- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Infusions of ciclosporin.
Prevention of rejection following bone marrow and stem cell transplantation
Prevention of rejection following solid organ transplant
Prophylaxis of graft-versus-host disease (GVHD)
Treatment of graft-versus-host disease (GVHD)
Treatment of transplant rejection after use of other immunosuppressants
Prevention of transplant rejection following solid organ transplants.
Treatment of organ transplant rejection in patients who previously received other immunosuppressive agents.
Prevention of transplant rejection following allogeneic bone marrow and stem cell transplantation.
Prophylaxis of graft-versus-host disease (GVHD) following allogeneic bone marrow transplant.
Treatment of established graft-versus-host disease (GVHD) following allogeneic bone marrow transplant.
Whilst the doses stated below are those recommended by the manufacturer, local protocols for the relevant indication should be consulted.
Solid organ transplantation
Oral treatment is preferred, but where necessary ciclosporin may be administered as a intravenous infusion at one third of the recommended oral dose.
Patients should be transferred to oral ciclosporin formulations as soon as their clinical condition allows.
Oral dose: Initially, a single oral dose of 10mg to 15mg/kg body weight, should be given 4 to 12 hours before transplantation. As a general rule, treatment should continue at a dose of 10mg to 15mg/kg/day for 1 to 2 weeks post-operatively. Dosage should then be gradually reduced until a maintenance dose of 2mg to 6mg/kg/day is reached. Dosage should be adjusted by monitoring ciclosporin blood levels and kidney function. When ciclosporin is given with other immunosuppressants (e.g. with corticosteroids or as part of a triple or quadruple drug therapy) lower doses (e.g. 3mg to 6mg/kg/day orally initially) may be used.
Bone-marrow transplantation, prevention and treatment of graft-versus- host disease:
Intravenous administration is usually preferred for initiation of therapy and should be given at a dose of 3mg to 5mg/kg daily over 2 to 6 hours from day before transplantation up to 2 weeks post-operatively until oral maintenance therapy is possible. Treatment should be continued for 6 months (but at least 3 months) before dose is gradually decreased to zero by 1 year after transplantation.
If graft-versus-host disease develops after ciclosporin therapy is discontinued. It should respond to reinstitution of therapy. Low doses should be used for mild, chronic graft-versus-host disease.
Severe Acute Ulcerative Colitis (unlicensed):
2mg/kg daily over 24 hours by continuous intravenous infusion. Dose titrated to response and blood levels.
(See Dosage; Adult)
Experience of ciclosporin for all indications in the elderly is limited, but no particular problems have been reported with dosing at the recommended adult dose. However, factors sometimes associated with ageing, particularly impaired renal function, make careful supervision essential and may necessitate dosage adjustment.
Organ and bone marrow transplantation
Clinical studies have included children from the age of 1 year. In several studies paediatric patients tolerated higher doses per kg body weight that adults.
Refractory ulcerative colitis (unlicensed):
Children aged 3 to 18 years: Initially 0.5mg/kg to 1mg/kg twice daily, dose titrated to response and blood levels.
The concentrate for infusion is for intravenous administration over a period of 2 to 6 hours after dilution.
Neonates under 1 month
Precautions and Warnings
Children under 3 months
Administration of live vaccines is not recommended
Correct serum magnesium levels before commencing treatment
Premedication with antihistamine recommended
Treatment to be initiated and supervised by a specialist
Infusion concentrate contains polyoxyethylene hydrogenated castor oil
Resuscitation facilities must be immediately available
Monitor blood lipids before and during treatment
Consider immunosuppressant adjustment in the event of PML
Elderly: Monitor renal function and consider dose modification
Monitor and control serum magnesium levels in the peri-transplant period
Monitor blood pressure
Monitor for hypersensitivity reactions during infusion
Monitor hepatic function
Monitor renal function
Monitor serum potassium regularly
Advise patient to report headaches, seizures, confusion, visual disturbance
Consider immunosuppressant adjustment if BK virus nephropathy develops
Consider immunosuppressant adjustment if polyomavirus nephropathy develops
Immunosuppressive drugs may increase risk of malignancy
May reduce effectiveness of vaccinations during treatment
Monitor for hypersensitivity reactions for at least 30 mins after admin
Oversuppression of immune system may increase susceptibility to infection
Discontinue if anaphylactoid reaction occurs
Discontinue if benign intracranial hypertension develops
Advise patient not to take echinacea products concurrently
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Avoid high dietary potassium intake
Advise patient to avoid exposure to sunlight and UV rays during treatment
During long-term therapy, some patients may develop structural changes in the kidney which in renal transplant recipients must be distinguished from chronic rejection.
In renal transplant patients, acute tubular necrosis is more likely if the machine perfusion time is more than 24 hours and the reanastomosis time more than 45 minutes.
In elderly patients, renal function should be regularly monitored. Hyperuricaemia may be aggravated by ciclosporin treatment.
Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.
Ciclosporin can cause gingival hyperplasia therefore routine dental check-ups (e.g. every three months) are recommended. In order to preclude or reduce gingival hyperplasia, teeth should be cleaned professionally and the patient should be instructed about measures necessary for personal dental hygiene.
Ciclosporin should be withdrawn immediately if benign intracranial hypertension is suspected due to risk of permanent visual loss.
Pregnancy and Lactation
Use ciclosporin with caution in pregnancy.
Ciclosporin should only be used when the benefits outweigh the risks.
Data available from organ transplant recipients indicate that, compared with other immunosuppressive agents, ciclosporin treatment imposes no increased risk of adverse effects on the course or outcome of pregnancy, however there is an increased risk of premature birth.
Exposure to ciclosporin does not justify termination of pregnancy. A detailed foetal ultrasound examination should be offered to confirm normal morphologic development in the case of first-trimester exposure.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Ciclosporin is contraindicated in breastfeeding.
Ciclosporin is excreted into breast milk, although the concentrations are relatively low. A risk to neonates cannot be excluded.
Schaefer considers that this drug should pose no obstacle to breastfeeding, as long as breastfeeding did not take place for at least four hours after ciclosporin administration so as to avoid peak ciclosporin levels in milk.
LactMed states that limited information indicates that ciclosporin produces low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than two months.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Acute respiratory distress
Acute tubular necrosis
Benign intracranial hypertension
BK virus associated with nephropathy
Blood pressure changes
Decrease in mental acuity
Haemolytic uraemic syndrome
Increased susceptibility to infection
Microangiopathic haemolytic anaemia syndrome
Optic disc oedema
Pain in lower extremities
Polyomavirus associated nephropathy
Posterior reversible encephalopathy syndrome (PRES)
Progressive multifocal leukoencephalopathy (PML)
Reactivation of infection
Renal structural changes
Serum creatinine increased
Thrombotic thrombocytopenic purpura
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: June 2016
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: Sandimmun concentrate for infusion 50mg/ml. Novartis Pharmaceuticals UK Ltd. Revised July 2015.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 August 2017
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Cyclosporine Last revised: 26 April 2016
Last accessed: 20 May 2016
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.