Conventional Synthetic DMARDs (csDMARDs)

Administration: Oral

Dose:

• TPMT status should be checked prior to starting treatment.
• Usual starting dose 1mg/kg/dy increasing to 2-3mg/kg/dy according to consultant.

Time to response: 6 weeks to 3 months

Indications:

• Systemic Lupus Erythematosis and Other Connective Tissue Diseases.
• Vasculitis.
• Rheumatoid Arthritis.

Cautions:

• Impaired liver function & moderate/severe renal impairment.

Monitoring:

• FBC, U&E, LFT every 2 weeks until dose stable for 6 weeks; monthly for 3 months; then every 3 months

Important drug interactions:

• ALLOPURINOL requires reduction to 25% of usual dose of azathioprine if co-prescribed.
• FEBUXOSTAT - possible increased risk of haematotoxicity.
• ACE inhibitors – may cause anaemia.
• WARFARIN SODIUM - anticoagulant effects inhibited. May need to increase dose.

Ensure:

• Sunlight exposure is reduced using sunscreens and protective clothing.
• Avoid live attenuated vaccines:
  • Patients can receive shingles vaccination if dose of azathioprine ≤ 3mg/kg/day.
• Pneumococcal vaccination and annual influenza vaccination.
• If patients are exposed to chickenpox or shingles please contact the rheumatology department for further advice.

In the event of:

• Rash/ mouth ulcers - stop AZATHIOPRINE.
• Nausea - try anti-emetic or reduction in dose.
• MCV >105 – check serum folate, B12 & TSH and monitor MCV.
• Abnormal bruising/severe sore throat – stop and check urgent FBC.
• Serious infection – stop AZATHIOPRINE and restart once infection treated.
• Pregnancy and breastfeeding - continue AZATHIOPRINE.

Stop AZATHIOPRINE if:

• WBC < 3.5 x10⁹/L
• ALT/AST > two times normal
• Neutrophils < 1.6 x 10⁹/l
• Platelets < 150 x 10⁹/l

Administration: Oral
Grapefruit (including grapefruit juice) must be avoided for 1 hour before or after taking CICLOSPORIN tablets as bioavailability is increased.

Dose: The starting dose is usually 2.5mg/kg/dy in 2 divided doses for 6 weeks and then may be increased by 25mg every 2-4 weeks until effective or the maximum dose of 4mg/kg/dy has been reached.

Time to response: 3 months

Indications: Rheumatoid Arthritis.

Cautions:

• Impaired liver function & moderate/severe renal impairment.
• Uncontrolled hypertension.
• Severe electrolyte imbalance.

Monitoring:

• FBC, LFT, U&E, BP, Glc  every 2 weeks until dose stable for 3 months; then monthly

Important drug interactions:

• DICLOFENAC - reduce dose by 50%.
• COLCHICINE - avoid.
• SIMVASTATIN - maximum dose 10mg/dy.
• Potassium Sparing Diuretics – risk of hyperkalaemia.
• DIGOXIN - may increase serum digoxin levels.

Ensure:

• Avoid live attenuated vaccines.
• Pneumococcal vaccination and annual influenza vaccination.
• If patients are exposed to chickenpox or shingles please contact the rheumatology department for further advice.

In the event of:

• Hypertension – If BP > 140/90 treat in line with SIGN 149 Guidelines. If BP remains uncontrolled stop.
• Significant rise in fasting lipids – stop.
• Abnormal bruising – stop CICLOSPORIN and check FBC.
• Infection – stop CICLOSPORIN and restart once infection treated.
• Pregnancy or breastfeeding - this drug is likely to be safe.

Stop CICLOSPORIN if:

• Creatinine ≥ 30% from baseline
• Potassium above reference range
• Platelets <150 x 10⁹/l
• ALT/AST/alk phos > 2 times normal

Administration: Oral
Avoid antacids within 4 hours of dose.

Dose:

• The usual dose is 200 to 400mg daily.
• The maximum dose is 6.5mg/kg/day.

Time to response: Up to 6 months

Indications:

• Rheumatoid Arthritis.
• Systemic Lupus Erythematosis.
• Juvenile Idiopathic Arthritis.

Contraindications: Pre-existing maculopathy

Cautions:

• Impaired liver function & moderate/severe renal impairment.
• In epilepsy may reduce threshold for convulsions.
• May exacerbate psoriasis.
• Macular changes may make monitoring difficult.

Monitoring:

• A baseline visual assessment will take place at the rheumatology clinic.
• All patients on HCQ are advised to have annual optometry assessment to assess for macular changes.
• Patients should be advised to report any visual disturbance.

Important drug interactions: Avoid using HCQ with AMIODARONE, MOXIFLOXACIN, QUININE and MEFLOQUINE.

In the event of:

• Rash - stop and contact rheumatology.
• GI disturbance – reduce dose or try anti-emetic.
• Visual impairment detected at baseline – refer to optician and if appropriate to an ophthalmologist.
• Blurred vision in first few weeks of treatment – usually settles.
• Development of blurred vision after first few weeks or changes in visual acuity – stop medication and refer as per visual impairment.
• Pregnancy and breastfeeding – continue hydroxychloroquine.

Administration: Oral

Dose: The dose is usually 10-20mg daily.

Time to response: 8 weeks to 6 months

Indications:

• Rheumatoid Arthritis.
• Psoriatic Arthritis.

Contraindications:

• Impaired liver function & moderate/severe renal impairment.
• Unexplained anaemia and cytopaenia.
• Severe unexplained hypoproteinaemia.
• Pregnancy and breastfeeding.

Monitoring:

• FBC, U&E, LFT, blood pressure, weight fortnightly until on stable dose for 6 weeks; then monthly for 3 months; then 12 weekly thereafter

Ensure:

• Adequate contraception whilst taking LEFLUNOMIDE and for 2 years after stopping it. If patients wish to become pregnant rapid removal of its metabolite can be carried out using a washout procedure.
• If on WARFARIN - monitor INR closely whilst on LEFLUNOMIDE and for a few weeks after stopping it.
• Avoid live attenuated vaccines.
• Pneumococcal vaccination and annual influenza vaccination.
• If patients are exposed to chickenpox or shingles please contact the rheumatology department for further advice.

In the event of:

• Rash or itch – reduce dose +/- antihistamines; if severe stop.
• GI upset – give symptomatic treatment +/- dose reduction.
• Unexplained dyspnoea - stop LEFLUNOMIDE; arrange CXR.
• Hypertension – if BP > 140/90 treat in line with SIGN 149 Guidelines. If BP remains uncontrolled stop.
• Weight loss >10% with no other cause identified - reduce dose or stop.
• Headache or hair loss – reduce dose or stop.

Stop LEFLUNOMIDE if:

• WBC < 3.5 x10⁹/L
• ALT/AST > two times normal
• Neutrophils < 2.0 x 10⁹/l
• Platelets < 150 x 10⁹/l

It is advised that a two-month supply of MTX is issued on acute prescribing or on a repeat script to be issued twice only with 'force reauthorise' applied so that MTX can’t be reissued without bloods being taken. The day of the week on which methotrexate is taken should be stated.

Administration: Oral (2.5mg tablets only) or subcutaneously

Dose: The initial dose is 5-10mg once weekly increasing by 2.5-5mg every 2-6 weeks, until disease stabilised, up to a maximum dose of 25mg/week. Give 5mg of folic acid on every day of the week other than MTX day.

Time to response: 6 to 12 weeks

Indications:

• Rheumatoid Arthritis.
• Psoriatic Arthritis.
• Juvenile Idiopathic Arthritis.
• Systemic Lupus Erythematosis and other Connective Tissue Diseases.
• Peripheral Spondyloarthropathies.
• Vasculitis

Contraindications:

• Pregnancy and breast feeding, or planned pregnancy.
• Unexplained anaemia and cytopenia.
• Impaired liver function & moderate/severe renal impairment.
• Poor respiratory reserve (consider baseline PFTs).

Monitoring:

• FBC, U&E/Urinalysis, LFT weekly until dose of MTX and monitoring stable for 6 weeks; every 2-3 months thereafter

Ensure:

• Adequate contraception whilst on and for 3 months after stopping MTX.
• Patients stay well within recommended limits for alcohol consumption.
• TRIMETHOPRIM, CO-TRIMOXAZOLE, THEOPHYLLINE and PHENYTOIN are not co-prescribed.
• Avoid live attenuated vaccines:
  • Patients can receive shingles vaccination if on MTX ≤ 25mg per week.
• Pneumococcal vaccination if not administered in last 5 years and annual influenza vaccination.
• If patients are exposed to chickenpox or shingles please contact the rheumatology department for further advice.
• Pregnant women should not handle subcutaneous METHOTREXATE.

In the event of:

• Nausea – try anti-emetic or reduction in dose.
• Severe sore throat or abnormal bruising – stop & check urgent FBC.
• Unexplained dyspnoea or dry cough – stop MTX & arrange CXR.
• MCV > 105 – check B12, folate & TFTs and monitor MCV.
• Serious infection/dehydration – stop MTX & restart once treat.

Stop METHOTREXATE if:

• WBC < 3.5 x10⁹/L
• ALT/AST > two times normal
• Unexplained fall in albumin
• Mild to moderate renal impairment
• Neutrophils < 2.0 x 10⁹/l
• Platelets < 150 x 10⁹/l

Administration: Oral (usually 250mg tablets)

Dose:

• Usual starting dose is 500mg daily for first week, 500mg twice daily for second week, increasing by 500mg each week until on optimal dose.
• The maximum dose is 3g daily.

Time to response: 6 weeks to 3 months

Indications:

• Systemic Lupus Erythematosis and Other Connective Tissue Diseases.
• Vasculitis.

Contraindications:

• Pregnancy and breastfeeding.
• Localised or systemic infections.

Monitoring (Please enter results on the monitoring card.):

• FBC, U&E, LFT every 2 weeks until on stable dose for 6 weeks; monthly for 3 months; 12 weekly thereafter

Important drug interactions:

• CLOZAPINE - increased risk of agranulocytosis.
• Antacids, iron and COLESTYRAMINE reduce the absorption of MMF.

Ensure:

• Adequate contraception whilst taking MYCOPHENOLATE and for 6 weeks after stopping it.
• Avoid live attenuated vaccines.
• Pneumococcal vaccination and annual influenza vaccination.
• If patients are exposed to chickenpox or shingles please contact the rheumatology department for further advice.

In the event of:

• Mouth ulcers - try mouth wash. If severe stop MYCOPHENOLATE.
• Nausea - try anti-emetic or reduction in dose.
• Dyspepsia - try a PPI or reduce dose.
• Infection – stop MMF until the infection has been treated. The dose may need to be reduced.

Stop MYCOPHENOLATE if:

• WBC < 3.5 x10⁹/L
• ALT/AST > two times normal
• Neutrophils < 2.0 x 10⁹/l
• Platelets < 150 x 10⁹/l
• Declining renal function i.e. creatinine increasing > 1.5 fold

Administration: Oral.
Should be taken at least 30 minutes before food.
Patients should avoid taking iron tablets, indigestion remedies or calcium at the same time as PENICILLAMINE – neither will be absorbed.

Dose: Start at 125mg daily and increase 4 weekly to target dose (usually 500mg, although dose can be increased to 1g if required to achieve a response).

Time to response: 3 to 6 months

Indications: Rheumatoid Arthritis.

Contraindications:

• Pregnancy and breastfeeding.
• Moderate/severe renal impairment.
• Systemic lupus erythematosus

Monitoring (Please enter results on the monitoring card.):

• FBC, U&E, LFT every 2 weeks until on stable dose for 6 weeks; monthly for 3 months; 12 weekly thereafter
• Rash/mouth ulcers - ask about these at each visit.

In the event of:

• Severe rash or mouth ulcers – stop PENICILLAMINE (late rashes are more serious than early ones).
• Abnormal bruising/ severe sore throat – stop and check urgent FBC.
• Nausea - taking PENICILLAMINE before bed may help. May also respond to stemetil.
• Alteration of taste – continue treatment as this will resolve in most cases.

Stop PENICILLAMINE if:

• WBC < 3.5 x10⁹/L
• ALT/AST > two times normal
• Neutrophils < 2.0 x 10⁹/l
• Platelets < 150 x 10⁹/l
• Proteinuria is 2+ or more – check MSSU; if infection present treat this; if sterile stop PENICILLAMINE and quantify proteinuria.

Administration: Oral.

Dose:

• Start at 500mg daily and increase on a weekly basis by 500mg daily until a target dose of 40mg/kg is reached.
• The usual maximum daily dose is 4g.

Time to response: Minimum 3 months

Indications:

• Rheumatoid Arthritis.
• Psoriatic Arthritis.
• Juvenile Idiopathic Arthritis.

Contraindications:

• Allergy to CO-TRIMOXAZOLE/sulphonamides or ASPIRIN.
• History of exfoliative dermatitis.
• Severe renal failure.

Cautions:

• Impaired liver function & moderate renal impairment.
• Unexplained anaemia and cytopenia.

Monitoring (Please enter results on the monitoring card.):

• FBC, LFT every 2 weeks until on stable dose for 6 weeks; monthly for 3 months; 12 weekly up until 1 year, after 1 year no monitoring is required.

Ensure:

• Male patients are aware that it can cause transient reversible oligospermia.
• Pregnant patients on SULFASALAZINE take FOLIC ACID 5mg daily.

In the event of:

• Mouth ulcers – stop SULFASALAZINE.
• Abnormal bruising/severe sore throat – stop and check urgent FBC.
• Nausea/dizziness/headache – if possible continue. May have to reduce dose or stop if symptoms severe.
• Unexplained acute widespread rash – stop SULFASALAZINE and seek urgent specialist (dermatological) advice.
• MCV >105 – check serum folate, B12 & TSH and monitor MCV.

Stop SULFASALAZINE if:

• WBC < 3.5 x10⁹/L
• ALT/AST > two times normal
• Neutrophils < 2.0 x 10⁹/l
• Platelets < 150 x 10⁹/l