Module 3: Methotrexate

Question 1

Methotrexate is a DMARD, what does that stand for?

Answer 1

Disease-modifying anti-rheumatic drugs.

Question 2

What is methotrexate’s MOA?

Answer 2

Methotrexate is a folate antimetabolite that inhibits DNA synthesis, repair and cellular replication. Actively proliferative tissues are more susceptible to the effects of methotrexate.

Mechanism in tx of RA and polyarticular-course juvenille idiopathic arthritis is unknown, but may affect immune function. In psoriasis thought to target rapidly proliferating epithelial cells in the skin.

In Crohn disease - may have immune modulator and anti-inflammatory activity.

Question 3

What are common adverse effects of methotrexate?

Answer 3

GI: Diarrhea, nausea, vomiting

Hepatic: increased liver enzymes

Question 4

What are significant adverse effects of methotrexate?

Answer 4

Dermatologic toxicity

GI toxicity

Hematologic toxicity

Hepatotoxicity

Infection

Nephrotoxicity

Neurotoxicity

Pulmonary toxicity

Question 5

What are significant drug interactions with methotrexate?

Answer 5

NSAIDs
Co-trimoxazole, trimethoprim or other abx for bacterial infections
Diuretics
Epilepsy meds (phenytoin)
Theophylline
Omeprazole
Folic acid or vitamin supplements containing folic acid or folat

Question 6

What are monitoring parameters with methotrexate?

Answer 6

• derm toxicity
• hematologic toxicity
• infection
• evaluate pregnancy status prior to use

For RA:
- CBC with diff and platelets, serum creatinine and LFTs: at regular intervals
- chest xray (within 1 year prior to initiation), Hep B & C serology, TB testing for those at high risk for exposure
- Liver biopsy for abnormal baseline LFTs, hx of alcoholism or chronic hep Bor C.