▶ Common or very common Eye inflammation
on long-term administration). seizure . skin reactions . tremor. vomiting
▶ Uncommon Anaemia . encephalopathy . oedema . thrombocytopenia . weight increased
▶ Frequency not known Pain in extremity .thrombotic
l PREGNANCY Crosses placenta; manufacturer advises avoid
unless potential benefit outweighs risk—toxicity in animal
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe impairment (risk of increased exposure).
Dose adjustments Manufacturer advises consider dose
Dose adjustments In 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 treatment
for non-transplant indications, manufacturer recommends
if eGFR decreases by more than 25% below baseline on
more than one measurement, reduce dose by 25–50%. If
the eGFR decrease from baseline exceeds 35%, further
dose reduction should be considered (even if within
normal range); discontinue if reduction not successful
▶ Monitor whole blood ciclosporin concentration (trough
level dependent on indication—consult local treatment
▶ Dermatological and physical examination, including blood
pressure and renal function measurements required at
least twice before starting treatment for psoriasis or atopic
▶ Monitor serum potassium, especially in renal dysfunction
▶ Measure blood lipids before treatment and after the first
▶ In psoriasis and atopic dermatitis monitor serum
creatinine every 2 weeks for first 3 months then every
▶ Investigate lymphadenopathy that persists despite
improvement in atopic dermatitis.
▶ Monitor kidney function—dose dependent increase in
serum creatinine and urea during first few weeks may
necessitate dose reduction in transplant patients (exclude
rejection if kidney transplant) or discontinuation in nontransplant patients.
▶ Monitor blood pressure—discontinue if hypertension
develops that cannot be controlled by antihypertensives.
▶ In long-term management of nephrotic syndrome,
perform renal biopsies at yearly intervals.
▶ In rheumatoid arthritis measure serum creatinine at least
twice before treatment. During treatment, monitor serum
creatinine every 2 weeks for first 3 months, then every
month for a further 3 months, then every 4–8 weeks
depending on the stability of the disease, concomitant
medication, and concomitant diseases (or more frequently
if dose increased or concomitant NSAIDs introduced or
▶ Monitor hepatic function if concomitant NSAIDs given.
l DIRECTIONS FOR ADMINISTRATION
▶ With oral use Mix 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
▶ With intravenous use For intravenous infusion (Sandimmun ®),
give intermittently or continously in Glucose 5% or Sodium
Chloride 0.9%; dilute to a concentration of 50 mg in
20–100 mL; give intermittent infusion 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.
l PRESCRIBING AND DISPENSING INFORMATION
Brand name prescribing Prescribing 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).
Sandimmun ® capsules and oral solution are available
direct from Novartis for patients who cannot be
transferred to a different oral preparation.
l PATIENT AND CARER ADVICE Patients and carers should be
counselled on the administration of different formulations
of ciclosporin. Manufacturer advises avoid excessive
exposure to UV light, including sunlight. In psoriasis and
atopic dermatitis, avoid use of UVB or PUVA.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 11
EXCIPIENTS: May contain Alcohol, polyoxyl castor oils
▶ Sandimmun (Novartis Pharmaceuticals UK Ltd)
Ciclosporin 50 mg per 1 ml Sandimmun 250mg/5ml concentrate for
solution for infusion ampoules | 10 ampoule P £110.05
Sandimmun 50mg/1ml concentrate for solution for infusion ampoules
CAUTIONARY AND ADVISORY LABELS 11
EXCIPIENTS: May contain Alcohol, propylene glycol
▶ Capsorin (Morningside Healthcare Ltd)
Ciclosporin 100 mg per 1 ml Capsorin 100mg/ml oral solution sugarfree | 50 ml P £86.96 DT = £164.72
▶ Neoral (Novartis Pharmaceuticals UK Ltd)
Ciclosporin 100 mg per 1 ml Neoral 100mg/ml oral solution sugarfree | 50 ml P £102.30 DT = £164.72
▶ Sandimmun (Novartis Pharmaceuticals UK Ltd)
Ciclosporin 100 mg per 1 ml Sandimmun 100mg/ml oral solution
sugar-free | 50 ml P £164.72 DT = £164.72
CAUTIONARY AND ADVISORY LABELS 11
EXCIPIENTS: May contain Ethanol, ethyl lactate, propylene glycol
▶ Ciclosporin (Non-proprietary)
Ciclosporin 25 mg Ciclosporin 25mg capsules | 30 capsule P s
Ciclosporin 50 mg Ciclosporin 50mg capsules | 30 capsule P s
BNF 78 Immune system disorders and transplantation 839
Immune system and malignant disease
Ciclosporin 100 mg Ciclosporin 100mg capsules | 30 capsule P s DT = £68.28
Ciclosporin 25 mg Capimune 25mg capsules | 30 capsule P £13.05 DT = £18.37
Ciclosporin 50 mg Capimune 50mg capsules | 30 capsule P £25.50 DT = £35.97
Ciclosporin 100 mg Capimune 100mg capsules | 30 capsule P £48.50 DT = £68.28
▶ Capsorin (Morningside Healthcare Ltd)
Ciclosporin 25 mg Capsorin 25mg capsules | 30 capsule P £11.14 DT = £18.37
Ciclosporin 50 mg Capsorin 50mg capsules | 30 capsule P £21.80 DT = £35.97
Ciclosporin 100 mg Capsorin 100mg capsules | 30 capsule P £41.59 DT = £68.28
▶ Deximune (Dexcel-Pharma Ltd)
Ciclosporin 25 mg Deximune 25mg capsules | 30 capsule P £13.06 DT = £18.37
Ciclosporin 50 mg Deximune 50mg capsules | 30 capsule P £25.60 DT = £35.97
Ciclosporin 100 mg Deximune 100mg capsules | 30 capsule P £48.90 DT = £68.28
▶ Neoral (Novartis Pharmaceuticals UK Ltd)
Ciclosporin 10 mg Neoral 10mg capsules | 60 capsule P £18.25
Ciclosporin 25 mg Neoral 25mg capsules | 30 capsule P £18.37
Ciclosporin 50 mg Neoral 50mg capsules | 30 capsule P £35.97
Ciclosporin 100 mg Neoral 100mg capsules | 30 capsule P £68.28 DT = £68.28
▶ Sandimmun (Novartis Pharmaceuticals UK Ltd)
Ciclosporin 25 mg Sandimmun 25mg capsules | 30 capsule P £29.58 DT = £18.37
Ciclosporin 50 mg Sandimmun 50mg capsules | 30 capsule P £57.92 DT = £35.97
Ciclosporin 100 mg Sandimmun 100mg capsules | 30 capsule P £109.93 DT = £68.28
Ciclosporin 10 mg Vanquoral 10mg capsules | 60 capsule P £12.75 DT = £18.25
Ciclosporin 25 mg Vanquoral 25mg capsules | 30 capsule P £13.05 DT = £18.37
Ciclosporin 50 mg Vanquoral 50mg capsules | 30 capsule P £25.59 DT = £35.97
Ciclosporin 100 mg Vanquoral 100mg capsules | 30 capsule P £48.89 DT = £68.28
l DRUG ACTION Sirolimus is a non-calcineurin inhibiting
Prophylaxis of organ rejection in kidney allograft
▶ Adult: Initially 6 mg for 1 dose, to be given after
surgery once wound has healed, then 2 mg once daily;
to be given in combination with ciclosporin and
corticosteroid for 2–3 months (sirolimus doses should
be given 4 hours after ciclosporin), ciclosporin should
then be withdrawn over 4–8 weeks (if not possible,
sirolimus should be discontinued and an alternate
immunosuppressive regimen used), dose to be adjusted
according to whole blood-sirolimus trough
DOSE EQUIVALENCE AND CONVERSION
▶ The 500 microgram tablet is not bioequivalent to the
1 mg and 2 mg tablets. Multiples of 500 microgram
tablets should not be used as a substitute for other
l CAUTIONS Hyperlipidaemia . increased susceptibility to
infection (especially urinary-tract infection). increased
susceptibility to lymphoma and other malignancies,
particularly of the skin (limit exposure to UV light)
l INTERACTIONS → Appendix 1: sirolimus
▶ Uncommon Antibiotic associated colitis . focal segmental
▶ Frequency not known Posterior reversible encephalopathy
l CONCEPTION AND CONTRACEPTION Effective
contraception must be used during treatment and for
l PREGNANCY Avoid unless essential—toxicity in animal
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution (risk
Dose adjustments Manufacturer advises maintenance dose
reduction of approx. 50% in severe impairment—monitor
whole blood-sirolimus trough concentration every
5–7 days until 3 consecutive measurements have shown
stable blood-sirolimus concentration.
▶ Monitor whole blood-sirolimus trough concentration
(Afro-Caribbean patients may require higher doses).
when used with ciclosporin should be
4–12 micrograms/litre (local treatment protocols may
differ); after withdrawal of ciclosporin pre-dose whole
blood-sirolimus concentration should be
12–20 micrograms/litre (local treatment protocols may
▶ Close monitoring of whole blood-sirolimus concentration
required if concomitant treatment with potent inducers or
inhibitors of metabolism and after discontinuing them, or
if ciclosporin dose reduced significantly or stopped.
▶ When changing between oral solution and tablets,
measurement of whole blood ‘trough’ sirolimus
concentration after 1–2 weeks is recommended.
▶ Therapeutic drug monitoring assays Sirolimus whole-blood
concentration is measured using either high performance
liquid chromatography (HPLC) or immunoassay. Switching
between different immunoassays or between an
immunoassay and HPLC can lead to clinically significant
differences in results and therefore incorrect dose
adjustments. Adjustment to the target therapeutic dose
range should be made with knowledge of the assay used
and corresponding reference range.
▶ Monitor kidney function when given with ciclosporin;
monitor lipids; monitor urine proteins.
l DIRECTIONS FOR ADMINISTRATION Food may affect
absorption (take at the same time with respect to food).
Sirolimus oral solution should be mixed with at least 60 mL
water or orange juice in a glass or plastic container
immediately before taking; refill container with at least
120 mL of water or orange juice and drink immediately (to
ensure total dose). Do not mix with any other liquids.
840 Immune system disorders and transplantation BNF 78
Immune system and malignant disease
l PATIENT AND CARER ADVICE Patient or carers should be
given advice on how to administer sirolimus.
Patients should be advised to avoid excessive exposure
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Immunosuppressive therapy for kidney transplant in adults
Sirolimus is not recommended as an initial treatment to
prevent organ rejection in adults having a kidney
transplant. Patients whose treatment was started within
the NHS before this guidance was published should have
the option to continue treatment, without change to their
funding arrangements, until they and their NHS clinician
consider it appropriate to stop.
www.nice.org.uk/guidance/TA481
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Ethanol
Sirolimus 1 mg per 1 ml Rapamune 1mg/ml oral solution sugar-free
| 60 ml P £162.41 DT = £162.41
Sirolimus 500 microgram Rapamune 0.5mg tablets |
30 tablet P £69.00 DT = £69.00
Sirolimus 1 mg Rapamune 1mg tablets | 30 tablet P £86.49 DT =
Sirolimus 2 mg Rapamune 2mg tablets | 30 tablet P £172.98 DT
l DRUG ACTION Tacrolimus is a calcineurin inhibitor.
Prophylaxis of graft rejection following liver
transplantation, starting 12 hours after transplantation
▶ Adult: Initially 100–200 micrograms/kg daily in
Prophylaxis of graft rejection following kidney
transplantation, starting within 24 hours of
▶ Adult: Initially 200–300 micrograms/kg daily in
Prophylaxis of graft rejection following heart
transplantation following antibody induction, starting
within 5 days of transplantation
▶ Adult: Initially 75 micrograms/kg daily in 2 divided
Prophylaxis of graft rejection following heart
transplantation without antibody induction, starting
within 12 hours of transplantation
▶ Adult: Initially 75 micrograms/kg daily in 2 divided
Allograft rejection resistant to conventional
▶ Adult: Seek specialist advice
Prophylaxis of graft rejection following liver
transplantation, starting 12–18 hours after
▶ Adult: Initially 100–200 micrograms/kg once daily, to
Prophylaxis of graft rejection following kidney
transplantation, starting within 24 hours of
▶ Adult: Initially 200–300 micrograms/kg once daily, to
Allograft rejection resistant to conventional
▶ Adult: Seek specialist advice
ENVARSUS ® MODIFIED-RELEASE TABLETS
Prophylaxis of graft rejection following liver
transplantation, starting within 24 hours of
▶ Adult: Initially 110–130 micrograms/kg once daily, to
Prophylaxis of graft rejection following renal
transplantation, starting within 24 hours of
▶ Adult: Initially 170 micrograms/kg once daily, to be
▶ Adult: Seek specialist advice
Prophylaxis of graft rejection following liver
transplantation, starting 12 hours after transplantation
▶ Adult: Initially 100–200 micrograms/kg daily in
Prophylaxis of graft rejection following kidney
transplantation, starting within 24 hours of
▶ Adult: Initially 200–300 micrograms/kg daily in
Prophylaxis of graft rejection following heart
transplantation following antibody induction, starting
within 5 days of transplantation
▶ Adult: Initially 75 micrograms/kg daily in 2 divided
Prophylaxis of graft rejection following heart
transplantation without antibody induction, starting
within 12 hours of transplantation
▶ Adult: Initially 75 micrograms/kg daily in 2 divided
▶ Adult: Seek specialist advice
Prophylaxis of graft rejection following liver
transplantation, starting 12 hours after transplantation
▶ Adult: Initially 100–200 micrograms/kg daily in
BNF 78 Immune system disorders and transplantation 841
Immune system and malignant disease
Prophylaxis of graft rejection following kidney
transplantation, starting within 24 hours of
▶ Adult: Initially 200–300 micrograms/kg daily in
Prophylaxis of graft rejection following heart
transplantation following antibody induction, starting
within 5 days of transplantation
▶ Adult: Initially 75 micrograms/kg daily in 2 divided
Prophylaxis of graft rejection following heart
transplantation without antibody induction, starting
within 12 hours of transplantation
▶ Adult: Initially 75 micrograms/kg daily in 2 divided
Allograft rejection resistant to conventional
▶ Adult: Seek specialist advice
Prophylaxis of graft rejection following liver
transplantation, starting 12 hours after transplantation
when oral route not appropriate
▶ Adult: Initially 10–50 micrograms/kg daily for up to
7 days (then transfer to oral therapy), dose to be
Prophylaxis of graft rejection following kidney
transplantation, starting within 24 hours of
transplantation when oral route not appropriate
▶ Adult: Initially 50–100 micrograms/kg daily for up to
7 days (then transfer to oral therapy), dose to be
Prophylaxis of graft rejection following heart
transplantation following antibody induction, starting
within 5 days of transplantation
▶ Adult: Initially 10–20 micrograms/kg daily for up to
7 days (then transfer to oral therapy), dose to be
Prophylaxis of graft rejection following heart
transplantation without antibody induction, starting
within 12 hours of transplantation
▶ Adult: Initially 10–20 micrograms/kg daily for up to
7 days (then transfer to oral therapy), dose to be
Allograft rejection resistant to conventional
▶ BY CONTINUOUS INTRAVENOUS INFUSION
▶ Adult: Seek specialist advice (consult local protocol)
MHRA/CHM ADVICE: ORAL TACROLIMUS PRODUCTS: PRESCRIBE
AND DISPENSE BY BRAND NAME ONLY, TO MINIMISE THE RISK OF
INADVERTENT SWITCHING BETWEEN PRODUCTS, WHICH HAS BEEN
ASSOCIATED WITH REPORTS OF TOXICITY AND GRAFT REJECTION
Inadvertent switching between oral tacrolimus products
has been associated with reports of toxicity and graft
rejection. To ensure maintenance of therapeutic
response when a patient is stabilised on a particular
brand, oral tacrolimus products should be prescribed and
morning and once in the evening;
once in the morning and once in the evening;
. Advagraf ® is a prolonged-release capsule that is taken
Switching between tacrolimus brands requires careful
supervision and therapeutic monitoring by an
Important: Envarsus ® is not interchangeable with
other oral tacrolimus containing products; the MHRA
has advised (June 2012) that oral tacrolimus products
should be prescribed and dispensed by brand only.
excessive exposure to sunlight and sunlamps)
l INTERACTIONS → Appendix 1: tacrolimus
conditions . bile duct disorders . confusion . consciousness
discomfort. gastrointestinal disorders . gastrointestinal
disorders . pain . peripheral neuropathy . peripheral
necrosis .respiratory disorders . seizure . sensation
abnormal . skin reactions . sleep disorders .temperature
obstruction syndrome .thirst. ulcer
▶ Frequency not known Agranulocytosis . neoplasm
malignant. neoplasms . polyomavirus-associated
nephropathy . progressive multifocal leukoencephalopathy
▶ With intravenous use Anaphylactoid reaction (due to
842 Immune system disorders and transplantation BNF 78
Immune system and malignant disease
SIDE-EFFECTS, FURTHER INFORMATION Cardiomyopathy
has been reported to occur primarily in children with
tacrolimus blood trough concentrations much higher than
the recommended maximum levels. Patients should be
monitored by echocardiography for hypertrophic
changes—consider dose reduction or discontinuation if
l ALLERGY AND CROSS-SENSITIVITY Contra-indicated if
history of hypersensitivity to macrolides.
l CONCEPTION AND CONTRACEPTION Exclude pregnancy
l PREGNANCY Avoid unless potential benefit outweighs
risk—crosses the placenta and risk of premature delivery,
intra-uterine growth restriction, and hyperkalaemia.
l BREAST FEEDING Avoid—present in breast milk (following
l HEPATIC IMPAIRMENT Manufacturer advises caution in
Dose adjustments Manufacturer advises consider dose
reduction in severe impairment.
▶ After initial dosing, and for maintenance treatment,
trough concentration (especially during episodes of
diarrhoea)—consult local treatment protocol for details.
▶ Monitor blood pressure, ECG (for hypertrophic changes—
risk of cardiomyopathy), fasting blood-glucose
concentration, haematological and neurological (including
visual) and coagulation parameters, electrolytes, hepatic
l DIRECTIONS FOR ADMINISTRATION
▶ With intravenous use For intravenous infusion (Prograf ®);
give continuously in Glucose 5% or Sodium Chloride 0.9%.
Dilute concentrate in infusion fluid to a final
concentration of 4–100 micrograms/mL; give over
24 hours. Tacrolimus is incompatible with PVC.
l PATIENT AND CARER ADVICE Avoid excessive exposure to
Driving and skilled tasks May affect performance of skilled
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Immunosuppressive therapy for kidney transplant in adults
Immediate-release tacrolimus, when used as part of an
immunosuppressive regimen, is recommended as an initial
option to prevent organ rejection in adults having a kidney
transplant. Treatment should be started with the least
expensive product, but if this is not suitable, an alternative
dosage form may be given. Tacrolimus granules for oral
suspension (Modigraf ®) should be used only if the
manufacturer provides it at the same price or lower than
that agreed with the Commercial Medicines Unit. Patients
whose treatment was started within the NHS before this
guidance was published should have the option to
continue treatment, without change to their funding
arrangements, until they and their NHS clinician consider
www.nice.org.uk/guidance/TA481
▶ Immunosuppressive therapy for kidney transplant in adults
Prolonged-release tacrolimus is not recommended as an
initial treatment to prevent organ rejection in adults
having a kidney transplant. Patients whose treatment was
started within the NHS before this guidance was published
should have the option to continue treatment, without
change to their funding arrangements, until they and their
NHS clinician consider it appropriate to stop.
www.nice.org.uk/guidance/TA481
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (December
2010) that tacrolimus granules for suspension (Modigraf ®)
are accepted for restricted use within NHS Scotland in
patients for whom tacrolimus is an appropriate choice of
immunosuppressive therapy and where small changes (less
than 500 micrograms) in dosing increments are required
(such as, in paediatric patients) or in seriously ill patients
who are unable to swallow tacrolimus capsules.
The Scottish Medicines Consortium has advised (April
2015) that tacrolimus (Envarsus ®) is accepted for use in
NHS Scotland for prophylaxis of graft rejection and
treatment of rejection resistant to treatment with other
immunosuppressive medicinal products in adults.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Tacrolimus (as Tacrolimus monohydrate)
750 microgram Envarsus 750microgram modified-release tablets | 30 tablet P £44.33 DT = £44.33
Tacrolimus (as Tacrolimus monohydrate) 1 mg Envarsus 1mg
modified-release tablets | 30 tablet P £59.10 DT = £59.10
Tacrolimus (as Tacrolimus monohydrate) 4 mg Envarsus 4mg
modified-release tablets | 30 tablet P £236.40 DT = £236.40
CAUTIONARY AND ADVISORY LABELS 13, 23
▶ Modigraf (Astellas Pharma Ltd)
Tacrolimus (as Tacrolimus monohydrate)
200 microgram Modigraf 0.2mg granules sachets sugar-free |
50 sachet P £71.30 DT = £71.30
Tacrolimus (as Tacrolimus monohydrate) 1 mg Modigraf 1mg
granules sachets sugar-free | 50 sachet P £356.65 DT = £356.65
CAUTIONARY AND ADVISORY LABELS 23, 25
▶ Advagraf (Astellas Pharma Ltd)
Tacrolimus (as Tacrolimus monohydrate)
500 microgram Advagraf 0.5mg modified-release capsules |
50 capsule P £35.79 DT = £35.79
Tacrolimus (as Tacrolimus monohydrate) 1 mg Advagraf 1mg
modified-release capsules | 50 capsule P £71.59 DT = £71.59 | 100 capsule P £143.17 DT = £143.17
Tacrolimus (as Tacrolimus monohydrate) 3 mg Advagraf 3mg
modified-release capsules | 50 capsule P £214.76 DT = £214.76
Tacrolimus (as Tacrolimus monohydrate) 5 mg Advagraf 5mg
modified-release capsules | 50 capsule P £266.92 DT = £266.92
EXCIPIENTS: May contain Polyoxyl castor oils
▶ Prograf (Astellas Pharma Ltd)
Tacrolimus 5 mg per 1 ml Prograf 5mg/1ml solution for infusion
ampoules | 10 ampoule P £584.51
CAUTIONARY AND ADVISORY LABELS 23
Tacrolimus 500 microgram Adoport 0.5mg capsules |
50 capsule P £42.92 DT = £61.88
Tacrolimus 1 mg Adoport 1mg capsules | 50 capsule P £55.69
DT = £80.28 | 100 capsule P £111.36
Tacrolimus 5 mg Adoport 5mg capsules | 50 capsule P £205.74
▶ Prograf (Astellas Pharma Ltd)
Tacrolimus 500 microgram Prograf 500microgram capsules | 50 capsule P £61.88 DT = £61.88
Tacrolimus 1 mg Prograf 1mg capsules | 50 capsule P £80.28
DT = £80.28 | 100 capsule P £160.54
Tacrolimus 5 mg Prograf 5mg capsules | 50 capsule P £296.58
BNF 78 Immune system disorders and transplantation 843
Immune system and malignant disease
IMMUNOSUPPRESSANTS › MONOCLONAL
l DRUG ACTION Canakinumab is a recombinant human
monoclonal antibody that selectively inhibits interleukin1 beta receptor binding.
Gouty arthritis [in patients whose condition has not
responded adequately to treatment with NSAIDs or
colchicine, or in those with contra-indications or
intolerances to them, and in whom repeated courses of
corticosteroids are inappropriate]
▶ Adult: 150 mg for 1 dose, in patients who respond, dose
may be repeated after at least 12 weeks if symptoms
recur, to be administered to the upper thigh, abdomen,
Cryopyrin-associated periodic syndromes (specialist use
▶ Adult (body-weight 41 kg and above): 150 mg every
8 weeks, to be administered to the upper thigh,
abdomen, upper arm or buttocks, additional doses may
be considered if clinical response not achieved within
7 days—consult product literature
Tumour necrosis factor receptor associated periodic
syndrome (specialist use only)| Hyperimmunoglobulin D
syndrome (specialist use only)| Familial Mediterranean
▶ Adult (body-weight 41 kg and above): 150 mg every
4 weeks, to be administered to the upper thigh,
abdomen, upper arm or buttocks, a second dose may be
considered if clinical response not achieved within
7 days—consult product literature
Still’s disease (specialist use only)
▶ Adult: 4 mg/kg every 4 weeks (max. per dose 300 mg),
to be administered to the upper thigh, abdomen, upper
l CONTRA-INDICATIONS Active infection . leucopenia . neutropenia
l CAUTIONS History of recurrent infection . latent and active
tuberculosis . predisposition to infection
▶ Vaccinations Patients should receive all recommended
vaccinations (including pneumococcal and inactivated
influenza vaccine) before starting treatment; avoid live
vaccines unless potential benefit outweighs risk—consult
product literature for further information.
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Uncommon Gastrooesophageal reflux disease
l CONCEPTION AND CONTRACEPTION Effective
contraception required during treatment and for up to
l PREGNANCY Manufacturer advises avoid unless potential
l BREAST FEEDING Consider if benefit outweighs risk—not
known if present in human milk.
l RENAL IMPAIRMENT Limited information available but
manufacturer advises no dose adjustment required.
l PRE-TREATMENT SCREENING Patients should be evaluated
for latent and active tuberculosis before starting
▶ Manufacturer advises monitor full blood count including
neutrophil count before starting treatment, 1–2 months
after starting treatment, and periodically thereafter.
▶ Manufacturer advises monitor for signs and symptoms of
infection (including tuberculosis) during and after
l HANDLING AND STORAGE Manufacturer advises store in a
l PATIENT AND CARER ADVICE Manufacturer advises
patients and carers should be instructed to seek medical
advice if signs or symptoms suggestive of tuberculosis
(including persistent cough, weight loss and subfebrile
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of dizziness
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Ilaris (Novartis Pharmaceuticals UK Ltd)
Canakinumab 150 mg per 1 ml Ilaris 150mg/1ml solution for
injection vials | 1 vial P £9,927.80
IMMUNOSUPPRESSANTS › MONOCLONAL
l DRUG ACTION Basiliximab is a monoclonal antibody that
acts as an interleukin-2 receptor antagonist and prevents
Prophylaxis of acute rejection in allogeneic renal
transplantation used in combination with ciclosporin
and corticosteroid-containing immunosuppression
regimens (specialist use only)
▶ BY INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION
▶ Adult: Initially 20 mg, administered within 2 hours
before transplant surgery, followed by 20 mg after
4 days, dose to be administered after surgery, withhold
second dose if severe hypersensitivity or graft loss
l CAUTIONS Off-label use in cardiac transplantation—
increased risk of serious cardiac side-effects
l INTERACTIONS → Appendix 1: monoclonal antibodies
infarction . nausea . pain . peripheral oedema . post
l CONCEPTION AND CONTRACEPTION Adequate
contraception must be used during treatment and for
l PREGNANCY Manufacturer advises avoid—no information
l BREAST FEEDING Manufacturer advises avoid—no
l DIRECTIONS FOR ADMINISTRATION For intravenous infusion
(Simulect ®) give intermittently in Glucose 5% or Sodium
844 Immune system disorders and transplantation BNF 78
Immune system and malignant disease
chloride 0.9%; reconstitute 10 mg with 2.5 mL water for
injections then dilute to at least 25 mL with infusion fluid;
reconstitute 20 mg with 5 mL water for injections then
dilute to at least 50 mL with infusion fluid; give over 20-
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Immunosuppressive therapy for kidney transplant in adults
Basiliximab, when used as part of an immunosuppressive
regimen that includes a calcineurin inhibitor, is
recommended as an initial option to prevent organ
rejection in adults having a kidney transplant. The use of
basiliximab with tacrolimus is outside the terms of the
marketing authorisation. If this combination is prescribed,
the prescriber should follow relevant professional
guidance, taking full responsibility for the decision.
Informed consent should be obtained and documented.
Patients whose treatment was started within the NHS
before this guidance was published should have the option
to continue treatment, without change to their funding
arrangements, until they and their NHS clinician consider
www.nice.org.uk/guidance/TA481
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder and solvent for solution for injection
▶ Simulect (Novartis Pharmaceuticals UK Ltd)
Basiliximab 10 mg Simulect 10mg powder and solvent for solution
for injection vials | 1 vial P £758.69 (Hospital only)
Basiliximab 20 mg Simulect 20mg powder and solvent for solution
for injection vials | 1 vial P £842.38 (Hospital only)
degree of disease activity despite standard therapy
▶ Adult: 10 mg/kg every 2 weeks for 3 doses, then
10 mg/kg every 4 weeks, review treatment if no
MHRA/CHM ADVICE: BELIMUMAB (BENLYSTA ®): INCREASED RISK
OF SERIOUS PSYCHIATRIC EVENTS SEEN IN CLINICAL TRIALS
Clinical trials show an increased risk of depression,
suicidal ideation or behaviour, or self-injury in patients
with systemic lupus erythematosus on belimumab.
Healthcare professionals should assess patients for these
risks before starting treatment, monitor for new or
worsening signs of these risks during treatment, and
advise patients to seek immediate medical attention if
new or worsening symptoms occur.
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Uncommon Angioedema . skin reactions
▶ Frequency not known Progressive multifocal
leukoencephalopathy (PML). self-injurious behaviour. suicidal tendencies . vomiting
SIDE-EFFECTS, FURTHER INFORMATION Infusion-related
side-effects are reported commonly, including severe or
life-threatening hypersensitivity and infusion reactions.
Premedication with an antihistamine, with or without an
antipyretic may be considered.
l CONCEPTION AND CONTRACEPTION Manufacturer advises
adequate contraception during treatment and for at least
l PREGNANCY Avoid unless essential.
l BREAST FEEDING Avoid—present in milk in animal studies.
l RENAL IMPAIRMENT Caution in severe impairment—no
l MONITORING REQUIREMENTS Delay in the onset of acute
hypersensitivity reactions has been observed; patients
should remain under clinical supervision for several hours
following at least the first 2 infusions.
l DIRECTIONS FOR ADMINISTRATION For intravenous infusion
(Benlysta ®), give intermittently in Sodium chloride 0.9%;
reconstitute with water for injections (120 mg in 1.5 mL,
400 mg in 4.8 mL) to produce a solution containing
80 mg/mL; gently swirl vial for 60 seconds, then allow to
stand; swirl vial (without shaking) for 60 seconds every
5 minutes until dissolved; dilute requisite dose with
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