Methotrexate

Question 1

What drug class is methotrexate?

Answer 1

Antimetabolites

Question 2

What;s the MoA for methotrexate?

Answer 2

Anti-folate - it inhibits the conversion of dihydrofolate (folic acid) to tetrahydrofolate needed to make purines and pyrimidines and therefore DNA; prevents cellular replication

Question 3

What are its uses?

Answer 3

RA
Cancer
Psoriasis
Crohn’s Disease

Question 4

What’s its dose?

Answer 4

OW on the same day each week
A prescription must have the DOSE and FREQUENCY (Xmg weekly) and prescribe only 1 strength.

Concomitant folic acid 5mg helps to reduce MTX SE’s

Question 5

What are the possible regimens for MTX and folic acid?

Answer 5

• 5mg OW on the day after MTX day
• 5mg OD except for MTX day
• 1mg OD except MTX day

Question 6

What happens if you miss a dose?

Answer 6

More than 3 days take next scheduled dose on normal day

Question 7

What are some counselling points to the patient?

Answer 7

• weekly dose and avoid OTC NSAIDS as it can increase the risk of toxicity
• Annual flu vaccination as MTX can cause immunosuppression
• Methotrexate treatment booklet which is given when first dispensed.

Question 8

What are the SE’s of MTX?

Answer 8

• blood dyscrasias
• hepatotoxicity
• nephrotoxicity
• pulmonary toxicity
• GI toxicity
• MTX-induced SE’s/toxicity = folinic acid rescue

Question 9

BLOOD DYSCRASIAS

Answer 9

• Low WBCs => susceptible to infection.
  pt counselling => report mouth ulcers, fever, malaise, sore throat
  The risk of neutropenia is increase when given with clozapine
• Low RBCs => anaemia
  pt counselling => report extreme tiredness, pallor, dizziness
• Low platelets => thrombocytopenia
  Pt counselling => report bruising and bleeding easily.

Question 10

HEPATOTOXICITY

Answer 10

Pt counselling => report N/V, dark urine, jaundice, abdominal pain (upper right), pruritus, malaise, pale-coloured stools
Long term use can cause hepatic cirrhosis

Question 11

NEPHROTOXICITY

Answer 11

MTX is renally excreted

Question 12

PULMONARY TOXICITY

Answer 12

Pt counselling => report shortness of breath, cough and fever
Long term use can cause pulmonary fibrosis

Question 13

GI TOXICITY

Answer 13

Pt counselling => report stomatitis (inflamed and sore mouth); first sign of GI toxicity

Question 14

Conception and pregnancy?

Answer 14

TERATOGENIC.

Effective contraception during and 6 months after, both men and women

Question 15

Handling?

Answer 15

• avoid skin contact with cytotoxic drugs

- pregnant women should avoid handling at all

Question 16

Interactions?

Answer 16

• Increased risk of blood disorders => phenytoin, trimethoprim/co-trimox (anti-folates), clozapine
• Reduced renal excretion = MTX toxicity => NSAIDs (vasoconstriction of afferent renal arteriole) and penicillins
• Increased risk of hepatotoxicity => Isotretinoin, rifampicin, ketoconazole, phenothiazine antipsychotics
• Increased risk of toxicity => cipro, doxycycline, tetracycline, sulfonamides, ciclosporin, PPI, leflunomide

Question 17

Pre-treatment screening?

Answer 17

Exclude pregnancy prior to beginning and FBC, renal and LFT tests before beginning

Question 18

Monitoring?

Answer 18

FBC, renal and LFT are repeated every 1 - 2 weeks until therapy stabilised, thereafter pts should be monitored every 2 - 3 months.

Report symptoms of infection, esp sore throat