Methotrexate Flashcards
MoA of MTX
Inhibits the enzyme dihydrofolate reductase which is essential for the synthesis of purines and pyrimidines
Indications of MTX: Crohn’s disease
- Mild to moderate CD that is refractory or intolerant to thiopruines under expert supervision only
- Severe CD under expert supervision (unlicensed)
- Maintenance of remission of severe CD under expert supervision
Indications of MTX: RA
- Moderate to severe active RA under expert supervision
- Severe active RA under expert supervision
Indications of MTX: neoplastic diseases
Neoplastic disease = disorders that cause abnormal growth of tissue (tumours) which can be benign or malignant
Specialist use only
Indications of MTX: psoriasis
Severe psoriasis unresponsive to conventional therapy under expert supervision
Important safety information regarding MTX - dose for non-malignancy
- Pt given MTX by any route for non-cancer treatment should NOT be given more than their intended weekly dose
- Dose is always weekly!
How to avoid error with low-dose MTX
- Pt or carer is advised of their dose, freq, reason for taking MTX and any other prescribed medication (e.g. folic acid)
- Only one strength of MTX tablet prescribed and dispensed (usually 2.5mg)
- Rx and dispensing label clearly shows the dose and freq of MTX administration
- Pt/carer to report ASAP onset of any features of blood disorders, liver toxicity, respiratory effects
State some signs that pt/carer should report immediately
- Blood disorder: sore throat, bruising, mouth ulcers
- Liver toxicity: dark urine, n+v, abdominal discomfort
- Respiratory effects: SOB
MHRA advice regarding dosage for autoimmune conditions
- With oral use, MTX should be taken ONCE weekly in autoimmune conditions (less commonly, in some cancer therapy regimens)
- Inadvertent overdose due to more frequent dosing (including daily dosing) has resulted in some fatalities
Measures for prescribers to reduce risk of fatal overdose due to inadvertent daily dosage instead of weekly dosage
- Ensure pt can understand & comply with once weekly dosage before prescribing
- Decide which day of the week to take it and write this on Rx
- Consider pt overall polypharmacy burden when deicing which formulation to prescribe, esp for those with high pill burden
- Inform pt and carers of potentially fatal risk of accidental overdose fi MTX is taken more than once weekly
- Advise them to seek immediate medical attention if overdose is suspected
MHRA advise to pharmacy staff & patients regarding MTX tablets
- Dispensers to remind pt of once weekly dosing and risk of potentially fatal overdose if they take more than directed
- Write day of week for dosage in the space on the outer package where possible
- Encourage patients to write the day of the week for dosage in their patient alert card and always carry it with them
MHRA advice - photosensitivity reactions
- Photosensitivity reactions including phototoxicity are known SE
- May occur with low and high dose treatment
- Reactions are distinct from radiation recall reactions
- Can appear as severe sunburn (e.g. rashes with papules or blistering, sometimes swelling)
- Rarely photosensitivity reactions have contributed to deaths from secondary infections
HCP role in counselling patients of the risk of photosensitivity reactions
- HCP should inform pt and carers of the risk and signs of photosensitivity reactions during MTX treatment and advice them to
○ Avoid exposure to UV light (including intense sunlight esp between 11-3pm, sunlamps, sunbeds)
○ Use sun cream with high SPF and wear protective clothing during sun exposure
○ Speak to HCP if any concerns about skin reaction
MTX is contraindicated in:
- Active infection
- Ascites
- Immunodeficiency syndromes
- Significant pleural effusion
Use MTX with caution in the following
- Dehydration – increased risk of toxicity
- Diarrhoea
- Extreme caution in blood disorders – avoid if severe
- Peptic ulceration – avoid in active disease
- Photosensitivity
- Risk of accumulation in pleural effusion or ascites - drain before treatment
- Ulcerative colitis
- Ulcerative stomatitis
Why do you need to be cautious of blood count when using MTX
- bone marrow suppression can occur abruptly
- factors likely to increase toxicity include advanced age, renal impairment, concomitant use with another anti-folate drug (e.g. trimethoprim)
- a clinically significant drop in WBC count or platelet count needs immediate withdrawal of MTX and introduction of supportive therapy
Cautions - GI toxicity
- Withdraw if stomatitis or diarrhoea develops
- May be first sign of GI toxicity
Cautions - photosensitivity
Psoriasis lesions may be aggravated by UV radiation - report of skin ulcerations
Radiation recall reaction has been reported in both radiation and sun-damaged skin
Cautions - liver toxicity
- Liver cirrhosis reported
- Do not start treatment or discontinue if any abnormality of liver function or liver biopsy is present or develops during therapy
- Abnormalities can return to normal within 2 weeks after which treatment may be recommended if judged appropriate
- Persistent increases in liver transaminases may necessitate dose reduction or discontinuation
Cautions - pulmonary toxicity
- May be a special problem in RA
- Manufacturer advised patients to seek medical attention if dyspnoea, cough or fever develops
- Monitor for symptoms at each visit
- Discontinue if pneumonitis suspected
Why is folic acid often prescribed with MTX
- Given to reduce side effects
- Decreases mucosal and GI SE of MTC and may prevent hepatotoxicity
- No evidence of reduction in haematological SE
- Withdraw if ulcerative stomatitis – may be first sign of GI toxicity
- Treatment with folinic acid as calcium folinate may be required in acute toxicity
Conception and contraception
Effective contraception needed during and for at least 6 months after treatment in both M and F
Use of MTX in pregnancy
Avoid - teratogenic
Fertility may be reduced during therapy but this may be reversible
Use of MTX whilst BF
Do not BF; present in milk
Use of MTX in hepatic impairment
- When used for malignancy, avoid in severe hepatic impairment & consult local treatment protocol for details
- Avoid with hepatic impairment for non-malignant conditions - dose related toxicity
Use of MTX in renal impairment
Risk of nephrotoxicity with high doses
Use with caution
Reduce dose - consult product literature
Avoid in severe impairment
Pre-treating screening
- Exclude pregnancy before treatment
- FBC and renal and liver function test needed before starting treatment
Due to reports of blood dyscrasias (including fatalities) and liver cirrhosis with low dose MTX, the following monitoring requirements:
○ Have FBC and R&LFTs repeated every 1-2 weeks until therapy stabilised
○ Thereafter every 2-3 months
○ Report all symptoms and signs suggestive of infection, esp sore throat
○ Local protocols for freq of monitoring may vary
○ Acute toxicity: may need treatment with folinic acid (as calcium folinate)
Why might folonic acid be prescribed following MTX administration
Helps prevent MTX-induced mucositis and myelosuppression
Patient and carer advice
- Immediately report onset of any features of blood disorders (sore throat, bruising, mouth ulcers, liver toxicity (n+v, abdominal discomfort, dark urine), respiratory effects (SOB)
- Avoid exposure to UV light (e.g. intense sunlight, sunlamps, sunned) - risk of photosensitivity reactions
- Avoid self-medication with OTC aspirin or ibuprofren
- Counsel pt on the dose, treatment booklet, and use of NSAIDs
- For once weekly oral use, provide patient alert cart
Does alcohol interact with MTX
Severe interaction
Alcohol induced liver disease increases risk of hepatotoxicity in those taking MTX
Do the penicillins interact with MTX
Yes - amoxicillin, ampicillin, flucloxacillin, phenoxymethylpenicillin, pivmecillinam etc
Severe interaction
Predicted to increase risk of toxicity when given with MTX - monitor
Can you take aspirin with MTX
High dose aspirin predicted to increase risk of toxicity when given with MTX
Severe interaction
Monitor!!
Can also increase risk of nephrotoxicity
Some vaccines should not be administered to patients taking MTX - why?
- Live vaccines e.g. BCG, cholera, dengue, herpes-zoster, MMR, rotavirus, typhoid, varicella-zoster, yellow fever
- They are predicted to increase the risk of generalised infection (possibly life-threatening) when given with high dose MTX
- Avoid! Severe. Refer to green book
Can NSAIDs be taken with MTX
- All NSAIDs are predicted to increase the risk of toxicity when given with MTX (esp high dose MTX)
- Monitor! Severe interaction
Does indometacin interact with MTX
Yes - it is an NSAID
Predicted to increase risk of toxicity when given with MTX (esp high dose)
Monitor; severe interaction
Does ketorolac interact with MTX
Yes - it is an NSAID
Predicted to increase risk of toxicity when given with MTX (esp high dose)
Monitor; severe interaction
Can dalteparin and enoxaparin be given with MTX
Severe interaction
MTX might increase risk of hepatotoxicity when given with high dose dalteparin/enoxaparin
Can PPIs be given alongside MTX
Severe interaction
Decreases clearance of MTX (high dose)
Use with caution or avoid!
Does levetiracetam interact with MTX
Yes, decreases clearance of MTX
Monitor BOTH drug concentrations
Severe interaction
Can nitrous oxide be given with MTX
Avoid
Severe interaction
Potentially increases risk of MTX toxicity
Which antibiotic increases the risk of haematological side effects when given with MTX so therefore should be avoided?
Trimethoprim
Does trimethoprim interact with MTX
Yes, severe
Avoid
Increases risk of haematological SE (sometimes fatal) when given with MTX
Also can increase risk of nephrotoxicity
Common or very common SE of MTX with oral use and parenteral use
Anaemia
Appetite reduced
Diarrhoea
Drowsiness
Fatigue
GI discomfort
Headache
Increased risk of infection
Leucopenia
N+V
Oral disorders
Respiratory disorders
Skin reactions
Throat ulcer
Thrombocytopenia
