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High risk drugs afsha > Methotrexate > Flashcards

Methotrexate Flashcards

1
Q

MoA of MTX

A

Inhibits the enzyme dihydrofolate reductase which is essential for the synthesis of purines and pyrimidines

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2
Q

Indications of MTX: Crohn’s disease

A
  • 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
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3
Q

Indications of MTX: RA

A
  • Moderate to severe active RA under expert supervision
  • Severe active RA under expert supervision
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4
Q

Indications of MTX: neoplastic diseases

A

Neoplastic disease = disorders that cause abnormal growth of tissue (tumours) which can be benign or malignant
Specialist use only

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5
Q

Indications of MTX: psoriasis

A

Severe psoriasis unresponsive to conventional therapy under expert supervision

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6
Q

Important safety information regarding MTX - dose for non-malignancy

A
  • Pt given MTX by any route for non-cancer treatment should NOT be given more than their intended weekly dose
  • Dose is always weekly!
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7
Q

How to avoid error with low-dose MTX

A
  • 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
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8
Q

State some signs that pt/carer should report immediately

A
  • Blood disorder: sore throat, bruising, mouth ulcers
  • Liver toxicity: dark urine, n+v, abdominal discomfort
  • Respiratory effects: SOB
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9
Q

MHRA advice regarding dosage for autoimmune conditions

A
  • 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
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10
Q

Measures for prescribers to reduce risk of fatal overdose due to inadvertent daily dosage instead of weekly dosage

A
  • 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
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11
Q

MHRA advise to pharmacy staff & patients regarding MTX tablets

A
  • 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
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12
Q

MHRA advice - photosensitivity reactions

A
  • 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
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13
Q

HCP role in counselling patients of the risk of photosensitivity reactions

A
  • 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
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14
Q

MTX is contraindicated in:

A
  • Active infection
  • Ascites
  • Immunodeficiency syndromes
  • Significant pleural effusion
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15
Q

Use MTX with caution in the following

A
  • 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
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16
Q

Why do you need to be cautious of blood count when using MTX

A
  • 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
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17
Q

Cautions - GI toxicity

A
  • Withdraw if stomatitis or diarrhoea develops
  • May be first sign of GI toxicity
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18
Q

Cautions - photosensitivity

A

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

19
Q

Cautions - liver toxicity

A
  • 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
20
Q

Cautions - pulmonary toxicity

A
  • 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
21
Q

Why is folic acid often prescribed with MTX

A
  • 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
22
Q

Conception and contraception

A

Effective contraception needed during and for at least 6 months after treatment in both M and F

23
Q

Use of MTX in pregnancy

A

Avoid - teratogenic
Fertility may be reduced during therapy but this may be reversible

24
Q

Use of MTX whilst BF

A

Do not BF; present in milk

25
Q

Use of MTX in hepatic impairment

A
  • 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
26
Q

Use of MTX in renal impairment

A

Risk of nephrotoxicity with high doses
Use with caution
Reduce dose - consult product literature
Avoid in severe impairment

27
Q

Pre-treating screening

A
  • Exclude pregnancy before treatment
  • FBC and renal and liver function test needed before starting treatment
28
Q

Due to reports of blood dyscrasias (including fatalities) and liver cirrhosis with low dose MTX, the following monitoring requirements:

A

○ 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)

29
Q

Why might folonic acid be prescribed following MTX administration

A

Helps prevent MTX-induced mucositis and myelosuppression

30
Q

Patient and carer advice

A
  • 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
31
Q

Does alcohol interact with MTX

A

Severe interaction
Alcohol induced liver disease increases risk of hepatotoxicity in those taking MTX

32
Q

Do the penicillins interact with MTX

A

Yes - amoxicillin, ampicillin, flucloxacillin, phenoxymethylpenicillin, pivmecillinam etc
Severe interaction
Predicted to increase risk of toxicity when given with MTX - monitor

33
Q

Can you take aspirin with MTX

A

High dose aspirin predicted to increase risk of toxicity when given with MTX
Severe interaction
Monitor!!
Can also increase risk of nephrotoxicity

34
Q

Some vaccines should not be administered to patients taking MTX - why?

A
  • 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
35
Q

Can NSAIDs be taken with MTX

A
  • All NSAIDs are predicted to increase the risk of toxicity when given with MTX (esp high dose MTX)
  • Monitor! Severe interaction
36
Q

Does indometacin interact with MTX

A

Yes - it is an NSAID
Predicted to increase risk of toxicity when given with MTX (esp high dose)
Monitor; severe interaction

37
Q

Does ketorolac interact with MTX

A

Yes - it is an NSAID
Predicted to increase risk of toxicity when given with MTX (esp high dose)
Monitor; severe interaction

38
Q

Can dalteparin and enoxaparin be given with MTX

A

Severe interaction
MTX might increase risk of hepatotoxicity when given with high dose dalteparin/enoxaparin

39
Q

Can PPIs be given alongside MTX

A

Severe interaction
Decreases clearance of MTX (high dose)
Use with caution or avoid!

40
Q

Does levetiracetam interact with MTX

A

Yes, decreases clearance of MTX
Monitor BOTH drug concentrations
Severe interaction

41
Q

Can nitrous oxide be given with MTX

A

Avoid
Severe interaction
Potentially increases risk of MTX toxicity

42
Q

Which antibiotic increases the risk of haematological side effects when given with MTX so therefore should be avoided?

A

Trimethoprim

43
Q

Does trimethoprim interact with MTX

A

Yes, severe
Avoid
Increases risk of haematological SE (sometimes fatal) when given with MTX
Also can increase risk of nephrotoxicity

44
Q

Common or very common SE of MTX with oral use and parenteral use

A

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

High risk drugs afsha (5 decks)

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