What drug class is methotrexate?
Antimetabolites
What;s the MoA for methotrexate?
Anti-folate - it inhibits the conversion of dihydrofolate (folic acid) to tetrahydrofolate needed to make purines and pyrimidines and therefore DNA; prevents cellular replication
What are its uses?
RA
Cancer
Psoriasis
Crohn’s Disease
What’s its dose?
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
What are the possible regimens for MTX and folic acid?
- 5mg OW on the day after MTX day
- 5mg OD except for MTX day
- 1mg OD except MTX day
What happens if you miss a dose?
More than 3 days take next scheduled dose on normal day
What are some counselling points to the patient?
- 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.
What are the SE’s of MTX?
- blood dyscrasias
- hepatotoxicity
- nephrotoxicity
- pulmonary toxicity
- GI toxicity
- MTX-induced SE’s/toxicity = folinic acid rescue
BLOOD DYSCRASIAS
- 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.
HEPATOTOXICITY
Pt counselling => report N/V, dark urine, jaundice, abdominal pain (upper right), pruritus, malaise, pale-coloured stools
Long term use can cause hepatic cirrhosis
NEPHROTOXICITY
MTX is renally excreted
PULMONARY TOXICITY
Pt counselling => report shortness of breath, cough and fever
Long term use can cause pulmonary fibrosis
GI TOXICITY
Pt counselling => report stomatitis (inflamed and sore mouth); first sign of GI toxicity
Conception and pregnancy?
TERATOGENIC.
Effective contraception during and 6 months after, both men and women
Handling?
- avoid skin contact with cytotoxic drugs
- pregnant women should avoid handling at all
Interactions?
- 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
Pre-treatment screening?
Exclude pregnancy prior to beginning and FBC, renal and LFT tests before beginning
Monitoring?
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
