Users

Methotrexate Monitoring

Affected Drug

• L01BA01 Methotrexate

Baseline

Baseline: CBC, SCr, ALT, AST, alk phos, albumin, bilirubin, INR/PTT. CXR. Hep B/C serology in high risk patients. Ensure appropriate contraception for female patients of child bearing age.

Follow-up

Follow-up: Q4-8 weeks: CBC, AST, SCr, albumin. Ensure appropriate ongoing contraception. Ensure appropriate folic acid supplementation (1 mg daily or 7 mg once weekly).

Important Interactions

• Drugs: alcohol
  Interaction avoid to decrease liver toxicity
• Drugs: NSAIDS
  Interaction May increase MTX related toxicity (avoid if possible)
• Drugs: penicillins
  Interaction May increase MTX related toxicity due to ↓ renal elimination (primarily with high dose MTX ≥20mg/wk)
• Drugs: TMP/SMX
  Interaction May increase MTX related toxicity due to ↓ renal elimination and folate antagonism (TMP)

Details

Conditions	System	Monitoring		ADE	Incidence	Recommendation
		Baseline	Follow-up
	hematol	CBC	CBC q4-8 weeks	myelosuppression	Dose related	↓ dose or D/C if severe; ensure folate supplementation
	Hepatic	ALT/AST, alk phos, albumin, HepB/C serology (if high risk)	CBC, AST, albumin Q4-8 weeks	elevated serum transaminases	10-15%	↓ dose or D/C if severe
				hepatitis	rare	↓ dose or D/C if severe
	Resp	Hx/Px, CXR	Hx/Px, CXR & PFT’s if symptoms	pulmonary infiltrates/pneumonitis	1%	D/C med
	GI	Hx/Px	Hx/Px	gi upset, stomatitis	20-30%	Self-limited, decreased incidence with folic acid 1 mg/d or 7 mg/week
	Renal	SCr	SCr q4-8 weeks	need to decrease mtx dose if changing renal fxn to prevent toxicity; renal failure (rare	N/A	eGFR 50-80 ↓dose by 20-30% ; eGFR 10-50 ↓ 50%; eGFR <10 - avoid
	Reproductive	Negative pregnancy test		spontaneous abortion		All female patients in child bearing years need to employ 1, preferably 2, reliable methods of contraception; D/C 3 mo prior to attempting pregnancy
				severe life threatening malformations		All female patients in child bearing years need to employ 1, preferably 2, reliable methods of contraception; D/C 3 mo prior to attempting pregnancy

References

• American College Of Rheumatology Ad Hoc Committee On Clinical Guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis and Rheumatism. 1996; 39:723-31
• Ortiz Z, Shea B, Suarez-Almazor ME et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. The Cochrane Collaboration. 2009
• Simon, CH, Dijkamans BA, Bernelot Moens, HJ et al. Laboratory Screening for side effects of disease modifying antirheumatic drugs in daily rheumatological practice. Scandinavian Journal of Rheumatology. 1998; 27:170-9
• Kremer, J. Use of methotrexate in treatment of rheumatoid arthritis. In: UpToDate, Basow, DS (Ed) UpToDate, Waltham, MA, 2010
• Kremer, J. Major side-effects of low dose methotrexate. In: UpToDate, Basow, DS (Ed) UpToDate, Waltham, MA, 2010
• Gray J, editor. Therapeutic Choices, 5th edition. Ottawa: The Canadian Pharmacists Association; 2007