C H A P T E R 1 4
Antineoplastic agents
207
Pharmacokinetics
The antineoplastic antibiotics are not absorbed well
from the GI tract. They are given intravenously (IV) or
injected into specific sites. They are metabolised in the
liver and excreted in the urine at various rates. Many
of them have very long half-lives (e.g. 45 hours for
idarubicin; more than 5 days for mitoxantrone). Dauno
rubicin and doxorubicin do not cross the blood–brain
barrier, but they are widely distributed in the body and
are taken up by the heart, lungs, kidneys and spleen.
This can lead to toxic effects in these organs.
Contraindications and cautions
All of these agents are contraindicated for use during
pregnancy and breastfeeding
because of the potential
risk to the fetus and neonate
. Use caution when giving
antineoplastic antibiotics to an individual with a known
allergy to the antibiotic or related antibiotics. Care
is necessary when administering these agents to indi
viduals with the following conditions: bone marrow
suppression,
which is often the index for re-dosing
and dosing levels
; suppressed renal or hepatic function,
which might interfere with the metabolism or excre-
tion of these drugs and often indicates a need to change
the dose
; known GI ulcerations or ulcerative diseases,
which may be exacerbated by the effects of these drugs
;
pulmonary problems with bleomycin or mitomycin,
or cardiac problems with idarubicin or mitoxantrone,
which are specifically toxic to these organ systems.
Adverse effects
Adverse effects frequently encountered with the use of
these antibiotics include bone marrow suppression, with
leucopenia, thrombocytopenia, anaemia and pancyto
penia, secondary to the effects of the drugs on the rapidly
multiplying cells of the bone marrow. Toxic GI effects
include nausea, vomiting, anorexia, diarrhoea and
mucous membrane deterioration, all of which are related
to drug effects on the rapidly multiplying cells of the GI
tract. As with the alkylating agents and antimetabolites,
effects of antineoplastic antibiotics may include renal or
hepatic toxicity, depending on the exact mechanism of
action. Alopecia may also occur. Specific antineoplastic
antibiotics are toxic to the heart and lungs.
Clinically important drug–drug interactions
Antimetabolites that are known to cause hepatic or
renal toxicity should be used with care with any other
drugs known to have the same effect. Drugs that result
in toxicity to the heart or lungs should be used with
caution with any other drugs that produce that particu
lar toxicity. Check for specific drug–drug interactions
for each agent in a nursing drug guide.
TABLE 14.3
DRUGS IN FOCUS Antineoplastic antibiotics (continued)
Drug name
Dosage/route
Usual indications
mitoxantrone (generic)
14 mg/m
2
per day IV every 2 days
Part of combination therapy in the
treatment of adult leukaemias; treatment
of bone pain in advanced prostatic cancer
Special considerations:
severe bone
marrow suppression may occur and limits
dose; alopecia, GI toxicity and congestive
heart failure often occur; avoid direct skin
contact with the drug—use gloves and
goggles; monitor bone marrow activity
and cardiac activity to adjust dose or
discontinue drug as needed
Prototype summary: Doxorubicin
Indications:
To produce regression in acute
lymphoblastic lymphoma, acute myeloblastic
leukaemia, Wilms tumour, neuroblastoma, soft
tissue and bone sarcoma, breast carcinoma,
ovarian carcinoma, thyroid carcinoma, Hodgkin’s
and non-Hodgkin’s lymphomas, bronchogenic
carcinoma; also to treat AIDS-related Kaposi’s
sarcoma.
Actions:
Binds to DNA and inhibits DNA synthesis
in susceptible cells, causing cell death.
Pharmacokinetics:
Route Onset
Peak
Duration
IV Rapid
2 hours
24–36 hours
T
1/2
:
12 minutes, then 3.3 hours, then 29.6 hours;
metabolised in the liver and excreted in the bile,
faeces and urine.
Adverse effects:
Cardiac toxicity, complete but
reversible alopecia, nausea, vomiting, mucositis, red
urine, myelosuppression, fever, chills, rash.
