METHOTREXATE

Question 1

MOA

Answer 1

• Anti-folate
• Inhibits conversion of dihydrofolate (folic acid) to tetrahydrofolate.
• Tetrohydrofolate is needed to make purines/pyrimidines and therefore DNA

Question 2

Indications

Answer 2

RA
Cancer
Psoriasis
Crohns disease

Question 3

Methotrexate - dose + Rx

Answer 3

Once WEEKLY
- same day each week
Prescription requirements:
- Dose and frequency (e.g. Xmg weekly)
- One strength tablet only

Question 4

Methotrexate - coprescribing

Answer 4

• Methotrexate is commonly co-prescribed with folic acid
• Not to be taken on the same day as each other
  Helps reduce MTX side effects

Question 5

Folic acid - dose

Answer 5

Dose:
5 mg once weekly on diff day to MTX (BNF dose
5 mg OD except on MTX day
1 mg OD except on MTX day

Question 6

Methotrexate - missed dose

Answer 6

< 3 days = take ASAP
3 days = take next scheduled dose on usual day

Question 7

Methotrexate - patient counselling

Answer 7

Take full dose once a week
Avoid OTC NSAIDs (risk of toxicity)
Annual flu vaccination (MTX causes immunosuppresion)
MTX treatment book

Question 8

SE

Answer 8

1. Blood dyscrasias
   - Low WBC
   - Low RBC
   - Low platelets
2. Hepatotoxicity
3. Nephrotoxicity
4. Pulmonary toxicity
5. GI toxicity

Question 9

REPORT

Answer 9

Patients should be advised to immediately report any signs of blood disorder, liver toxicity and respiratory effects

Question 10

Blood dyscrasias - low WBC

Answer 10

Susceptible to infection
Report mouth ulcers, fever, malaise, sore throat

Question 11

Blood dyscrasias - low RBC

Answer 11

Anaemia
Report extreme tiredness, pallor, dizziness

Question 12

Methotrexate - blood disorders

Answer 12

Sore throat, bruising, and mouth ulcers

Question 13

Methotrexate - liver toxicity

Answer 13

Nausea, vomiting, abdominal discomfort, dark urine, jaundice, itchy skin

Question 14

Methotrexate - Pulmonary Toxicity

Answer 14

Shortness of breath and coughing, fever

Question 15

Methotrexate - Gastro-intestinal Toxicity

Answer 15

Stomatitis and diarrhoea

Question 16

Methotrexate - Toxicity Antidote

Answer 16

Folinic Acid (calcium folinate)

Question 17

Methotrexate - monitoring

Answer 17

Full Blood Count, Renal Function Test, Liver Function Tests:
Every 1-2 weeks until stable
Every 2-3 months thereafter

Question 18

Methotrexate - Pregnancy

Answer 18

Screen out pregnancy prior to treatment
Antifolate - harmful to foetus growth
Use effective contraception during treatment and for at least 6 months after for both men and women

Question 19

interactions

Answer 19

• Nephrotoxic drugs (MTX reduces renal function)
• NSAIDS: no over-the-counter ibuprofen
• Anti-folates: Trimethoprim and phenytoin
• Hepatotoxic drugs: Rifampicin, antifungals, etc
• Omeprazole / Esomeprazole
  Reduces clearance → increases toxicity

Question 20

handling

Answer 20

Avoid contact with skin
Pregnant women should avoid handling at all

Question 21

Interactions - increased risk of blood disorders

Answer 21

Phenytoin
Trimethoprim/co-trimoxazole
Clozapine (neutropenia)

Question 22

Interaction - NSAIDs

Answer 22

• NSAIDs cause vasoconstriction of afferent renal arteriole
• NSAIDs reduced renal excretion = MTX toxicity

Question 23

Interactions - Increased risk of hepatotoxicity

Answer 23

• Isotretinoin
• Phenothiazine antipsychotics
• Rifampicin
• Ketoconazole

Question 24

Methotrexate + omeprazole

Answer 24

decreases clearance of MTX
increased toxicity

Question 25

Trimethoprim + methotrexate

Answer 25

• folate antagonists
• reduction in folic acid = increase MTX SE
• increase the risk of nephrotoxicity

Question 26

Methotrexate + bleomycin

Answer 26

Agranulocytosis