Short-term treatment of very severe atopic dermatitis
where conventional therapy ineffective or inappropriate
(administered on expert advice)
▶BY MOUTH
▶Child: 2. 5 mg/kg twice daily usual maximum duration
of 8 weeks but may be used for longer under specialist
supervision
Severe psoriasis where conventional therapy ineffective
or inappropriate (administered on expert advice)
▶BY MOUTH
▶Child:Initially 1. 25 mg/kg twice daily (max. per dose
2. 5 mg/kg twice daily), increased gradually to
maximum if no improvement within 1 month, initial
dose of 2. 5 mg/kg twice daily justified if condition
requires rapid improvement; discontinue if inadequate
response after 3 months at the optimum dose; max.
duration of treatment usually 1 year unless other
treatments cannot be used
Prevention of graft rejection following bone-marrow,
kidney, liver, pancreas, heart, lung, and heart-lung
transplantation|Prevention and treatment of graft-
versus-host disease
▶BY MOUTH, OR BY INTRAVENOUS INFUSION
▶Child:(consult local protocol)
Nephrotic syndrome
▶BY MOUTH
▶Child: 3 mg/kg twice daily, dose can be increased if
necessary in corticosteroid-resistant disease; for
maintenance reduce to lowest effective dose according
to whole blood-ciclosporin concentrations,
proteinuria, and renal function
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶With oral useManufacturer advises increase dose by 50 %
or switch to intravenous administration with concurrent
use of octreotide.lUNLICENSED USENot licensed for use in children under
3 months. Not licensed for use in children under 16 years
for atopic eczema (dermatitis) or psoriasis. Not licensed for
use in ulcerative colitis.IMPORTANT SAFETY INFORMATION
MHRA/CHM ADVICE: CICLOSPORIN MUST BE PRESCRIBED AND
DISPENSED BY BRAND NAME (DECEMBER 2009)
Patients should be stabilised on a particular brand of oral
ciclosporin because switching between formulations
without close monitoring may lead to clinically
important changes in blood-ciclosporin concentration.lCONTRA-INDICATIONSAbnormal baseline renal function
(in non-transplant indications).malignancy (in non-
transplant indications).uncontrolled hypertension (in
non-transplant indications).uncontrolled infections (in
non-transplant indications)
lCAUTIONSHyperuricaemia.in atopic dermatitis, active
herpes simplex infections—allow infection to clear before
starting (if they occur during treatment withdraw if severe)
.in atopic dermatitis,Staphylococcus aureusskin
infections—not absolute contra-indication providing
controlled (but avoid erythromycin unless no other
alternative).in psoriasis treat, patients with malignant or
pre-malignant conditions of skin only after appropriate
treatment (and if no other option).in uveitis, Behcet’s
syndrome (monitor neurological status).
lymphoproliferative disorders (discontinue treatment).
malignancy
CAUTIONS, FURTHER INFORMATION
▶MalignancyIn psoriasis, exclude malignancies (including
those of skin and cervix) before starting (biopsy any
lesions not typical of psoriasis) and treat patients with
malignant or pre-malignant conditions of skin only afterappropriate treatment (and if no other option);
discontinue if lymphoproliferative disorder develops.
lINTERACTIONS→Appendix 1 : ciclosporin
lSIDE-EFFECTS
▶Common or very commonAppetite decreased.diarrhoea.
electrolyte imbalance.fatigue.fever.flushing.
gastrointestinal discomfort.gingival hyperplasia.hair
changes.headaches.hepatic disorders.hyperglycaemia.
hyperlipidaemia.hypertension.hyperuricaemia.
leucopenia.muscle complaints.nausea.paraesthesia.
peptic ulcer.renal impairment (renal structural changes
on long-term administration).seizure.skin reactions.
tremor.vomiting
▶UncommonAnaemia.encephalopathy.oedema.
thrombocytopenia.weight increased
▶Rare or very rareEye inflammation.gynaecomastia.
haemolytic anaemia.idiopathic intracranial hypertension
.menstrual disorder.multifocal motor neuropathy.
muscle weakness.myopathy.pancreatitis
▶Frequency not knownPain in extremity.thrombotic
microangiopathy
lPREGNANCYCrosses placenta; manufacturer advises avoid
unless potential benefit outweighs risk—toxicity inanimal
studies.
lBREAST FEEDINGManufacturer advises avoid—present in
milk.
lHEPATIC IMPAIRMENTDose adjustmentsExtensively
metabolised by the liver—manufacturer advises consider
dose adjustment based on bilirubin and liver enzyme
levels.
lRENAL IMPAIRMENTDose adjustmentsIn non-transplant
indications, manufacturer advises establishing baseline
renal function before initiation of treatment; if baseline
function is impaired in non-transplant indications, except
nephrotic syndrome—avoid. In nephrotic syndrome,
manufacturer advises initial dose should not exceed
2. 5 mg/kg daily in patients with baseline renal impairment.
During treatmentfor non-transplant indications,
manufacturer recommends if the estimated glomerular
filtration rate decreases by more than 25 % below baseline
on more than one measurement, reduce dose by 25 – 50 %.
If the estimated glomerularfiltration rate decrease from
baseline exceeds 35 %, further dose reduction should be
considered (even if within normal range); discontinue if
reduction not successful within 1 month.
lMONITORING REQUIREMENTS
▶Monitor whole blood ciclosporin concentration (trough
level dependent on indication—consult local treatment
protocol for details).
▶In long-term management of nephrotic syndrome,
perform renal biopsies every 1 – 2 years.
lDIRECTIONS FOR ADMINISTRATION
▶With oral useMix solution with orange or apple juice, or
other soft drink (to improve taste) immediately before
taking (and rinse with more to ensure total dose). Do not
mix with grapefruit juice. Total daily dose should be taken
in 2 divided doses.
▶With intravenous useFor intermittentintravenous infusion,
dilute to a concentration of 0. 5 – 2. 5 mg/mL with Glucose
5 %orSodium Chloride 0. 9 %; give over 2 – 6 hours; not to
be used with PVC equipment. Observe patient for signs of
anaphylaxis for at least 30 minutes after starting infusion
and at frequent intervals thereafter.
lPRESCRIBING AND DISPENSING INFORMATION
Brand name prescribingPrescribing and dispensing of
ciclosporin should be by brand name to avoid inadvertent
switching. If it is necessary to switch a patient to a
different brand of ciclosporin, the patient should be
monitored closely for changes in blood-ciclosporin
concentration, serum creatinine, blood pressure, and
transplant function (for transplant indications).520 Immune system disorders and transplantation BNFC 2018 – 2019
Immune system and malignant disease8