High risk drugs Part 1

Question 1

Methotrexate adverse effects that patients should report which may indicate toxicity.

Answer 1

INFECTION / BLOOD DYSCRASIAS: sore throat, bruising or mouth ulcers
LIVER IMPAIRMENT: nausea, vomiting or dark urine
PULMONARY: dyspnoea or cough
BONE MARROW SUPPRESSION: ^drop WBC/platelet=> withdrawal, thrombocytopenia, liver cirrhosis

Question 2

MTX MOA?

Indicated for?

Answer 2

inhibit dihydrofolate reductase (DHFR), the enzyme responsible for the reduction of folic acid to its active form, which is an essential cofactor for purine and thymidylic acid synthesis, and hence DNA production

Chemotherapy; BC, neoplastic diseases
Autoimmune conditions: Crohns (unlicensed), RA, Psoriasis

Question 3

MTX dosing info

Pt counselling

Answer 3

Usually once weekly
Comes as 2.5mg and 10mg tabs
Can be taken with or without food
Drink enough fluid, dehydration increases toxicity risk
Do not take extra doses for symptom relief. Relief of symptoms is gradual, begins in 3-6 weeks after starting. Continued improvement occurs during the first 12 weeks of taking the medicine.

Question 4

MTX pulmonary toxicity

Answer 4

Pulmonary toxicity may be a special problem in rheumatoid arthritis. Manufacturer advises patients to seek medical attention if dyspnoea, cough or fever develops; monitor for symptoms at each visit—discontinue if pneumonitis suspected.

Question 5

Liver toxicity MTX

Answer 5

Tx should not be started or discontinued if any abnormality of LFT / biopsy is present.
Abnormalities can return to normal in 2 weeks after which tx may be recommenced. Persistent increases in liver transaminases may warrant dose reduction / discontinuation.

Question 6

Gastro-intestinal toxicity MTX

Answer 6

Manufacturuer advises withdraw treatment if stomatitis or diarrhoea develops—may be first sign of gastro-intestinal toxicity.

Question 7

Blood count MTX

Answer 7

Bone marrow suppression can occur abruptly; factors likely to increase toxicity: advanced age, renal impairment, and concomitant use with another anti-folate drug (e.g. trimethoprim). Manufacturer advises a clinically significant drop in white cell count or platelet count calls for immediate withdrawal of methotrexate and introduction of supportive therapy.

Question 8

Give folic acid to reduce side-effects.MTX

Answer 8

Folic acid decreases mucosal and gastrointestinal SE of MTX and may prevent hepatotoxicity; no evidence of a reduction in haematological SE. Folinic acid (as calcium folinate) may be required in acute toxicity.

Question 9

Contraception MTX
Pregnancy
BF

Answer 9

Manufacturer advises effective contraception during and for at least 6 months after treatment in men and women.
Avoid (teratogenic; fertility may be reduced during therapy but this may be reversible).
Discontinue breast-feeding—present in milk.

Question 10

MTX monitoring

• before treatment
• during treatment

Answer 10

Before tx: FBC RFT LFT

low-dose methotrexate patients should:

• have FBC, RFT, LFT repeated every 1–2 weeks until therapy stabilised, thereafter pts should be monitored every 2–3 months.
• report all symptoms + signs suggestive of infection, especially sore throat

Treatment with folinic acid (as calcium folinate) may be required in acute toxicity.

Question 11

Folinic acid helps

MTX

Answer 11

Folinic acid following MTX administration helps to prevent MTX-induced mucositis and myelosuppression.

Question 12

T or F for MTX

Patients should be advised to avoid self-medication with over-the-counter aspirin or ibuprofen.

Answer 12

True

Question 13

T or F for MTX

NSAIDs can be used safely with MTX except for ibuprofen only

Answer 13

False

Patients should be counselled on the dose, treatment booklet, and the use of NSAIDs. There is some effect it can have as prostaglandin inhibition in kidneys may reduce renal perfusion affecting MTX clearance.

Question 14

Patient information for MTX

Answer 14

Patients and their carers should be warned to report immediately the onset of any feature of blood disorders (e.g. sore throat, bruising, and mouth ulcers), liver toxicity (e.g. nausea, vomiting, abdominal discomfort and dark urine), and respiratory effects (e.g. shortness of breath).
Methotrexate treatment booklets
A patient alert card should be provided to patients on once-weekly dosing
Avoid alcohol
Sunscreen for sun sensitivity
Folic acid on different day to MTX
Try to avoid taking with milk rich foods / caffeine
Avoid touching tab with hands

Question 15

MTX interactions

Answer 15

PPI, ^MTX, reduce prostaglandin reduced renal perfusion and MTX clearance
Trimethoprim, ^MTX nephrotoxicity, both folate antagonists
Vaccines ^risk of infection
Echinaecea, caffeine
NSAIDs
Penicillins ^MTX, as weak acids can compete @kidney

Question 16

Signs of renal tox

Answer 16

Lethargy / Weakness (anaemia)
SOB
Generalized swelling (edema)
Loss of appetite
Congestive heart failure
Metabolic acidosis
High blood potassium(hyperkalemia)
Fatal heart rhythm disturbances (arrhythmias) including ventricular tachycardia and ventricularfibrillation

Question 17

Signs liver toxicity

Answer 17

Skin and eyes that appear yellowish (jaundice)
Abdominal pain and swelling.
Swelling in the legs and ankles.
Itchy skin.
Dark urine color.
Pale stool color.
Chronic fatigue.
Nausea or vomiting.

Question 18

Blood dyscrasias

Answer 18

medical conditions (hematologic disorders) that may affect the cellular or plasma components of theblood, the bone marrow, or the lymph tissue

Signs: sore throat, bruising, mouth ulcers

Question 19

Mr Smith is 75 yo suffers from RA.
Taking MTX for the past 3 months.
GP prescribed him an antibiotic for infection.
Mr Smith brings the prescription to your pharmacy, he tells you he was told by his grandson that certain antibiotics may interact with methotrexate. Which antibiotic below must be avoided when on MTX?

A. Amoxicillin
B. Trimethoprim
C. Flucloxacillin
D. Erythromycin
E. Nitrofurantoin

Answer 19

Trimethoprim

Question 20

MTX side effects

Answer 20

SE: skin reactions, diarrhoea, GI SE, anaemia, fatigue, increased risk of infection, ulcers