Shared care protocol


Clinical indication: for use in transplant patients
Version 1: May 2008
due for review: May 2010

Tacrolimus is a macrolide immunosuppressant which suppresses T-cell activation, T-
helper-cell-dependent B-cell proliferation, and the production of lymphokines such as
interleukins -2 and -3. This mode of action is similar to that of ciclosporin but
tacrolimus is more potent.
Shared Care
As outlined in the NHS circular 1992 (Gen 11) a consultant may seek the GPs
involvement in prescribing for a patient where there is a shared care agreement. This
leaflet provides information on tacrolimus treatment and guidelines for the shared-
care of tacrolimus therapy between the hospital consultant and the GP concerned.
Indication for Therapy
Tacrolimus is licensed for immunosuppression in kidney and liver transplantation and
for the treatment of resistant rejection. It may also be used in patients with intolerable
side effects to ciclosporin.
Some patients will start tacrolimus in the early post transplant period and will have
undergone stabilisation and be receiving maintenance doses before referral to the GP
(approx. 14-21 days post transplant).
Patients who are transferred from ciclosporin to tacrolimus whilst attending the
outpatient clinic will only be referred to the GP once the patient has been stabilised on
The hospital pharmacy will provide in-patients with at least a 7-day supply of
medication on discharge and outpatients until stabilised.
Recommended Dosage and Administration
Tacrolimus (Prograf) will be used only as the preparation for two divide doses
The initial tacrolimus dosage is 0.1 to 0.2mg/kg/day, given in two divided doses at
10am and 10pm.
The use of tacrolimus (Advagraf) will be used as the once daily preparation. This will
only be used under the direct supervision of the hospital consultant.
Tacrolimus trough blood concentrations require to be monitored with a target range of
5-15 nanograms/ml. The target blood level for an individual patient will depend on
the time since transplant, the history of rejection and side effects.
Tacrolimus should be taken on an empty stomach, either one hour before or two hours
after a meal.
The combined administration of ciclosporin and tacrolimus is not recommended as
tacrolimus may increase the half-life of ciclosporin.
Shared Care Protocol and information for GPs - Tacrolimus for use in transplant patients

A self medication programme is in operation on the Transplant Unit and all suitable
patients are encouraged to self medicate soon after the operation in early preparation
for their discharge. The pharmacist responsible for the Transplant Unit undertakes to
counsel all post transplant patients on their medication and to provide patient
information leaflets on the medicines commonly prescribed.
Tacrolimus is available as 500mcg (yellow), 1mg (white) and 5mg (greyish-red)
capsules. The brand name is Prograf
The estimated cost per patient year varies from £1240-£4584 depending on the dose.
(Dose range used 2mg to 10mg per day).
Precautions and Contra-Indications
Tacrolimus is contra-indicated in pregnancy.
As it is not known to what extent tacrolimus may influence the efficacy of oral
contraceptives, it is generally recommended that other forms of contraception should
be used. However, as tacrolimus inhibits ethinyloestradiol metabolism in vitro it is
suggested that the efficacy of oral contraceptives might be unaffected.
Shared Care Responsibilities
Aspects of care for which the Hospital Consultant is responsible

 Clinic appointments on a Tuesdays and also dependent on time from  Monitoring blood pressure, weight, liver function tests and renal function with  Blood level monitoring and adjustment of tacrolimus dosage. Blood level monitoring will be done on a 3 monthly bases in the first year post renal transplantation and their after between 3 and 6 monthly depending on the stability of the renal transplant patient. If a significant dose change is necessary then this is communicated to the patient immediately by telephone with additional written confirmation. The letter informing of the dose change is also sent to the GP. GP will also be able to check routine tacrolimus dosage for those patients with access t
Aspects of care for which the General Practitioner is responsible
 Prescribing of maintenance tacrolimus therapy (but not dosage adjustment).
 Adverse drug reaction/interaction monitoring and liaison with the hospital
consultant regarding any complications of treatment.
Side Effects
As with all immunosuppressants tacrolimus increases susceptibility to infection,
especially severe chicken pox. Additionally, vaccinations may not give full
protection against disease and live vaccines need to be avoided.
The most frequent side effects seen with tacrolimus include tremor, headache,
paraesthesia and abnormal kidney function. Less commonly, diarrhoea, hypertension,
hyperglycaemia, and hyperkalaemia have been seen.
Tacrolimus may cause visual and neurological disturbances and affected patients
should be warned not to drive a car or operate dangerous machinery.
Shared Care Protocol and information for GPs - Tacrolimus for use in transplant patients
Great care should be taken when prescribing other nephrotoxic drugs, e.g.
trimethoprim, and non-steroidals. When tacrolimus is used concomitantly with
potentially neurotoxic drugs, e.g. acyclovir, the neurotoxicity of these drugs may be
ACE inhibitors, potassium sparing diuretics and salt substitutes may increase the risk
of hyperkalaemia.
Effects on Drug Blood Levels
Tacrolimus is extensively metabolised in the liver via the cytochrome P-450 enzyme
system and may have an inducing or inhibitory effect on these enzymes. Therefore
care should be taken when co-administering other drugs known to be metabolised by
this system.
Grapefruit and grapefruit juice contain a compound which may be potentially inhibit
tacrolimus metabolism.
Clinical data on drug interactions are limited. Please refer to the current British National
Formulary and the Summary of Product Characteristics for updated information before
prescribing new medicines.
Drugs which may increase tacrolimus blood levels:

Drugs which may decrease tacrolimus blood levels:
Carbamazepine Phenytoin

Drugs whose metabolism may be inhibited by tacrolimus:
Steroid-based contraceptive agents
Tacrolimus is extensively bound (>98%) to plasma proteins, albumin and
glycoprotein so there is possibility of interaction with other drugs which have a high
affinity to plasma protein, e.g. warfarin.
Concomitant administration of methylprednisolone has been reported to both increase
and decrease tacrolimus levels.
Contact Points
Dr Ahmed's Secretary
Dr Mansy's Secretary
Renal Ambulatory Care
Sunderland Royal Hospital
Version 1: May 2008 - Revision Date: May 2010
This information was prepared by the consultants and pharmacists of the Renal Unit at Sunderland Royal Hospital and the Drug and Therapeutics Committee.



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