SPECIFIC SIDE-EFFECTS
▶With oral useNausea
SIDE-EFFECTS, FURTHER INFORMATIONSide-effects may
require drug withdrawal.
Hypersensitivity reactionsHypersensitivity reactions
(including malaise, dizziness, vomiting, diarrhoea, fever,
rigors, myalgia, arthralgia, rash, hypotension and renal
dysfunction) call for immediate withdrawal.
Neutropenia and thrombocytopeniaNeutropenia is
dose-dependent. Management of neutropenia and
thrombocytopenia requires careful monitoring and dose
adjustment.lALLERGY AND CROSS-SENSITIVITYContra-indicated in
hypersensitivity to mercaptopurine.
lPREGNANCYTransplant patients immunosuppressed with
azathioprine should not discontinue it on becoming
pregnant. However, there have been reports of premature
birth and low birth-weight following exposure to
azathioprine, particularly in combination with
corticosteroids. Spontaneous abortion has been reported
following maternal or paternal exposure. Azathioprine is
teratogenic inanimalstudies. The use of azathioprine
during pregnancy needs to be supervised in specialist
units. Treatment should not generally be initiated during
pregnancy.
lBREAST FEEDINGPresent in milk in low concentration. No
evidence of harm in small studies—use if potential benefit
outweighs risk.
lHEPATIC IMPAIRMENT
Dose adjustmentsReduce dose.
MonitoringMonitor liver function.
lRENAL IMPAIRMENT
Dose adjustmentsReduce dose.
lPRE-TREATMENT SCREENING
Thiopurine methyltransferaseThe enzyme thiopurine
methyltransferase (TPMT) metabolises thiopurine drugs
(azathioprine, mercaptopurine, tioguanine); the risk of
myelosuppression is increased in patients with reduced
activity of the enzyme, particularly for the few individuals
in whom TPMT activity is undetectable. Consider
measuring TPMT activity before starting azathioprine,
mercaptopurine, or tioguanine therapy. Patients with
absent TPMT activity should not receive thiopurine drugs;
those with reduced TPMT activity may be treated under
specialist supervision.
lMONITORING REQUIREMENTS
▶Monitor for toxicity throughout treatment.
▶Monitor full blood count weekly (more frequently with
higher doses or if severe hepatic or renal impairment) for
first 4 weeks (manufacturer advises weekly monitoring for
8 weeks but evidence of practical value unsatisfactory),
thereafter reduce frequency of monitoring to at least every
3 months.
▶Blood tests and monitoring for signs of myelosuppression
are essential in long-term treatment.
lDIRECTIONS FOR ADMINISTRATION
▶With intravenous useConsult local treatment protocol for
details. Forintravenous injection, reconstitute 50 mg with
5 – 15 mL Water for Injections; give over at least 1 minute.
Forintravenous infusion, reconstitute 50 mg with 5 – 15 mL
Water for Injections; dilute requisite dose to a
concentration of 0. 25 – 2. 5 mg/mL in Glucose 5 %orSodium
Chloride 0. 9 %. Intravenous injection is alkaline and very
irritant. Intravenous route should therefore be usedonlyif
oral route not feasible and discontinued as soon as oral
route can be tolerated. To reduce irritationflush line with
infusionfluid.
lPRESCRIBING AND DISPENSING INFORMATIONThe RCPCH
and NPPG recommend that, when a liquid special of
azathioprine is required, the following strength is used:
50 mg/ 5 mL.
lPATIENT AND CARER ADVICE
Medicines for Children leaflet: Azathioprine for inflammatory
bowel diseasewww.medicinesforchildren.org.uk/azathioprine-
inflammatory-bowel-disease- 0
Medicines for Children leaflet: Azathioprine for renal (kidney)
transplantwww.medicinesforchildren.org.uk/azathioprine-
renal-kidney-transplant- 0
Medicines for Children leaflet: Azathioprine for severe atopic
eczemawww.medicinesforchildren.org.uk/azathioprine-severe-
atopic-eczema- 0
Bone marrow suppressionPatients and their carers should be
warned to report immediately any signs or symptoms of
bone marrow suppression e.g. inexplicable bruising or
bleeding, infection.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug. Forms available from special-order
manufacturers include: capsule, oral suspension, oral solution
Tablet
CAUTIONARY AND ADVISORY LABELS 21
▶Azathioprine (Non-proprietary)
Azathioprine 25 mgAzathioprine 25 mg tablets| 28 tabletP
£ 8. 41 DT = £ 1. 30 | 100 tabletP£ 4. 64 – £ 33. 26
Azathioprine 50 mgAzathioprine 50 mg tablets| 56 tabletP
£ 7. 28 DT = £ 2. 20 | 100 tabletP£ 3. 93 – £ 16. 55
▶Azapress(Ennogen Pharma Ltd)
Azathioprine 50 mgAzapress 50 mg tablets| 56 tabletP£ 2. 83
DT = £ 2. 20
▶Imuran(Aspen Pharma Trading Ltd)
Azathioprine 25 mgImuran 25 mg tablets| 100 tabletP£ 10. 99
Azathioprine 50 mgImuran 50 mg tablets| 100 tabletP£ 7. 99
Powder for solution for injection
▶Imuran(Aspen Pharma Trading Ltd)
Azathioprine 50 mgImuran 50 mg powder for solution for injection
vials| 1 vialP£ 15. 38IMMUNOSUPPRESSANTS›CALCINEURIN
INHIBITORS AND RELATED DRUGSCiclosporin 01-Sep-2016
(Cyclosporin)
lDRUG ACTIONCiclosporin inhibits production and release
of lymphokines, thereby suppressing cell-mediated
immune response.lINDICATIONS AND DOSE
Refractory ulcerative colitis
▶BY MOUTH
▶Child 2–17 years:Initially 2 mg/kg twice daily (max. per
dose 5 mg/kg twice daily), dose adjusted according to
blood-ciclosporin concentration and response
▶BY INTRAVENOUS INFUSION
▶Child 3–17 years:Initially 0. 5 – 1 mg/kg twice daily, dose
adjusted according to blood-ciclosporin concentration
and response
Short-term treatment of severe atopic dermatitis 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) usual maximum duration of
8 weeks but may be used for longer under specialist
supervision, if good initial response not achieved
within 2 weeks, increase dose rapidly up to
maximum continued→BNFC 2018 – 2019 Immune system disorders and transplantation 519
Immune system and malignant disease8