Immune System and Malignant Disease

Immunosuppressants – Drug Classes) What are the main classes of immunosuppressant drugs?

• Corticosteroids

• Biologics

• Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

Which drugs are included in biologics?

• Monoclonal antibodies

• TNF inhibitors

• Interleukin inhibitors

Which drugs are included in DMARDs?

• Anti-metabolites: Azathioprine, Mycophenolate mofetil

• Calcineurin inhibitors: Ciclosporin, Tacrolimus

• Heavy metal antagonists: Penicillamine

What infection precautions should all immunosuppressed patients follow?

• Higher infection risk, especially during the first 6 months

• Avoid contact with people with chickenpox or shingles

• Seek urgent medical advice after exposure

• Drug toxicity during incurrent illness in renal impairment and sepsis

Which vaccines are recommended for those immunosuppressed?

• Influenza

• Pneumococcal

• COVID-19

• Avoid live vaccines (risk of generalised infection)

When can immunosuppressant toxicity worsen?

• During intercurrent illness

• In renal impairment

• During sepsis

How does azathioprine work?

• Broken down into mercaptopurine

• Mercaptopurine inhibits DNA replication

Why must TPMT be checked before starting azathioprine?

• Azathioprine is metabolised by thiopurine methyltransferase (TPMT)

• Absent TPMT = contraindication (high toxicity risk)

• Reduced TPMT = requires closer monitoring

MHRA What pregnancy-related warning applies to azathioprine?

Risk of intrahepatic cholestasis of pregnancy

What important adverse effects should patients report with Azathioprine?

• Leucopenia/thrombocytopenia

  • Sore throat

  • Bruising

  • Bleeding

• Nausea (often improves; take after food)

• Hypersensitivity:

  • Fever

  • Rash

  • Malaise

  • Diarrhoea

  • Myalgia

  • Hypotension

What contraception advice is required with Azathioprine?

• Teratogenic

• Use contraception during treatment

• Continue contraception for 3 months after stopping

What monitoring is required with Azathioprine?

• FBC

• Renal function

• LFTs

When is monitoring required for Azathioprine?

• Every 2 weeks until stable for 6 weeks

• Then monthly for 3 months

• Then every 3 months

Which important drug interactions occur with azathioprine?

• Allopurinol → ↑ bone marrow suppression

  • Reduce azathioprine dose to 25%

• Trimethoprim → ↑ haematological toxicity

• ACE inhibitors → ↑ haematological toxicity

How does mycophenolate mofetil work?

• Inhibits proliferation of T and B lymphocytes

• Suppresses immune responses

Mycophenolate – MHRA Pregnancy Advice) What contraception advice is required?

Females:

• At least 1 reliable method (preferably 2)

• During treatment and 6 weeks after

Males (or female partner):

• Contraception during treatment and 90 days after

What cancer risks are associated with mycophenolate?

• Increased risk of lymphoma

• Increased risk of skin cancer

• Avoid UV light/sun exposure

What major adverse effects should be monitored in Mycophenolate?

• Neutropenia

• Hypogammaglobulinaemia

• Bronchiectasis/interstitial lung disease → report cough

• Pure red cell aplasia

• GI ulceration, bleeding, perforation → caution in GI issues

Which key drug interactions occur with Mycophenolate?

• Antacids/PPIs → reduce mycophenolate levels

• Telmisartan → increases mycophenolate concentration

• Aciclovir → increases aciclovir concentration

Monitoring requirements Mycophenolate

FBC, renal function, LFTs every 2 weeks till dose is stable for 6 weeks

Monthly for 3 months

then every 3 months

How does ciclosporin work?

• Calcineurin inhibitor

• Suppresses immune response

How should ciclosporin be prescribed?

Prescribe by brand name only

What important adverse effects can ciclosporin cause?

• Hyperlipidaemia

• Hyperuricaemia

• Hyperkalaemia

• Hyperglycaemia

• Hypertension

• Hypomagnesaemia

• Tremor/headache/convulsions

• Gingival hyperplasia

• Hirsutism/acne

• Renal impairment

• Liver impairment

What important safety advice should patients know with Ciclosporin/tacrolimus?

• Stop if uncontrolled hypertension develops

• Increased risk of lymphoma → report sore throat

• Increased risk of skin cancer

• Avoid sunlight/UV exposure

• Can impair vision/driving ability

• Avoid in pregnancy and breastfeeding

Which major interactions occur with ciclosporin/tacrolimus?

• CYP450 inhibitors/inducers

• Grapefruit juice → increases levels

• Reduces clearance of:

  • Digoxin

  • Colchicine

  • Statins

Ciclosporin eye drops and contacts

contact lenses should be removed for dose and worn 15 minutes after

Monitoring for Ciclosporin/tacrolimus

FBC, renal function, LFTs, blood glucose, blood pressure

Every 2 weeks → stable for 6 weeks

Every month 3 months

At least every 3 months

How does tacrolimus differ from ciclosporin?

Similar side effects but no gingival hyperplasia

What additional risks are associated with tacrolimus?

• QT prolongation

• Cardiomyopathy (children)

• Eye disorders → possible vision loss

• GI perforation (life-threatening)

What drug allergy contraindicates tacrolimus?

• Macrolide hypersensitivity

How does penicillamine work?

• Binds heavy metals and removes them

• Inhibits macrophage activity

What notable adverse effects can occur with Penicillamine?

• Higher toxicity in elderly → regardless of renal function

• Loss of taste

• Breast enlargement (men and women)

What monitoring is required with Penicillamine?

• FBC

• Renal function

• LFTs

• Urinalysis (blood/protein)

When is monitoring required with Penicillamine?

• Every 2 weeks until stable for 6 weeks

• Then monthly for 12 months

• Then every 3 months

Which key interactions occur with Penicillamine?

• Iron/antacids reduce absorption

  • Take penicillamine 2 hours later

• Nephrotoxic drugs → increased kidney toxicity

(DMARDs – When to Refer) Which symptoms require urgent review?

• Rash/pruritus

• Mouth ulcers/sore throat

• Fever

• Bruising/bleeding

• Nausea/vomiting/diarrhoea

• Weight loss

• Diffuse hair loss

• Breathlessness

• Infection/cough

• Peripheral neuropathy

What TB symptoms should be reported urgently with biologics?

• Persistent cough

• Coughing blood

• Weight loss

What other symptoms need urgent referral with biologics?

• Symptoms of heart failure

• Shortness of breath/dry cough (possible ILD)

• Lupus-like rash or erythema nodosum

• New abdominal pain or GI symptoms