Chapter 8: Immune system and malignant disease Flashcards
What are some main side effects of azathioprine?
- Hypersensitivity reactions - fever, rash
- Neutropenia and thrombocytopenia
- Nausea
What pre-treatment screening is needed with azathioprine?
TPMT levels
TPMT metabolises the drug, so if reduced levels, there is an increased risk of myelosuppression
What is the MHRA advice regarding ciclosporin prescribing?
Must be prescribed and dispensed by brand name
What is the MHRA advice surrounding tacrolimus prescribing?
Prescribe and dispense by brand name only, to minimise the risk of inadvertent switching between products, which has been associated with reports of toxicity and graft rejection
When monitoring tacrolimus, should peak or trough levels be taken?
Trough
Especially when there is diarrhoea, levels need to be closely monitored
What is the MHRA advice surrounding the use of mycophenolic acid/MMF?
The MHRA advises to exclude pregnancy in females of child-bearing potential before treatment—2 pregnancy tests 8–10 days apart are recommended. Women should use at least 1 method of effective contraception before and during treatment, and for 6 weeks after discontinuation - 2 are preferred
Mycophenolate medicines remain contraindicated in women of childbearing potential who are not using reliable contraception and in pregnant women unless there are no suitable alternatives to prevent transplant rejection
Male patients or their female partner should use effective contraception during treatment and for 90 days after discontinuation.
Fingolimod, a drug used for MS, carry what MHRA warnings?
- Signal of rebound effect after stopping or switching therapy
- Not recommended for patients at known risk of cardiovascular events e.g. persistent bradycardia
- Has an immunosuppressive effect and can increase the risk of skin cancers and lymphoma - refer patients with any skin lesions
What is the MHRA advice surrounding the use of bevacizumab?
Risk of osteonecrosis of the jaw
What is the MHRA advice surrounding the use of EGFR inhibitors e.g. cetuximab?
Keratitis and ulcerative keratitis
In rare cases, this has resulted in corneal perforation and blindness
What is the MHRA advice surrounding the use of nivolumab?
Risk of organ transplant rejection
Which two cytotoxic drugs do not cause bone marrow suppression?
Vincristine
Bleomycin
Ciclosporin can cause what kinds of toxicity?
Neurotoxicity
Nephrotoxicity
What is the patient advice surrounding ciclosporin?
- Avoid live vaccines
- Avoid excess UV light
- Avoid high potassium diet and grapefruit juice
- Warning signs about immunsuppression
Maintain brand
Tacrolimus can cause what kinds of organ damage?
Nephrotoxicity Cardiomyopathy Neurotoxicity - headaches, tremors Hepatotoxicity Eye disorders- burred vision
Can also disturb glucose metabolism
What is the patient advice surrounding tacrolimus?
- Avoid live vaccines
- Avoid excess UV light
- Avoid high potassium diet and grapefruit juice
- Warning signs about immunsuppression
Maintain brand
What is a local reaction that can happen when IV cytotoxics are given?
Extravasation - severe local tissue necrosis
What are the main side effects of cytotoxics?
- Alopecia
- Nausea and vomiting
- Oral mucositis - important to maintain good oral hygiene
- Tumour lysis syndrome (due to destruction of malignant cells)
- Hyperuricaemia - this is associated with acute renal failure. Give allopurinol/rasburicase
- Bone marrow suppression apart from vincristine and bleomycin
- Thromboembolism - cancer itself increases this risk too
What are the features of tumour lysis syndrome?
Hyperkalaemia, hyperuricaemia, hyperphosphataemia with
hypocalcaemia; renal damage and arrhythmias
How are acute/delayed nausea and vomiting symptoms managed in low risk chemotherapy patients?
Dexamethasone or lorazepam
How are acute/delayed nausea and vomiting symptoms managed in high risk chemotherapy patients?
5HT3 antagonist e.g. ondansetron + dexamethasone + aprepritant
How are anticipatory nausea and vomiting symptoms managed in chemotherapy patients on a moderately emetic regimen?
Dexamethasone and 5HT3 antagonist
How are anticipatory nausea and vomiting symptoms managed in chemotherapy patients on a highly emetic regimen?
Dexamethasone and aprepitant
Which cytotoxic drug class has a high risk of cardiotoxicity and how is this prevented?
Anthracyclines - doxorubicine, epirubicine
An iron chelate derazoxane is given
What is given to counteract the folate-antagonist action of methotrexate in chemotherapy?
Folinic acid (calcium folinate)
This is also used in methotrexate overdose but does not work for antibiotics with anti-folate action e.g. trimethoprim
Mesna is given with what cytotoxic drugs and why?
Cyclophosphamide and ifosdamide
Prevents haemorhaegic cystitis as metabolites of the drugs cause a toxin (acrolein)
Cyclophosphamide and ifsfomide carry a risk of what?
What is done to prevent this?
Haemorrhaegic cystitis
MESNA is given to prevent urinary tract toxicity and increasing fluid intake for 24-48 hours after administration
What colour does doxorubicin turn your urine?
Red
Do normal or liposomal formulations of doxorubicin carry a higher risk of cardiotoxicity?
Normal formulations carry a higher risk
What monitoring needs to be done before starting doxorubicin?
ECG due to the cardiotoxicity
Monitor during treatment too
What are the main side effects of bleomycin?
- Hypersensitivity reactions
- Progressive pulmonary fibrosis - monitor for suspicious X-ray changes
- Respiratory failure
Should vinca alkaloids e.g. vincristine, vinblastine, be given IV or intrathecally?
Only ever IV
Intrathecal administration is
associated with severe neurotoxicity
What is the patient advice surrounding methotrexate?
- Weekly dose not daily
- The patient must report any signs of blood disorders i.e. sore throat, bruising, mouth ulcers), liver toxicity (i.e. nausea, vomiting, abdominal pain and dark urine) and respiratory effects (SOB).
What are the serious side effects of methotrexate?
- Immunosuppression and blood disorders
- GI toxicity
- Stomatitis - inflammation of mouth and lips
- Liver toxicity
- Pulmonary toxicity
How is it recommended that methotrexate tablets are dispensed?
Single strength tablets only to avoid confusion, usually 2.5mg tablets
What is the MHRA warning regarding the use of imatinib?
Can cause reactivation of Hepatitis B
What is the first sign of methotrexate GI toxicity?
Stomatitis
Inflammation of mouth and lips
What are the pre-treatment screening requirements for methotrexate?
Exclude pregnancy before treatment
FBC, renal function and LFTs
What needs to be monitored in a patient on methotrexate and how often?
Have full blood count and renal and liver function tests repeated every 1–2 weeks until therapy stabilised, thereafter patients should be monitored every 2–3 months
What OTC medicines should a patient on methotrexate not have?
NSAIDs - aspirin, ibuprofen
Patients should be counselled on the use of NSAIDs
True or false:
Penicillins increase toxicity risk of methotrexate
True
How does allopurinol and azathioprine/mercaptopurine interact?
Azathioprine/mercaptopurine inhibits purine metabolism
Allopurinol also does this
Reduced dose is needed if given with allopurinol to reduce risk of toxicity
What are the main side effects of MMF to look out for?
Bone marrow suppression
Hypogammaglobinaemia - measure serum immunoglobulin if experiencing recurrent infections
Bronchiectasis - Look out for cough, SOB
What does the MHRA suggest for excluding pregnancy when starting MMF?
The MHRA advises to exclude pregnancy in females of child-bearing potential before treatment—2 pregnancy tests 8–10 days apart are recommended.
Pregnancy prevention programme
What kind of juice should be avoided if on tacrolimus?
Grapefruit juice
What is neoadjuvant chemotherapy?
Delivered before the main treatment e.g. to shrink the tumour
What role does febuxostat play in chemotherapy patients?
Prophylaxis and treatment of acute hyperuricaemia
Started 2 days before chemo
Rasburicase is used for the treatment of acute hyperuricaemia in what kind of cancer?
Blood cancers
What is a common side effect of doxurubicin (more common with liposomal formulations)?
Hand-foot syndrome
May be prevented by cooling hands and feet and avoiding socks, gloves, or tight-fitting footwear
What biomarker can you measure to see if you need to reduce the dose of doxorubicin?
Doxorubicin is largely excreted in the bile and an elevated bilirubin concentration is an indication for reducing the dose.
What bags should vincristine and vinblastine go in for adults and teenagers to prevent it from being administered intrathecally?
50mL mini bag
Should also have a sticker on to say “For IV use only”
What is the contraception advice for men and women on methotrexate?
Use effective contraception for at least 6 months after treatment
