High risk drugs Flashcards
• antibiotics • anticoagulants • antiHTN • chemotherapy • insulins • antidiabetic drugs • drugs with a narrow therapeutic index • non-steroidal anti-inflammatory drugs • methotrexate • opiates • parenteral drugs
Methotrexate adverse effects that patients should report which may indicate toxicity.
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
MTX MOA?
Indicated for?
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
MTX dosing info
Pt counselling
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.
MTX pulmonary toxicity
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.
Liver toxicity MTX
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.
Gastro-intestinal toxicity MTX
Manufacturuer advises withdraw treatment if stomatitis or diarrhoea develops—may be first sign of gastro-intestinal toxicity.
Blood count MTX
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.
Give folic acid to reduce side-effects.MTX
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.
Contraception MTX
Pregnancy
BF
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.
MTX monitoring
- before treatment
- during treatment
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.
Folinic acid helps
MTX
Folinic acid following MTX administration helps to prevent MTX-induced mucositis and myelosuppression.
T or F for MTX
Patients should be advised to avoid self-medication with over-the-counter aspirin or ibuprofen.
True
T or F for MTX
NSAIDs can be used safely with MTX except for ibuprofen only
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.
Patient information for MTX
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
MTX interactions
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
Signs of renal tox
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