should be avoided. Hepatotoxic and nephrotoxic drugs should be avoided. Methotrexate is teratogenic and should not be given to women intending to conceive, during pregnancy or to mothers who are breast feeding. Cautions • Methotrexate should be used with extreme caution in patients with haematological depression, renal impairment, diarrhoea, and ulcerative disorders of the GI tract and psychiatric disorders • Hepatic toxicity has been observed, usually associated with chronic hepatic disease. The administration of low doses of methotrexate for prolonged periods may give rise, in particular, to hepatic toxicity. Liver function should be closely monitored • Renal lesions may develop if the urinary flow is impeded and urinary pH is low, especially if large doses have been administered. Renal function should be closely monitored before, during and after treatment. Reduce dose of methotrexate in patients with renal impairment SUPPORTING INFORMATION • Particular care and possible cessation of treatment are indicated if stomatitis or GI toxicity occurs as haemorrhagic enteritis and intestinal perforation may result. • Haematopoietic suppression caused by methotrexate may occur abruptly and with apparently safe dosages. Full blood counts should be closely monitored before, during and after treatment. • Malignant lymphomas may occur in patients receiving low dose methotrexate, in which case therapy must be discontinued • Methotrexate has some immunosuppressive activity and therefore the immunological response to concurrent vaccination may be decreased. In addition, concomitant use of a live vaccine could cause severe antigenic reaction • Patients with pleural effusions and ascites should be drained prior to initiation of methotrexate therapy or treatment should be withdrawn • In patients with pre-existing pleuropulmonary disease, as may occur as a manifestation of rheumatoid arthritis and other autoimmune connective tissue disorders, physicians should be alert to the potential for methotrexate induced adverse effects on the pulmonary system. Patients should be advised to contact their physicians immediately should they develop a cough or dyspnoea. • Methotrexate is extensively protein bound and may displace, or be displaced by, other acidic drugs. The concurrent administration of agents such as p-aminobenzoic acid, chloramphenicol, penicillines, ciprofloxacin, diphenylhydantoins, phenytoin, acidic anti-inflammatory agents, salicylates, sulphonamides, tetracyclines, thiazide diuretics, probenicid or sulfinpyrazone or oral hypoglycaemics will decrease the methotrexate transport function of renal tubules, thereby reducing excretion and almost certainly increasing methotrexate toxicity • Methotrexate dosage should be monitored if concomitant treatment with aspirin, ibuprofen or indometacin (NSAID's) is commenced, as concomitant use of NSAID's has been associated with fatal methotrexate toxicity • Vitamin preparations containing folic acid or its derivatives may alter response to methotrexate. • Following administration to a man or woman conception should be avoided by using an effective contraceptive method for at least 3 months after using methotrexate Side Effects Common Nausea (spreading the dose over 24 hours helps), mouth ulcers, diarrhoea, hair loss Less Common • Leucopenia • Thromobocytopoenia • Pneumonitis • Increased nodule formation • Malaise • Abnormal LFTs • Modest rise in MCV is common - check B12 and folate • Watch for adverse effects if changing NSAIDs or consider reducing • methotrexate dose temporarily Monitoring Pretreatment Assessment FBC, U&E, LFT and CXR (unless CXR done within the last 6 months). Pulmonary function tests should be considered in selected patients British Society Rheumatology (BSR) recommendations After commencing treatment FBC, U&E, LFT every 2 weeks until dose of methotrexate and monitoring stable for 6 weeks; thereafter monthly until the dose and disease is stable for 1 yr. Thereafter the monitoring may be reduced in frequency, based on clinical judgement with due consideration for risk factors including age, comorbidity, renal impairment, etc. when monthly monitoring is to continue. Disease monitoring Monthly FBC, creatinine/calculated GFR, ALT and/or AST and albumin for 3 months; thereafter, FBC, creatinine/calculated GFR, ALT and/or AST and albumin at least every 12 weeks. More frequent monitoring is appropriate in patients at higher risk of toxicity. Occasional ESR/CRP helps assessment Actions to be taken: WBC<3.5x109/l Withhold until discussed with specialist team. Neutrophils <1.6x109/x Xxxxxxx until discussed with specialist team Platelets <140x109/l Withold until discussed with specialist team AST, ALT > twice upper limit reference range Withold until discussed with specialist team Albumin-unexplained fall (in absence of active disease) Xxxxxxx until discussed with specialist team Rash or oral ulceration, nausea and vomiting, diarrhoea Withold until discussed with specialist team New or increasing dyspnoea or dry cough Withold until discussed with specialist team MCV>105 fl Withhold and check serum B12, Folate and TFT and discuss with specialist team if necessary. Mild to moderate renal impairment Withold until discussed with specialist team Severe sore throat, abnormal bruising Xxxxxxx until discussed with specialist team Immediate FBC and withhold until the result is available

Specialist Nurse. Indication Methotrexate is used in the treatment of adults with severe, active, classical or definite rheumatoid arthritis who are unresponsive or intolerant to conventional therapy and psoriatic arthritis (unlicensed) Dosage and Administration Supply only 2.5 mg strength tablets, as it reduces the risk of accidental overdose (see Specialist Pharmacy Service websiteNational Patient Safety Agency Web site ). Issue the methotrexate monitoring booklet to all patients. Update with any dose changes Please note: Oral methotrexate 10 mg strength is not recommended for use in the BSSE health economy. BSR recommendation Typical dose: 7.5–25 mg ONCE weekly; starting dose may vary depending on the severity of the condition and patient characteristics such as age, renal function and other comorbid conditions. The initial dose may be 5–10 mg once weekly, increasing by 2.5–5 mg every 2–6 weeks until disease stabilised. The maximum licensed dose in RA is 25 mg/week. Rarely, the maximum dose can be 30 mg/week. Lower doses should be considered for frail elderly patients who often have poor renal function. If maximum oral dose is not effective or causes intolerance, consider i.m. or subcutaneous route of administration before discontinuation of the drug. Suggested regimen Starting dose 7.5 mg – 10 mg per week for two weeks Titration Dependent on tolerability and blood picture: •  10 mg per week for four weeks •  Then 12.5 mg per week for four weeks Subsequent dosing in increments 2.5 mg every two to four weeks depending on response Range 2.5 mg to 20 mg as a single dose taken on the same day once a week. Spreading the dose over 24 hours helps reduce the risk of nausea NB: Dose can be increased to a maximum of 25 mg per week under specialist guidance (unlicensed) Folic acid 5 mg once a week taken 24 hours after dose of MTX can help reduce some minor side effects By injection Subcutaneous self injection by patient or carer may be used - hospital protocol applies Renal Impairment Methotrexate is contraindicated in the presence of severe/significant renal or significant hepatic impairment. Hepatic impairment Contra-indications / Special precautions Contraindications •  Patients with a known allergic hypersensitivity to methotrexate should not receive methotrexate. •  severe/significant renal renal impairment. •  significant hepatic impairment. Liver disease including fibrosis, cirrhosis, recent or active hepatitis; active infectious disease; and overt or laboratory evidence of immunodeficiency syndrome(s) •  Serious cases of anaemia, leucopenia or thrombocytopenia. •  Concomitant administration of folate antagonists such as trimethoprim, co-trimoxazole and nitrous oxide should be avoided. Hepatotoxic Hepatic and nephrotoxic drugs should be avoided. Methotrexate is teratogenic and should not be given to women intending to conceive, during pregnancy or to mothers who are breast feeding. Cautions •  Methotrexate should be used with extreme caution in patients with haematological depression, renal impairment, diarrhoea, and ulcerative disorders of the GI tract and psychiatric disorders •  Hepatic toxicity has been observed, usually associated with chronic hepatic disease. The administration of low doses of methotrexate for prolonged periods may give rise, in particular, to hepatic toxicity. Liver function should be closely monitored •  Renal lesions may develop if the urinary flow is impeded and urinary pH is low, especially if large doses have been administered. Renal function should be closely monitored before, during and after treatment. Reduce dose of methotrexate in patients with renal impairment SUPPORTING INFORMATION •  Particular care and possible cessation of treatment are indicated if stomatitis or GI toxicity occurs as haemorrhagic enteritis and intestinal perforation may result. •  Haematopoietic suppression caused by methotrexate may occur abruptly and with apparently safe dosages. Full blood counts should be closely monitored before, during and after treatment. •  Malignant lymphomas may occur in patients receiving low dose methotrexate, in which case therapy must be discontinued •  Methotrexate has some immunosuppressive activity and therefore the immunological response to concurrent vaccination may be decreased. In addition, concomitant use of a live vaccine could cause severe antigenic reaction •  Patients with pleural effusions and ascites should be drained prior to initiation of methotrexate therapy or treatment should be withdrawn • In patients with pre-existing pleuropulmonary disease, as may occur as a  Pleuropulmonary manifestation of rheumatoid arthritis and other autoimmune connective tissue disorders, physicians should be alert to the potential for methotrexate induced adverse effects on the pulmonary systemhas been reported in patients with rheumatoid arthritis. Patients should be advised to contact their physicians immediately should they develop a cough or dyspnoeadyspnoea  Lung manifestations of RA and other connective tissue disorders are recognised to occur. • In patients with RA, the physician should be specifically alerted to the potential for methotrexate induced adverse effects on the pulmonary system  Methotrexate is extensively protein bound and may displace, or be displaced by, other acidic drugs. The concurrent administration of agents such as p-aminobenzoic acid, chloramphenicol, penicillines, ciprofloxacin, diphenylhydantoins, phenytoin, acidic anti-inflammatory agents, salicylates, sulphonamides, tetracyclines, thiazide diuretics, probenicid or sulfinpyrazone or oral hypoglycaemics will decrease the methotrexate transport function of renal tubules, thereby reducing excretion and almost certainly increasing methotrexate toxicity •  Methotrexate dosage should be monitored if concomitant treatment with aspirin, ibuprofen or indometacin (NSAID's) is commenced, as concomitant use of NSAID's has been associated with fatal methotrexate toxicity •  Vitamin preparations containing folic acid or its derivatives may alter response to methotrexate. •  Following administration to a man or woman conception should be avoided by using an effective contraceptive method for at least 3 months after using methotrexate Side Effects Common Nausea (spreading the dose over 24 hours helps), mouth ulcers, diarrhoea, hair loss Less Common •  Leucopenia •  Thromobocytopoenia •  Pneumonitis •  Increased nodule formation •  Malaise •  Abnormal LFTs •  Modest rise in MCV is common - check B12 and folate •  Watch for adverse effects if changing NSAIDs or consider reducing •  methotrexate dose temporarily Monitoring BSR Recommendations Pretreatment Assessment FBC, U&E, LFT and CXR (unless CXR done within the last 6 months). Pulmonary function tests should be considered in selected patients British Society Rheumatology (BSR) recommendations After commencing treatment FBC, U&E, LFT every 2 weeks until dose of methotrexate and monitoring stable for 6 weeks; thereafter monthly until the dose and disease is stable for 1 yr. Thereafter the monitoring may be reduced in frequency, based on clinical judgement with due consideration for risk factors including age, comorbidity, renal impairment, etc. etc when monthly monitoring is to continue. Re: Serum pro-collagen III in patients with psoriatic arthritis Disease monitoring Monthly FBC, creatinine/calculated GFR, ALT and/or AST and albumin for 3 months; thereafter, FBC, creatinine/calculated GFR, ALT and/or AST and albumin at least every 12 weeks. More frequent monitoring is appropriate in patients at higher risk of toxicity. Occasional ESR/CRP helps assessment Actions to be taken: WBC<3.5x109/l Withhold until discussed with specialist team. Neutrophils <1.6x109Neutrophils<2.0x109/x Xxxxxxx l Withhold until discussed with specialist team Platelets <140x109team. Platelets<150x109/l Withold Withhold until discussed with specialist team team. AST, ALT > ALT>twice upper limit of reference range Withold Withhold until discussed with specialist team Albumin-unexplained fall (in absence of active disease) Xxxxxxx Withhold until discussed with specialist team team. Rash or oral ulceration, nausea and vomiting, diarrhoea Withold Withhold until discussed with specialist team team. New or increasing dyspnoea or dry cough Withold until discussed Withhold and discuss urgently with specialist team team. MCV>105 fl Withhold and check serum B12, Folate and TFT and discuss with specialist team if necessary. Mild to moderate renal impairment Withold Withhold until discussed with specialist team Severe sore throat, abnormal bruising Xxxxxxx until discussed with specialist team Immediate FBC and withhold until the result of FBC is available

Specialist Nurse. Indication Methotrexate is used in the treatment of adults with severe, active, classical or definite rheumatoid arthritis who are unresponsive or intolerant to conventional therapy and psoriatic arthritis (unlicensed) Dosage and Administration Supply only 2.5 mg strength tablets, as it reduces the risk of accidental overdose (see Specialist Pharmacy Service websiteNational Patient Safety Agency Web site ). Issue the methotrexate monitoring booklet to all patients. Update with any dose changes Please note: Oral methotrexate 10 mg strength is not recommended for use in the BSSE health economy. BSR recommendation Typical dose: 7.5–25 mg ONCE weekly; starting dose may vary depending on the severity of the condition and patient characteristics such as age, renal function and other comorbid conditions. The initial dose may be 5–10 mg once weekly, increasing by 2.5–5 mg every 2–6 weeks until disease stabilised. The maximum licensed dose in RA is 25 mg/week. Rarely, the maximum dose can be 30 mg/week. Lower doses should be considered for frail elderly patients who often have poor renal function. If maximum oral dose is not effective or causes intolerance, consider i.m. or subcutaneous route of administration before discontinuation of the drug. Suggested regimen Starting dose 7.5 mg – 10 mg per week for two weeks Titration Dependent on tolerability and blood picture: • 10 mg per week for four weeks • Then 12.5 mg per week for four weeks Subsequent dosing in increments 2.5 mg every two to four weeks depending on response Range 2.5 mg to 20 mg as a single dose taken on the same day once a week. Spreading the dose over 24 hours helps reduce the risk of nausea NB: Dose can be increased to a maximum of 25 mg per week under specialist guidance (unlicensed) Folic acid 5 mg once a week taken 24 hours after dose of MTX can help reduce some minor side effects By injection Subcutaneous self injection by patient or carer may be used - hospital protocol applies Renal Impairment Methotrexate is contraindicated in the presence of severe/significant renal or significant hepatic impairment. Hepatic impairment Contra-indications / Special precautions Contraindications • Patients with a known allergic hypersensitivity to methotrexate should not receive methotrexate. • severe/significant renal renal impairment. • significant hepatic impairment. Liver disease including fibrosis, cirrhosis, recent or active hepatitis; active infectious disease; and overt or laboratory evidence of immunodeficiency syndrome(s) • Serious cases of anaemia, leucopenia or thrombocytopenia. • Concomitant administration of folate antagonists such as trimethoprim, co-trimoxazole and nitrous oxide should be avoided. Hepatotoxic Hepatic and nephrotoxic drugs should be avoided. Methotrexate is teratogenic and should not be given to women intending to conceive, during pregnancy or to mothers who are breast feeding. Cautions • Methotrexate should be used with extreme caution in patients with haematological depression, renal impairment, diarrhoea, and ulcerative disorders of the GI tract and psychiatric disorders • Hepatic toxicity has been observed, usually associated with chronic hepatic disease. The administration of low doses of methotrexate for prolonged periods may give rise, in particular, to hepatic toxicity. Liver function should be closely monitored • Renal lesions may develop if the urinary flow is impeded and urinary pH is low, especially if large doses have been administered. Renal function should be closely monitored before, during and after treatment. Reduce dose of methotrexate in patients with renal impairment SUPPORTING INFORMATION • Particular care and possible cessation of treatment are indicated if stomatitis or GI toxicity occurs as haemorrhagic enteritis and intestinal perforation may result. • Haematopoietic suppression caused by methotrexate may occur abruptly and with apparently safe dosages. Full blood counts should be closely monitored before, during and after treatment. • Malignant lymphomas may occur in patients receiving low dose methotrexate, in which case therapy must be discontinued • Methotrexate has some immunosuppressive activity and therefore the immunological response to concurrent vaccination may be decreased. In addition, concomitant use of a live vaccine could cause severe antigenic reaction • Patients with pleural effusions and ascites should be drained prior to initiation of methotrexate therapy or treatment should be withdrawn • In patients with pre-existing pleuropulmonary disease, as may occur as a Pleuropulmonary manifestation of rheumatoid arthritis and other autoimmune connective tissue disorders, physicians should be alert to the potential for methotrexate induced adverse effects on the pulmonary systemhas been reported in patients with rheumatoid arthritis. Patients should be advised to contact their physicians immediately should they develop a cough or dyspnoeadyspnoea • Lung manifestations of RA and other connective tissue disorders are recognised to occur. In patients with RA, the physician should be specifically alerted to the potential for methotrexate induced adverse effects on the pulmonary system • Methotrexate is extensively protein bound and may displace, or be displaced by, other acidic drugs. The concurrent administration of agents such as p-aminobenzoic acid, chloramphenicol, penicillines, ciprofloxacin, diphenylhydantoins, phenytoin, acidic anti-inflammatory agents, salicylates, sulphonamides, tetracyclines, thiazide diuretics, probenicid or sulfinpyrazone or oral hypoglycaemics will decrease the methotrexate transport function of renal tubules, thereby reducing excretion and almost certainly increasing methotrexate toxicity • Methotrexate dosage should be monitored if concomitant treatment with aspirin, ibuprofen or indometacin (NSAID's) is commenced, as concomitant use of NSAID's has been associated with fatal methotrexate toxicity • Vitamin preparations containing folic acid or its derivatives may alter response to methotrexate. • Following administration to a man or woman conception should be avoided by using an effective contraceptive method for at least 3 months after using methotrexate Side Effects Common Nausea (spreading the dose over 24 hours helps), mouth ulcers, diarrhoea, hair loss Less Common • Leucopenia • Thromobocytopoenia • Pneumonitis • Increased nodule formation • Malaise • Abnormal LFTs • Modest rise in MCV is common - check B12 and folate • Watch for adverse effects if changing NSAIDs or consider reducing • methotrexate dose temporarily Monitoring BSR Recommendations Pretreatment Assessment FBC, U&E, LFT and CXR (unless CXR done within the last 6 months). Pulmonary function tests should be considered in selected patients British Society Rheumatology (BSR) recommendations After commencing treatment FBC, U&E, LFT every 2 weeks until dose of methotrexate and monitoring stable for 6 weeks; thereafter monthly until the dose and disease is stable for 1 yr. Thereafter the monitoring may be reduced in frequency, based on clinical judgement with due consideration for risk factors including age, comorbidity, renal impairment, etc. etc when monthly monitoring is to continue. Re: Serum pro-collagen III in patients with psoriatic arthritis Disease monitoring Monthly FBC, creatinine/calculated GFR, ALT and/or AST and albumin for 3 months; thereafter, FBC, creatinine/calculated GFR, ALT and/or AST and albumin at least every 12 weeks. More frequent monitoring is appropriate in patients at higher risk of toxicity. Occasional ESR/CRP helps assessment Actions to be taken: WBC<3.5x109/l Withhold until discussed with specialist team. Neutrophils <1.6x109Neutrophils<2.0x109/x Xxxxxxx l Withhold until discussed with specialist team Platelets <140x109team. Platelets<150x109/l Withold Withhold until discussed with specialist team team. AST, ALT > ALT>twice upper limit of reference range Withold Withhold until discussed with specialist team Albumin-unexplained fall (in absence of active disease) Xxxxxxx Withhold until discussed with specialist team team. Rash or oral ulceration, nausea and vomiting, diarrhoea Withold Withhold until discussed with specialist team team. New or increasing dyspnoea or dry cough Withold until discussed Withhold and discuss urgently with specialist team team. MCV>105 fl Withhold and check serum B12, Folate and TFT and discuss with specialist team if necessary. Mild to moderate renal impairment Withold Withhold until discussed with specialist team Severe sore throat, abnormal bruising Xxxxxxx until discussed with specialist team Immediate FBC and withhold until the result of FBC is available

Specialist Nurse. Indication Methotrexate is used in the treatment of adults with severe, active, classical or definite rheumatoid arthritis who are unresponsive or intolerant to conventional therapy and psoriatic arthritis (unlicensed) Dosage and Administration Supply only 2.5 mg strength tablets, as it reduces the risk of accidental overdose (see Specialist Pharmacy Service website). Issue the methotrexate monitoring booklet to all patients. Update with any dose changes Please note: Oral methotrexate 10 mg strength is not recommended for use in the BSSE health economy. BSR recommendation Typical dose: 7.5–25 mg ONCE weekly; starting dose may vary depending on the severity of the condition and patient characteristics such as age, renal function and other comorbid conditions. The initial dose may be 5–10 mg once weekly, increasing by 2.5–5 mg every 2–6 weeks until disease stabilised. The maximum licensed dose in RA is 25 mg/week. Rarely, the maximum dose can be 30 mg/week. Lower doses should be considered for frail elderly patients who often have poor renal function. If maximum oral dose is not effective or causes intolerance, consider i.m. or subcutaneous route of administration before discontinuation of the drug. Suggested regimen Starting dose 7.5 mg – 10 mg per week for two weeks Titration Dependent on tolerability and blood picture: • 10 mg per week for four weeks • Then 12.5 mg per week for four weeks Subsequent dosing in increments 2.5 mg every two to four weeks depending on response Range 2.5 mg to 20 mg as a single dose taken on the same day once a week. Spreading the dose over 24 hours helps reduce the risk of nausea NB: Dose can be increased to a maximum of 25 mg per week under specialist guidance (unlicensed) Folic acid 5 mg once a week taken 24 hours after dose of MTX can help reduce some minor side effects By injection Subcutaneous self injection by patient or carer may be used - hospital protocol applies Renal Impairment Methotrexate is contraindicated in the presence of severe/significant renal or significant hepatic impairment. Hepatic impairment Contra-indications / Special precautions Contraindications • Patients with a known allergic hypersensitivity to methotrexate should not receive methotrexate. • severe/significant renal renal impairment. • significant hepatic impairment. Liver disease including fibrosis, cirrhosis, recent or active hepatitis; active infectious disease; and overt or laboratory evidence of immunodeficiency syndrome(s) • Serious cases of anaemia, leucopenia or thrombocytopenia. • Concomitant administration of folate antagonists such as trimethoprim, co-trimoxazole and nitrous oxide should be avoided. Hepatotoxic and nephrotoxic drugs should be avoided. Methotrexate is teratogenic and should not be given to women intending to conceive, during pregnancy or to mothers who are breast feeding. Cautions • Methotrexate should be used with extreme caution in patients with haematological depression, renal impairment, diarrhoea, and ulcerative disorders of the GI tract and psychiatric disorders • Hepatic toxicity has been observed, usually associated with chronic hepatic disease. The administration of low doses of methotrexate for prolonged periods may give rise, in particular, to hepatic toxicity. Liver function should be closely monitored • Renal lesions may develop if the urinary flow is impeded and urinary pH is low, especially if large doses have been administered. Renal function should be closely monitored before, during and after treatment. Reduce dose of methotrexate in patients with renal impairment SUPPORTING INFORMATION • Particular care and possible cessation of treatment are indicated if stomatitis or GI toxicity occurs as haemorrhagic enteritis and intestinal perforation may result. • Haematopoietic suppression caused by methotrexate may occur abruptly and with apparently safe dosages. Full blood counts should be closely monitored before, during and after treatment. • Malignant lymphomas may occur in patients receiving low dose methotrexate, in which case therapy must be discontinued • Methotrexate has some immunosuppressive activity and therefore the immunological response to concurrent vaccination may be decreased. In addition, concomitant use of a live vaccine could cause severe antigenic reaction • Patients with pleural effusions and ascites should be drained prior to initiation of methotrexate therapy or treatment should be withdrawn • In patients with pre-existing pleuropulmonary disease, as may occur as a manifestation of rheumatoid arthritis and other autoimmune connective tissue disorders, physicians should be alert to the potential for methotrexate induced adverse effects on the pulmonary system. Patients should be advised to contact their physicians immediately should they develop a cough or dyspnoea. • Methotrexate is extensively protein bound and may displace, or be displaced by, other acidic drugs. The concurrent administration of agents such as p-aminobenzoic acid, chloramphenicol, penicillines, ciprofloxacin, diphenylhydantoins, phenytoin, acidic anti-inflammatory agents, salicylates, sulphonamides, tetracyclines, thiazide diuretics, probenicid or sulfinpyrazone or oral hypoglycaemics will decrease the methotrexate transport function of renal tubules, thereby reducing excretion and almost certainly increasing methotrexate toxicity • Methotrexate dosage should be monitored if concomitant treatment with aspirin, ibuprofen or indometacin (NSAID's) is commenced, as concomitant use of NSAID's has been associated with fatal methotrexate toxicity • Vitamin preparations containing folic acid or its derivatives may alter response to methotrexate. • Following administration to a man or woman conception should be avoided by using an effective contraceptive method for at least 3 months after using methotrexate Side Effects Common Nausea (spreading the dose over 24 hours helps), mouth ulcers, diarrhoea, hair loss Less Common • Leucopenia • Thromobocytopoenia • Pneumonitis • Increased nodule formation • Malaise • Abnormal LFTs • Modest rise in MCV is common - check B12 and folate • Watch for adverse effects if changing NSAIDs or consider reducing • methotrexate dose temporarily Monitoring Pretreatment Assessment FBC, U&E, LFT and CXR (unless CXR done within the last 6 months). Pulmonary function tests should be considered in selected patients British Society Rheumatology (BSR) recommendations After commencing treatment FBC, U&E, LFT every 2 weeks until dose of methotrexate and monitoring stable for 6 weeks; thereafter monthly until the dose and disease is stable for 1 yr. Thereafter the monitoring may be reduced in frequency, based on clinical judgement with due consideration for risk factors including age, comorbidity, renal impairment, etc. when monthly monitoring is to continue. Disease monitoring Monthly FBC, creatinine/calculated GFR, ALT and/or AST and albumin for 3 months; thereafter, FBC, creatinine/calculated GFR, ALT and/or AST and albumin at least every 12 weeks. More frequent monitoring is appropriate in patients at higher risk of toxicity. Occasional ESR/CRP helps assessment Actions to be taken: WBC<3.5x109/l Withhold until discussed with specialist team. Neutrophils <1.6x109/x Xxxxxxx l Withold until discussed with specialist team Platelets <140x109/l Withold until discussed with specialist team AST, ALT > twice upper limit reference range Withold until discussed with specialist team Albumin-unexplained fall (in absence of active disease) Xxxxxxx Withold until discussed with specialist team Rash or oral ulceration, nausea and vomiting, diarrhoea Withold until discussed with specialist team New or increasing dyspnoea or dry cough Withold until discussed with specialist team MCV>105 fl Withhold and check serum B12, Folate and TFT and discuss with specialist team if necessary. Mild to moderate renal impairment Withold until discussed with specialist team Severe sore throat, abnormal bruising Xxxxxxx Withold until discussed with specialist team Immediate FBC and withhold until the result is available