260
P A R T 3
Drugs acting on the immune system
and to enhance the inflammatory response. Of interest,
interferon gamma-1b also acts like an interleukin, stim-
ulating phagocytes to be more aggressive. See Table 17.1
for usual indications for each interferon.
Pharmacokinetics
The interferons are generally well absorbed after sub
cutaneous or intramuscular injection. They have a rapid
onset of action and peak within 3 to 8 hours, with a
half-life ranging from 3 to 8 hours, with the exception
of interferon beta-1a, which has an onset of action of
12 hours and reaches peak levels in 48 hours, with a
half-life of 10 hours. They are broken down in the liver
and kidneys and seem to be excreted primarily through
the kidneys.
Contraindications and cautions
The use of interferons is contraindicated in the presence
of known allergy to any interferon or product compo-
nents. Many of the interferons are teratogenic in animals
and therefore should not be used during pregnancy. Use
of barrier contraceptives is advised for women of child-
bearing age. It is not known whether these drugs cross
into breast milk, but because of the potential adverse
effects on the baby, it is advised that the drugs not be used
during breastfeeding unless the benefits to the mother
clearly outweigh any risks to the baby
.
Caution should
be used in the presence of known cardiac disease
because
hypertension and arrhythmias have been reported with
the use of these drugs
; with myelosuppression
because
these drugs may further suppress the bone marrow
; and
with central nervous system (CNS) dysfunction of any
kind
because of the potential for CNS depression and
personality changes that have been reported.
BOX 17.1
Drug therapy across the lifespan
Immune modulators
CHILDREN
Most of the drugs that affect the immune system are
not recommended for use in children or have not been
tested in children.The exceptions—interferon alfa-2b,
azathioprine, cyclosporin, tacrolimus and palivizumab—
should be used cautiously, monitoring the child frequently
for infection, GI, renal, haematological or CNS effects.
The immune suppressants (azathioprine, cyclosporin,
and tacrolimus) are usually needed in higher doses for
children than for adults to achieve the same therapeutic
effect.
Protecting the child from infection and injury is a very
important part of the care of a child taking an immune
modulator.This can be a great challenge with an active
child.
ADULTS
Both the adult who is receiving a parenteral immune
modulator and a significant other should learn the proper
technique for injection, disposal of needles and special
storage precautions for the drug. It is important to stress
ways to avoid exposure to infection and injury to prevent
further complications.The person should be encouraged to
seek regular follow-up and medical care.
PREGNANCY AND BREASTFEEDING
Immune modulators are contraindicated during pregnancy
and breastfeeding because of the potential for adverse
effects on the fetus or neonate and complications for the
mother. Women of childbearing age should be advised to
use barrier contraceptives while taking these drugs and,
if breastfeeding, should be counselled to find another
method of feeding the baby. Some of these drugs impair
fertility, and the person should be advised of this fact
before taking the drug.
OLDER ADULTS
Older people may be more susceptible to the effects of the
immune modulators, partly because the ageing immune
system is less efficient and less responsive.
These people need to be monitored closely for infection,
GI, renal, hepatic and CNS effects. Baseline renal and liver
function tests can help to determine whether a decreased
dosage will be needed before beginning therapy.
Because these people are more susceptible to infection,
they need to receive extensive teaching about ways to
avoid infection and injury.
Immune modulators and pregnancy
Generally, immune modulators are contraindicated
for use during pregnancy and breastfeeding, largely
because these drugs have been associated with fetal
abnormalities, increased maternal and fetal infections,
and suppressed immune responses in breastfeeding
babies. Women should be informed of the risk of using
these drugs during pregnancy and receive counselling
in the use of barrier contraceptives. (The use of barrier
contraceptives is advised because the effects of oral
contraceptives may be altered by liver changes or by
changes in the body’s immune response, potentially
resulting in unexpected pregnancy.)
If a woman taking immune modulators becomes
pregnant or decides that she wants to become pregnant,
she should discuss this with her healthcare provider
and review the risks associated with use of the drug or
drugs being taken.The monoclonal antibodies should be
used with caution during pregnancy and breastfeeding.
Because long-term studies of most of these drugs are not
yet available, it may be prudent to advise women taking
these drugs to avoid pregnancy if possible.
Gender considerations
BOX 17.2
