Drug Summaries – Humza Ibrahim
Chapter 8
Malignant disease
TABLE OF CONTENTS
Table of Contents ......................................................... 1
1 Immune system .................................................... 2
1.1 Antiproliferative immunosuppressants ....... 2
1.1.1 Azathioprine ......................................... 2
1.1.2 Mycophenolate .................................... 2
1.2 Ciclosporin (high risk) .................................. 2
1.2.1 Warning signs ....................................... 3
1.2.2 Monitoring ........................................... 3
1.2.3 Pregnancy............................................. 3
1.2.4 Other points ......................................... 3
1.2.5 Interactions .......................................... 3
1.3 Tacrolimus (high risk) .................................. 3
1.3.1 Warning signs ....................................... 3
1.3.2 Monitoring ........................................... 4
1.3.3 Pregnancy and breastfeeding .............. 4
1.3.4 Other points ......................................... 4
1.3.5 Interactions .......................................... 4
2 Malignant disease ................................................ 4
2.1 Cytotoxic responsive malignancy ................. 4
2.1.1 Guidelines for handling
cytotoxic drugs ..................................................... 4
2.1.2 Safe system requirements ................... 4
2.1.3 Risks of incorrect oral dosing ............... 4
2.1.4 Doses .................................................... 5
2.1.5 Side-effects of cytotoxic drugs ............. 5
2.1.6 Pregnancy and reproductive function . 5
2.2 Vinca alkaloids.............................................. 6
2.3 Methotrexate (high risk) ............................. 6
2.3.1 Warning signs ....................................... 6
2.3.2 Monitoring ........................................... 6
2.3.3 Interactions .......................................... 6
2.3.4 Other points ......................................... 6
2.3.5 Pregnancy and breastfeeding .............. 6
2.4 Tamoxifen .................................................... 6
Chapter 8 – Pg 1
Compiled using the British National Formulary
, Drug Summaries – Humza Ibrahim
1.1.1.3 Pre-treatment screening
Chapter 8 Thiopurine methyltransferase (TPMT) metabolises
thiopurine drugs (azathioprine, mercaptopurine); the
Malignant disease risk of myelosuppression is increased in patients with
reduced activity of the enzyme. TPMT activity should
be measured before starting azathioprine or
1 IMMUNE SYSTEM mercaptopurine. Patients with absent TPMT activity
should not receive thiopurine drugs; those with
Chronic inflammatory and autoimmune diseases, and
reduced TPMT activity need specialist supervision.
organ transplant patients are maintained on drug
regimens, which may include antiproliferative drugs 1.1.2 Mycophenolate
(azathioprine or mycophenolate mofetil), calcineurin Mycophenolate has a more selective mode of action
inhibitors (ciclosporin or tacrolimus), corticosteroids, than azathioprine. It is licensed for the prophylaxis of
or sirolimus. acute rejection in renal, hepatic or cardiac
The use of azathioprine and ciclosporin should not be transplantation when used in combination with
discontinued during pregnancy. The use of these ciclosporin and corticosteroids.
drugs during pregnancy needs to be supervised in 1.1.2.1 Bone marrow suppression
specialist units. Patients should be warned to report immediately any
signs or symptoms of bone marrow suppression e.g.
1.1 ANTIPROLIFERATIVE infection or inexplicable bruising or bleeding.
IMMUNOSUPPRESSANTS 1.1.2.2 Risk of hypogammaglobulinemia or
bronchiectasis
1.1.1 Azathioprine When used in combination with other
Azathioprine is used for transplant recipients and immunosuppressants risk of recurrent infections
auto-immune conditions, it is metabolised to (hypogammaglobulinemia), and respiratory symptoms
mercaptopurine. Doses should be reduced when such as cough and dyspnoea (bronchiectasis)
allopurinol is given concurrently due to risk of bone
1.1.2.3 Red cell aplasia
marrow suppression.
Cases have been reported with azathioprine and with
1.1.1.1 Side effects mycophenolate mofetil; dose reduction or
Red cell aplasia has been reported with azathioprine discontinuation should be considered under specialist
and mycophenolate mofetil; dose reduction or supervision.
discontinuation should be considered under specialist
1.1.2.4 Pregnancy prevention
supervision.
Congenital malformations and spontaneous abortions
Hypersensitivity reactions (including malaise, reported. Exclude pregnancy immediately before and
dizziness, vomiting, diarrhoea, fever, rigors, myalgia, during treatment. Women should use 2 methods of
arthralgia, rash, hypotension and interstitial effective contraception during treatment, and for 6
nephritis—calling for immediate withdrawal weeks after discontinuation. Men and their partners
should both use contraception during treatment and
Patients should be warned to report immediately any for at least 90 days after discontinuation.
signs or symptoms of bone marrow suppression e.g.
inexplicable bruising or bleeding, infection.
Nausea, vomiting, and diarrhoea may occur during
1.2 CICLOSPORIN (HIGH RISK)
early stages of treatment, in rheumatoid arthritis Ciclosporin a calcineurin inhibitor, is a potent
treatment can be discontinued if this occurs. immunosuppressant which is virtually non-myelotoxic
but markedly nephrotoxic.
1.1.1.2 Monitoring requirements
Loading doses may be required
Full blood count for 4 weeks then every 3 months;
monitor toxicity throughout treatment; blood tests
and monitoring for signs of myelosuppression in long-
term treatment
Chapter 8 – Pg 2
Compiled using the British National Formulary
Chapter 8
Malignant disease
TABLE OF CONTENTS
Table of Contents ......................................................... 1
1 Immune system .................................................... 2
1.1 Antiproliferative immunosuppressants ....... 2
1.1.1 Azathioprine ......................................... 2
1.1.2 Mycophenolate .................................... 2
1.2 Ciclosporin (high risk) .................................. 2
1.2.1 Warning signs ....................................... 3
1.2.2 Monitoring ........................................... 3
1.2.3 Pregnancy............................................. 3
1.2.4 Other points ......................................... 3
1.2.5 Interactions .......................................... 3
1.3 Tacrolimus (high risk) .................................. 3
1.3.1 Warning signs ....................................... 3
1.3.2 Monitoring ........................................... 4
1.3.3 Pregnancy and breastfeeding .............. 4
1.3.4 Other points ......................................... 4
1.3.5 Interactions .......................................... 4
2 Malignant disease ................................................ 4
2.1 Cytotoxic responsive malignancy ................. 4
2.1.1 Guidelines for handling
cytotoxic drugs ..................................................... 4
2.1.2 Safe system requirements ................... 4
2.1.3 Risks of incorrect oral dosing ............... 4
2.1.4 Doses .................................................... 5
2.1.5 Side-effects of cytotoxic drugs ............. 5
2.1.6 Pregnancy and reproductive function . 5
2.2 Vinca alkaloids.............................................. 6
2.3 Methotrexate (high risk) ............................. 6
2.3.1 Warning signs ....................................... 6
2.3.2 Monitoring ........................................... 6
2.3.3 Interactions .......................................... 6
2.3.4 Other points ......................................... 6
2.3.5 Pregnancy and breastfeeding .............. 6
2.4 Tamoxifen .................................................... 6
Chapter 8 – Pg 1
Compiled using the British National Formulary
, Drug Summaries – Humza Ibrahim
1.1.1.3 Pre-treatment screening
Chapter 8 Thiopurine methyltransferase (TPMT) metabolises
thiopurine drugs (azathioprine, mercaptopurine); the
Malignant disease risk of myelosuppression is increased in patients with
reduced activity of the enzyme. TPMT activity should
be measured before starting azathioprine or
1 IMMUNE SYSTEM mercaptopurine. Patients with absent TPMT activity
should not receive thiopurine drugs; those with
Chronic inflammatory and autoimmune diseases, and
reduced TPMT activity need specialist supervision.
organ transplant patients are maintained on drug
regimens, which may include antiproliferative drugs 1.1.2 Mycophenolate
(azathioprine or mycophenolate mofetil), calcineurin Mycophenolate has a more selective mode of action
inhibitors (ciclosporin or tacrolimus), corticosteroids, than azathioprine. It is licensed for the prophylaxis of
or sirolimus. acute rejection in renal, hepatic or cardiac
The use of azathioprine and ciclosporin should not be transplantation when used in combination with
discontinued during pregnancy. The use of these ciclosporin and corticosteroids.
drugs during pregnancy needs to be supervised in 1.1.2.1 Bone marrow suppression
specialist units. Patients should be warned to report immediately any
signs or symptoms of bone marrow suppression e.g.
1.1 ANTIPROLIFERATIVE infection or inexplicable bruising or bleeding.
IMMUNOSUPPRESSANTS 1.1.2.2 Risk of hypogammaglobulinemia or
bronchiectasis
1.1.1 Azathioprine When used in combination with other
Azathioprine is used for transplant recipients and immunosuppressants risk of recurrent infections
auto-immune conditions, it is metabolised to (hypogammaglobulinemia), and respiratory symptoms
mercaptopurine. Doses should be reduced when such as cough and dyspnoea (bronchiectasis)
allopurinol is given concurrently due to risk of bone
1.1.2.3 Red cell aplasia
marrow suppression.
Cases have been reported with azathioprine and with
1.1.1.1 Side effects mycophenolate mofetil; dose reduction or
Red cell aplasia has been reported with azathioprine discontinuation should be considered under specialist
and mycophenolate mofetil; dose reduction or supervision.
discontinuation should be considered under specialist
1.1.2.4 Pregnancy prevention
supervision.
Congenital malformations and spontaneous abortions
Hypersensitivity reactions (including malaise, reported. Exclude pregnancy immediately before and
dizziness, vomiting, diarrhoea, fever, rigors, myalgia, during treatment. Women should use 2 methods of
arthralgia, rash, hypotension and interstitial effective contraception during treatment, and for 6
nephritis—calling for immediate withdrawal weeks after discontinuation. Men and their partners
should both use contraception during treatment and
Patients should be warned to report immediately any for at least 90 days after discontinuation.
signs or symptoms of bone marrow suppression e.g.
inexplicable bruising or bleeding, infection.
Nausea, vomiting, and diarrhoea may occur during
1.2 CICLOSPORIN (HIGH RISK)
early stages of treatment, in rheumatoid arthritis Ciclosporin a calcineurin inhibitor, is a potent
treatment can be discontinued if this occurs. immunosuppressant which is virtually non-myelotoxic
but markedly nephrotoxic.
1.1.1.2 Monitoring requirements
Loading doses may be required
Full blood count for 4 weeks then every 3 months;
monitor toxicity throughout treatment; blood tests
and monitoring for signs of myelosuppression in long-
term treatment
Chapter 8 – Pg 2
Compiled using the British National Formulary
