Guideline 48 Annex 6

Management of Early Rheumatoid Arthritis
Annex 6

Awareness of and vigilance for drug interactions is important, but concern about drug interactions should not prevent the prescription of drugs that are needed to reduce joint damage in early RA. Much more morbidity will accrue from leaving RA untreated than will occur as a result of these interactions.

Drug interactions with NSAIDs

Drug	Effect of NSAID on drug	Principal mechanism*
Antihypertensives (ACE Inhibitors, Angiotensin II receptor antagonists)	Therapeutic effect decreased Hyperkalaemia and renal impairment increased	Sodium retention Interference with intrarenal prostaglandins
Warfarin	Therapeutic effect increased	Displaced protein binding Inhibition of drug metabolism
Sulphonylureas	Therapeutic effect increased	Displaced protein binding
Cyclosporin	Risk of nephrotoxicity increased
Methotrexate	Therapeutic effect increased	Reduced renal clearance
Digoxin	Therapeutic effect increased	Reduced renal clearance
Lithium	Therapeutic effect increased	Reduced renal clearance
Phenytoin	Therapeutic effect increased	Displaced protein binding

Risk of GI haemorrhage is increased in patients on warfarin or corticosteroids. Further interactions are listed in the British National Formulary, Appendix 1⁵⁸
* the mechanisms underlying drug interactions are complex

Drug interactions with DMARDs

Drug	Interacts with
Azathioprine	Allopurinol Co-trimoxazole, trimethoprim, rifampicin Possibly warfarin
Hydroxychloroquine	Amiodarone Antiepileptics Digoxin
Cyclosporin	Multiple drugs, grapefruit juice
D-penicillamine	Antacids, zinc, iron (including proprietary indigestion tablets or mixtures) N.B. should not be taken together
Sulphasalazine	Digoxin
Methotrexate	Aspirin/NSAIDs Co-trimoxazole, trimethoprim, phenytoin All antifolate drugs Cyclosporin
Leflunomide	Phenytoin Warfarin Tolbutamide Other hepatotoxic/haemotoxic drugs
Minocycline	Antacids, zinc, iron Cyclosporin

N.B. further interactions are listed in the British National Formulary, Appendix 1 ⁵⁸

Management of Early Rheumatoid Arthritis Annex 6

Management of Early Rheumatoid Arthritis
Annex 6