SOT therapeutics

Question 1

What are the benefits to using combination therapies?

Answer 1

Reduced need for steroid use
Reduced dose of a single agent
Better outcomes

Question 2

What determines the combination of immunosuppressants used?

Answer 2

Patient characteristics including whether they are higher immunogenic risk in addition to side effect profile and co-morbidities

Type of transplant the patient has undergone

Question 3

When are induction immunosuppressants started?

Answer 3

Depending on the type of transplant they can be initiated before the transplant and then carried on during the procedure (operation)
Or started during the procedure and carried on afterwards.

Question 4

When is the risk of transplant rejection greatest?

Answer 4

The risk is highest at the point of transplant and therefore immunosuppression must be the greatest then.
This means that the number of drugs and the doses of immunosuppressants are greatest then and then gradually reduced, however this is dependent upon the patient.

Question 5

Using the example of an intestinal transplant what medications would you expect to see at induction.

Answer 5

At induction (surgery):
Alemtuzumab s/c with required pre-meds due to cytokine release syndrome (paracetamol, chlorphenamine, steroids)

Methylprednisolone IV to oral with an intended end date

Calcineurin inhibitor e.g immediate release Prograf (Tacrolimus)

Post-transplant:
Azathioprine or Mycophenolate

Overall patient ends up on 3 immunosuppressive agents (Methyl prednisolone will be stopped)

Question 6

Using the example of an renal transplant what medications would you expect to see at induction.

Answer 6

As pre-med/induction:
Mycophenolate
Methylprednisolone IV
Basiliximab IV once returned to the ward

Another dose of Basiliximab is given at Day 4 or according to policy

If the patient is at intermediate or high immunogenic risk though (previous transplant and rejection, previous blood transfusion, or antibodies against HLA) Alemutuzumab which is more potent should be used instead of Basiliximab

Question 7

What medications would a post-renal transplant patient receive on Day 1?

Answer 7

Prednisolone 20mg OD, to be reduced over time
Advagraf (MR Tacrolimus) 0.15mg/kg OD
Mycophenolate Mofetil (initiated after Basiliximab 750mg BD - better outcome for patient and graft in MMF use

Question 8

What happens to a patient’s pre-transplant medications once having had a transplant?

Answer 8

Patient’s renal function will be monitored closely during this time, and hopefully as the transplant begins to work previous medications can eventually be stopped.
However they should be reviewed closely

Question 9

What other considerations regarding medication need to be considered in a post-transplant patient?

Answer 9

Increased risk of infection associated with high immunosuppressive use.
Due to a suppressed immune system, patient is at risk of opportunistic and reactivation of latent infections.

Question 10

What is Pneumocystis Jjirovecii?

Answer 10

Is a fungal infection that most commonly affects the immunocompromised and, in some cases, can be severely life-threatening.
It is transmitted person to person by the airborne route.

Question 11

Who is at most risk of Pneumocystis Jjirovecii?

Answer 11

Typically, patients at risk are those with underlying disease states that alter host immunity, such as cancer, HIV, transplant recipients, or those taking immunosuppressive therapies and medications.

Question 12

What are some of the symptoms of Pneumocystis Jjirovecii?

Answer 12

Patients presenting with Pneumocystis Jjirovecii may present with signs of fever, cough, dyspnea, and, in severe cases, respiratory failure.

Question 13

What are the consequences of a Pneumocystis Jjirovecii infection in a transplant patient?

Answer 13

Can lead to a loss of graft function and can be fatal

Question 14

What is the appropriate prophylaxis management of PCP?

Answer 14

6-month prophylaxis dose of Co-trimoxazole

Prophylaxis dose is (adult):
960 mg once daily, reduced if not tolerated to 480 mg once daily, alternatively 960 mg once daily on alternate days

Question 15

What are the therapeutic and toxic monitoring parameters for Co-trimoxazole?

Answer 15

Therapeutic:
Absence of PCP infection

Toxic:
Headache
U & Es - hyperkalaemia
Rash
N&D

Less common:
LFTs (hepatic necrosis)
Skin (life threatening skin and cutaneous adverse effects i.e. Stevens-Johnsons syndrome)
FBC (blood dyscrasias)

Question 16

What is the prophylaxis used for the prevention of invasive fungal infections in immunosuppressed transplant patients?

Answer 16

Nystatin which should be used for 4 weeks post-transplant

Question 17

What are the therapeutic and toxic monitoring parameters for Nystatin?

Answer 17

Therapeutic:
No evidence of oral or GI candida

Toxic:
Usually well tolerated
Higher doses can lead to nausea, vomiting or diarrhoea

Question 18

When is prophylaxis of Tuberculosis given?

Answer 18

The patient’s characteristics are used to determine their risk for example where they are from, if they have latent TB or there is a possibility of them having contact with it.

Question 19

What is the prophylaxis of TB which is given?

Answer 19

The standard regimen for treatment of latent TB infection is nine months isoniazid, also known as isoniazid prophylaxis therapy (IPT) with pyrodoxine.

Question 20

What is Cytomegalovirus?

Answer 20

Cytomegalovirus is a common infection and is related closely to chickenpox and herpes simplex.
In patients with an uncompromised immune system the virus is not usually a problem.
Patients can present with flu-like symptoms or are asymptomatic for 1-2 weeks until the virus becomes dormant.

Question 21

How is Cytomegalovirus transmitted?

Answer 21

By contact with bodily fluids when the virus is active.

Question 22

What happens when CMV becomes dormant in a patient?

Answer 22

The patient is then classified as IgG seropositive (they now contain antibodies against CMV).

Question 23

What is the concern about CMV for a transplant patient?

Answer 23

The concern is:
Either due to high levels of immunosuppression the dormant virus becomes reactivated (are sero-positive)
Or a patient that is sero-negative for CMV is transplanted with an organ that is CMV positive

Both patients will receive prophylaxis

Question 24

What is the CMV prophylaxis for transplant patients?

Answer 24

Valganciclovir for 3-6 months
Dosing is based on renal function

Question 25

What are the therapeutic and toxic monitoring parameters for Valganciclovir?

Answer 25

Therapeutic:
Lack of CMV infection

Toxic:
RF
Hb (anaemia)
FBC (neutropenia, leukopenia, thrombocytopenia, pancytopenia)

Contraception is required on this medication

Question 26

What are some of the common side effects of Valganciclovir?

Answer 26

Diarrhoea
N&V
Dermatitis,
Cough
Headache
Loss of appetite
Infection

Question 27

What do all renal transplant patients receive relating to immobility?

Answer 27

All patients receive DVT prophylaxis which is usually low molecular weight heparin.
This is also due to the risk of renal vein thrombosis.

Question 28

What are the dosing regimen for LMWH?

Answer 28

Dosing is based on weight and renal function, usually give a lower dose to a post-transplant patient initially and then titrate according to improvement in renal function.

CrCl <20mL/min:
Dalteparin 2500IU OD s/c

Then:
Dalteparin 5000IU OD s/c

Question 29

What are the therapeutic and toxic monitoring parameters for Dalteparin?

Answer 29

Therapeutic:
Anti-Xa assay
Lack of post-surgical clot

Toxic:
Platelets - thrombocytopaenia [ > 5days]
K+ - hyperkalaemia
Signs of bleeding - bruising - haematuria – haematemesis – monitor for risk associated
Renal function - eGFR, CrCl
Weight

Question 30

When should LMWH be stopped?

Answer 30

When platelets reach 50 however overall trend should be assessed

Question 31

What is the management of the prophylaxis of renal vein thrombosis?

Answer 31

Lifelong 75mg Aspirin OD, which should be initiated after stopping the LMWH at discharge

Question 32

Which drug should be co-prescribed alongside steroid use?

Answer 32

PPI to protect against GI disturbances associated with steroid use

Question 33

What are the therapeutic and toxic monitoring parameters for PPI (Lansoprazole)?

Answer 33

Therapeutic:
No ulcer formation during surgery or whilst taking steroids

Toxic:
U & Es – hypokalaemia, hypomagnesemia
Risk of osteoporosis
LFTs
Rebound acid
Masking symptoms of gastric cancer
GI symptoms – nausea, vomiting, abdominal pain
GI infection – C diff (over 65s?)

Stop when steroid use is finished, but may need to continue if Aspirin 75mg OD is started for renal vein thrombosis

Question 34

What is a key interaction of PPIs with another transplant medication?

Answer 34

There is an interaction with tacrolimus (metabolised by 3A4 and 2C19 so they compete for metabolism). This may cause an increase in serum Tacrolimus levels, should monitor closely.

Question 35

Which medication is used in the treatment of pain?

Answer 35

Paracetamol
Fentanyl PCA (patient controlled analgesia)

Question 36

What are the therapeutic and toxic monitoring parameters for Paracetamol?

Answer 36

Therapeutic:
Pain relief

Toxic:
Weight
Maximum dose counselling
Alcohol
Malnutrition
LFT
FBC

Question 37

What are the therapeutic and toxic monitoring parameters for Fentanyl?

Answer 37

Therapeutic:

Toxic:
Constipation
Drowsiness
Flushing
N&V
Skin reactions
Palpitations
Respiratory rate depression

Question 38

What other risks are associated with immunosuppression?

Answer 38

Increased risk of malignancy, particularly skin cancers.
Therefore would inform the patient to avoid/limit UV sun exposure
Increased risk of lymphoproliferative disease.

This is because there is reduced immune surveillance and reduced response to cancer causing infections (perhaps why cervical screening is required).
Immunosuppression increases the carcinogenic risk of certain cancer risk factors