Ciclosporin Therapeutics Flashcards
What is ciclosporin?
Ciclosporin is a calcineurin inhibitor.
What are the indications for ciclosporin?
- Inflammatory bowel disease
- Immunosuppressive therapy in transplant patients
- Psoriasis
- Severe atopic dertmatitis
- Rheumatoid arthritis
What is the available dosing for ciclosporin?
- Can be given orally (tablets/capsules/liquids) or intravenously
- Doses vary greatly for different conditions
- Dose often involves up titration - balance between effective treatment and tolerability/adverse effects
What are the side effects of using ciclosporin?
Very common:
- Headache
- Tremor
- Hypertension
- Hirtsutism (excess hair)
- Renal impairment
Common:
- GI
- Fatigue
- Convulsions (seizure)
- Muscle cramps
- Myalgia (muscle pain)
- Hyperglycaemia
- Hyperlipidaemia
- Hyperkalaemia
- Hyperuricasemia
- Hypomagnesaemia
- Hepatic impairment
Other important side effects:
- Immunosuppression increases the risk of infection
- Immunosuppression increases the risk of developing lymphomas and malignancies
Side effects are more common where higher doses and longer durations of use are involved.
In what patient groups is Ciclosporin contraindicated in?
- Elderly (they have natural reduced renal and hepatic impairment due to aging, increasing their susceptibility to adverse events)
- Gout (as a side effect is increase in uric acid - hyperuricaemia)
- Hepatic impairment -> dose reductions
What are the contraindications associated with Ciclosporin?
- Abnormal baseline renal function -> dose reductions -> no improvement within a month, Ciclosporin should be stopped
- Malignancy
- Uncontrolled hypertension
- Uncontrolled infection
What monitoring should be conducted at baseline therapy and throughout treatment with Ciclosporin?
- Renal function
- Hepatic function
- Blood pressure
- Lipids
- Electrolytes - potassium, magnesium
- Uric acid
What drugs interact with Ciclosporin?
Ciclosporin is metabolised by the CYP450 34A isoenzyme, therefore:
- CYP450 inhibitors
E.g. Macrolides, Diltiazem, Verapamil, Lercanidipine, Fluconazole, Itraconazole, Ketoconazole, Grapefruit juice
Use of ciclosporin with CYP450 inhibitors will increase blood levels of ciclosporin hence increasing the risk of adverse effects.
- CYP450 inducers
E.g. Rifampicin, Carbamazepine, Phenobarbital, Phenytoin, St. John Wort
Use of Ciclosporin with CYP450 inducers will reduce blood levels of ciclosporin hence you won’t get the predicted outcome and patients may not respond as well as their drug levels are much lower.
- Statins -> Avoid or dose reductions
- Nephrotoxic drugs - NSAIDs, Methotrexate
- Any drugs causing adverse effects seen with ciclosporin, i.e. K+ sparing diuretics (hyperkalaemia)
What is an important difference to consider in IV and oral preparations?
The oral dose of ciclosporin is approximately 3 times that of the IV formulation
- This is due to the differences of the bioavailability of the preparations partially due to the poor absorption of the oral preparation.
- Different oral preparations also have different bioavailabilites
The oral solution of ciclosporin should be diluted with what substance prior to administration?
It should be IMMEDIATELY diluted down with orange or apple juice before administration
- NO GRAPEFRUIT JUICE
What important counselling points should be provided to patients taking Ciclosporin?
- Importance of monitoring, i.e. making sure they have blood tests done
- This is a twice a day preparation
- They should be maintained on the same brand of ciclosporin
- Consistent in terms of administration - Around about the same time each day and within the same proximity to food
- Avoid live vaccines
