Ciclosporin therapeutics (Drugs used in immune diseases)

Question 1

What drug class does ciclosporin belong to?

Answer 1

It is a calcineurin inhibitor

Question 2

What conditions can Ciclosporin be used for?

Answer 2

• IBD
• Immunosuppressive therapy in transplant patients
• Psoriasis
• Severe atopic dermatitis
• Rheumatoid arthritis

Question 3

What are the possible side effects of Ciclosporin?

Answer 3

• Gi side effects
• Headache
• Tremor
• Hypertension
• Renal impairment
• Hirsutism- abnormal hair growth

Question 4

Are the side effects of ciclosporin dose-dependent?

Answer 4

Yes- Usually if the dose is decreased, the side effects reduce or stop

Question 5

What are the risks associated with ciclosporin use?

Answer 5

Can cause immmunosuppresion= increased risk of infections
Increased risk of developing lymphomas and other malignancies e.g. skin
- This risk is increased with dose and duration of use
- Need to reduce exposure to UV light

Question 6

When is Ciclosporin use contraindicated?

Answer 6

• Abnormal baseline renal function- dose would be reduced if renal problems for 1 month, if this is ineffective then ciclosporin would be stopped
• Malignancy
• Uncontrolled hypertension
• Uncontrolled infection

Question 7

When is ciclosporin cautioned?

Answer 7

• Elderly
• Patients with gout
• Hepatic impairment- dose should be lowered as ciclosporin is exclusively hepatically metabolised by CYP 450 enzymes and is excreted

Question 8

How is ciclosporin metabolised and excreted?

Answer 8

Exclusively hepatically- metabolised by CYP 450 3A4 enzymes in the liver

Question 9

What monitoring should be carried out before initiating and during ciclosporin therapy?

Answer 9

• Renal function
• Hepatic function
• Blood pressure
• Lipid levels
• Electrolytes- potassium and magnesium
• uric acid

Blood ciclosporin concentrations

Question 10

What drugs can interact with ciclosporin?

Answer 10

As it is hepatically metabolised by CYP450 3A4 enzymes, many drugs can interact:
- CYP 450 inhibitors e.g. Macrolides, Diltiazem, Verapamil, Lercanidipine, Fluconazole, itraconazole, ketoconazole
- Grapefruit juice
As all of these increase blood ciclosporin levels and so increase adverse effects
- CYP450 inducers e.g. rifampicin, carbamazepine, phenobarbitol, phenytoin, st Johns wort = all decrease blood ciclosporin levels so therapeutic effect is not reached
- Statins = increases statin exposure
- Nephrotoxic drugs e.g. NSAIDs, methotrexate
- Drugs that can cause similar effects e.g. potassium-sparing diuretics

Question 11

What formulations are available for ciclosporin?

Answer 11

IV or oral
The dose for oral is approx 3x that of iv

Question 12

What is important when prescribing ciclosporin?

Answer 12

The brands of the oral solution formulation have different bioavailabilities, especially in transplant patients and so can’t be interchanged.
Need prescriber’s approval and monitoring before changing.
Should be prescribed via brand name.

Question 13

How should the oral ciclosporin solution be prepared for administration?

Answer 13

Should be diluted immediately before administration and not left to rest.
- Can be mixed with orange or apple juice to improve taste but NOT grapefruit juice

Question 14

How frequent is ciclosporin dosing?

Answer 14

BD- total daily dose should be split between two doses, never once daily!
dose should be taken at the same time each day with some proximity to food

Question 15

What effects does Ciclosporin have on immunosuppression activity?

Answer 15

• decreased clonal proliferation of cytotoxic t-cells from CD8+ precursor
• Decrease function of t-cells effector cells responsible for cell-mediated response