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P A R T 3
Drugs acting on the immune system
Clinically important drug–drug interactions
There is an increased risk of toxicity if these drugs
are combined with other drugs that are hepatotoxic
or nephrotoxic. Extreme care should be used if such
combinations are necessary. Other reported drug–drug
interactions are drug specific; consult a drug guide or
drug handbook.
I
nterleukin
-
receptor antagonist
An interleukin-receptor antagonist works to block
the activity of the interleukins that are released in an
inflammatory or immune response. The only available
interleukin receptor antagonist is anakinra (
Kineret
).
See Table 17.2 for additional information about this
drug.
Therapeutic actions and indications
Anakinra specifically antagonises human interleukin-1
receptors, blocking the activity of interleukin-1. Inter-
leukin-1 levels are elevated in response to inflammation
or immune reactions and are thought to be responsible
for the degradation of cartilage that occurs in rheum
atoid arthritis. Anakinra is used to reduce the signs and
symptoms of moderately to severely active rheumatoid
arthritis in people 18 years of age and older who have
not responded to the traditional anti-rheumatic drugs.
As one of the most common chronic conditions in
Australia, arthritis is one of the Australian government’s
nine National Health Priority Areas. Data from the
2007–08 National Health Survey suggest that 428,000
Australians are affected by rheumatoid arthritis. For
more information on arthritis, see
/
arthritis-and-musculoskeletal-conditions.
Pharmacokinetics
The recommended dosage is 100 mg/day by subcutane-
ous injection. Anakinra is administered by subcutaneous
injection and is absorbed slowly, reaching peak effects in
3 to 7 hours. It is metabolised in the tissues with a 4- to
6-hour half-life and is excreted in the urine.
Contraindications and cautions
Anakinra is contraindicated with any known allergy to
E. coli
–produced products or to anakinra itself. It should
be used with caution during pregnancy and breastfeed-
ing
because the drug may cross the placenta and enter
breast milk
. It is also used cautiously in people with renal
impairment, immunosuppression or any active infection
because these could be exacerbated by the effects of the
drug
. There is an increased risk of infection whenever
this drug is used, and the person needs to be protected
from exposure to infections and monitored closely after
any invasive procedures. Immunisations cannot be given
while the person is on this drug.
Adverse effects
Headache, sinusitis, nausea, diarrhoea, upper respira-
tory and other infections and injection-site reactions are
among the most common adverse effects.
Clinically important drug–drug interactions
People who are also receiving etanercept (
Enbrel
) must
be monitored very closely because severe and even
life-threatening infections have occurred. Anakinra
should not be combined with abatacept because of the
potential for serious infections.
M
onoclonal antibodies
Antibodies that attach to specific receptor sites are
being developed to respond to very specific situations.
Every year, several new monoclonal antibodies are
marketed, showing the rapid pace with which these
agents are being developed and approved for clinical
use. Monoclonal antibodies include adalimumab
(
Humira
), alemtuzumab (
MabCampath
), basiliximab
(
Simulect
), bevacizumab (
Avastin
), certolizumab pegol
(
Cimzia
), cetuximab (
Erbitux
), erlotinib (
Tarceva
), goli-
mumab (
Simponi
), infliximab (
Remicade
), natalizumab
(
Tysabri
), omalizumab (
Xolair
), palivizumab (
Synagis
),
panitumumab (
Vectibix
),
rituximab (
Mabthera
), tocili-
zumab (
Actemra
), trastuzumab (
Herceptin, Kadcyla
)
and ustekinumab (
Stelara
).
Therapeutic actions and indications
Adalimumab, certolizumab pegol, golimumab and
infliximab are antibodies specific for human tumour
necrosis factor. They keep the inflammatory reaction in
check by reacting with and deactivating the free-floating
tumour necrosis factor released by active leucocytes.
Alemtuzumab is an antibody specific for lympho-
cytereceptor sites.
Basiliximab is specific to interleukin-2 receptor sites
on activated T lymphocytes; it reacts with those sites
and blocks cellular response to allograft transplants.
Cetuximab is an antibody specific to epidermal
growth factor receptor sites. Trastuzumab also reacts
with human epidermal growth factor receptor 2 (HER2),
a genetic defect that is seen in certain metastatic breast
cancers. It is used in the treatment of metastatic breast
cancer in tumours that over-express HER2.
Erlotinib, bevacizumab and panitumumab are effec-
tive against specific malignant receptor sites.
