encouraged to seek regular follow-up and
medical care.
Chapter 17: Immune Modulators
Immune Modulators
- Are used to modify the actions of the
immune system.
Drug Therapy Across the Lifespan
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, raxibacumab, cyclosporine,
tacrolimus, and palivizumab—should be
used cautiously, monitoring the child
frequently for infection, GI, renal,
hematological, or CNS effects.
- The immune suppressants (azathioprine,
cyclosporine, 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 patient 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 patient should be
- Immune modulators are contraindicated
during pregnancy and lactation 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 counseled to find another method
of feeding the baby. Some of these drugs
impair fertility, and the patient should be
advised of this fact before taking the drug.
Other Adults
Older patients may be more susceptible to the
effects of the immune modulators, partly because
the aging immune system is less efficient and less
responsive.
- These patients 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 patients are more susceptible
to infection, they need to receive extensive
teaching about ways to avoid infection and
injury sites on noninvaded cells to produce
antiviral proteins, which prevent viruses
from entering the cell.
- In addition, interferons have been found to
inhibit tumor growth and replication, to
stimulate cytotoxic T cell activity, and to
enhance the inflammatory response. Of
interest, interferon gamma-1b also acts like
an interleukin, stimulating phagocytes to be
more aggressive.
Gender Considerations
Immune Modulators and Pregnancy
Generally, immune modulators are contraindicated
for use during pregnancy and lactation, largely
because these drugs have been associated with fetal
abnormalities, increased maternal and fetal
infections, and suppressed immune responses in
nursing babies.
- Female patients should be informed of the
risk of using these drugs during pregnancy
and receive counseling in the use of barrier
contraceptives.
- If a patient taking immune modulators
becomes pregnant or decides that she wants
to become pregnant, she should discuss this
with her health care 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 lactation.
Because long-term studies of most of these
drugs are not yet available, it may be
prudent to advise patients taking these drugs
to avoid pregnancy if possible.
Immune Stimulants
Are used to energize the immune system when it is
exhausted from fighting prolonged invasion or
when the immune system needs help fighting a
specific pathogen or cancer cell.
- Include the interferons, which are naturally
released from human cells in response to
viral invasion; interleukins, which are
chemicals produced by T cells to
communicate between leukocytes; and the
colony-stimulating factors that are used to
stimulate the bone marrow to produce more
white blood cells in situations where the
levels of these cells are very low and the
patient is at serious risk for infection.
Interferrons
Are substances naturally produced and released by
human cells that have been invaded by viruses.
- They may also be released from cells in
response to other stimuli, such as cytotoxic
T cell activity. A number of interferons are
available for use.
- Several are produced by recombinant DNA
technology, including interferon alfa-2b
(Intron-A), peginterferon alfa-2a (Pegasys),
peginterferon alfa-2b (Peg-Intron), and
interferon beta-1b (Betaseron). Interferon
alfa-n3 (Alferon N) is produced by
harvesting human leukocytes.
- Interferon beta-1a (Avonex) is produced
from Chinese hamster ovary cells. Interferon
gamma-1b (Actimmune) is produced by
Escherichia coli bacteria. The interferon of
choice depends on the condition being
treated.
Therapeutic Actions and Indications
Interferons act to prevent virus particles from
replicating inside cells.
- They also stimulate interferon receptor sites
on noninvaded cells to produce antiviral
proteins, which prevent viruses from
entering the cell.
- In addition, interferons have been found to
inhibit tumor growth and replication, to
stimulate cytotoxic T cell activity and to
enhance the inflammatory response. Of
interest, interferon gamma-1b also acts like
an interleukin, stimulating phagocytes to be
more aggressive.
Pharmacokinetics
The interferons are generally well absorbed after
subcutaneous 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 components to prevent hypersensitivity
reactions.
- 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
childbearing age.
- It is not known whether these drugs cross
into breast milk, but because of the potential
adverse ef ects on the baby, it is advised that
the drugs not be used during lactation 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.
Adverse Effects
Are associated with the use of interferons are
related to the immune or inflammatory reaction that
is being stimulated (stimulating the immune and
inflammatory response causes a flu-like syndrome
with lethargy, myalgia, arthralgia, anorexia,
nausea).
- Other commonly seen adverse effects
include headache, dizziness, bone marrow
depression, depression and suicidal ideation,
photosensitivity, and liver impairment.
 Clinical Important Drug-Drug Interactions
- There are no reported clinically important
drug–drug interactions with the interferons.
Interleukins
Are synthetic compounds much like the interferons;
they communicate between lymphocytes, which
stimulate cellular immunity and inhibit tumor
growth.
- Interleukin-2 stimulates cellular immunity
by increasing the activity of natural killer
cells, platelets, and cytokines. Two
interleukin preparations are available for
use.
- Aldesleukin (Proleukin) is a human
interleukin produced by recombinant DNA
technology using Escherichia coli bacteria.
Oprelvekin (Neumega) is a newer agent that
is also produced by DNA technology.
Therapeutic Actions and Indications
Natural interleukin-2 is produced by various
lymphocytes to activate cellular immunity and
inhibit tumor growth by increasing lymphocyte
numbers and their activity. When interleukins are
administered, there are increases in the numbers of
natural killer cells and lymphocytes, in cytokine
activity, and in the number of circulating platelets.
Pharmacokinetics
The interleukins are rapidly distributed after
injection.
- Aldesleukin, given IV, reaches peak levels
in 13 minutes and has a half-life of 85
minutes.
- Oprelvekin, which is given subcutaneously,
reaches peak levels in 3 to 5 hours and has a
half-life of 7 to 8 hours.
They are primarily cleared from the body by the
kidneys.
Contraindications and Cautions
Interleukins are contraindicated in the presence of
any allergy to an interleukin or Escherichia coli–
produced product to prevent hypersensitivity
reactions. Because they were shown to be
embryocidal and teratogenic in animal studies, they
should not be used during pregnancy.
- Use of barrier contraceptives is
recommended for women of childbearing
age who require one of these drugs. It is not
clear whether the drugs cross into breast
milk, but it is recommended that they not be
used during lactation; if they must be used,
another method of feeding the baby must be
chosen because of the potential for adverse
ef ects in the baby.
- Caution should be used with renal, liver, or
cardiovascular impairment because of the
adverse ef ects of the drugs.
Adverse Effects
The adverse effects associated with the interleukins
can be attributed to their effect on the body during
inflammation (flu-like effects: lethargy, myalgia,
arthralgia, fatigue, fever).
- Respiratory difficulties, CNS changes, and
cardiac arrhythmias also have been reported,
and the patient should be monitored for
these effects and the drug stopped if they do
occur.
- Oprelvekin has been associated with severe
hypersensitivity reactions, and patients
should be closely watched when beginning
therapy and encouraged to report any
difficulty breathing or swallowing, chest
tightness, or swelling.
Clinical Important Drug-Drug Interactions
- There are no reported drug–drug interactions
with the interleukins.
Colony-Stimulating Factors
The colony-stimulating factors are produced by
recombinant DNA technology.
- Filgrastim (Neupogen), pegfilgrastim
(Neulasta), and tbo-filgrastim increase the
production of neutrophils in the bone
marrow with little effect on other
hematopoietic cells.
- Sargramostim (Leukine) increases the
proliferation and differentiation of
hematopoietic progenitor cells and can
activate mature granulocytes and monocytes.
The colonystimulating factor of choice will depend
on the condition being treated.
Therapeutic Actions and Indications
By increasing the production of white cells, the
colony-stimulating factors can be used to reduce the
incidence of infection in patients with bone marrow
suppression, to decrease the neutropenia associated
with bone marrow transplants and chemotherapy,
and to help in the treatment of various blood-related
cancers.
Pharmacokinetics
- Filgrastim can be given IV or by
subcutaneous injection, reaching peak levels
 in 2 hours IV or 8 hours subcutaneously; it
has a half-life of about 220 minutes and a
duration of 4 days; its metabolism and
excretion are not known.
- Pegfilgrastim is only given by subcutaneous
injection with similar onset but has a much
longer half-life, 15 to 80 hours, than
filgrastim.
- Tbo-filgrastim is only given subcutaneously,
reaches peak levels in 4 to 6 hours and has a
half-life of 3.5 hours.
- Sargramostim can be given IV or
subcutaneously with a duration of 6 hours
(IV) or 12 hours subcutaneously. It has a
half-life of 1 to 3 hours; its metabolism and
excretion are not known.
Contraindications and Cautions
Interleukins are contraindicated in the presence of
any allergy to any component of the drug or to
Escherichia coli–produced products to prevent
hypersensitivity reactions.
- Sargramostim is contraindicated in neonates
because of benzyl alcohol in the solution and
with excessive leukemic myeloid blasts in
the bone marrow or peripheral blood, which
could be worsened by the drug.
- These drugs should be used with caution in
pregnancy and lactation because the
potential effects on the fetus or neonate are
not known.
- Sargramostim should also be used with
caution in hepatic or renal failure which
could alter the pharmacokinetics of the drug,
during or immediately after radiation or
chemotherapy because of a potential loss of
effectiveness.
Adverse Effects
The adverse effects associated with colony-
stimulating factors are gastrointestinal (GI) effects
(nausea, vomiting, diarrhea, constipation, anorexia),
headache, fatigue, generalized weakness, alopecia
and dermatitis, and generalized pain and bone pain.
The effects are thought to be associated with the
drug effects on the bone marrow cells and their
increased activity.
Clinically Important Drug–Drug Interactions
The only reported drug–drug interactions associated
with these drugs is an increase in the
myeloproliferative effects of sargramostim when
combined with lithium or corticosteroids; these
combinations should be used with caution.
KEY POINTS
 Immune stimulants assist the immune
system to fight specific pathogens or cancer
cells; in doing so, they cause flu-like
symptoms (lethargy, muscle and joint aches
and pains, anorexia, nausea).
 Interferons are used to treat various cancers
and warts.
 Interleukins stimulate cellular immunity and
inhibit tumor growth.
Immune Suppressants
Are used to block the normal effects of the immune
system in cases of organ transplantation in
autoimmune disorders and in some cancers.
- Often are used in conjunction with
corticosteroids, which block the
inflammatory reaction and decrease initial
damage to cells.
- They are especially beneficial in cases of
organ transplantation and in the treatment of
autoimmune diseases.
- The immune suppressants include the
immune modulators, T and B cell
suppressors, an interleukin receptor
antagonist, and monoclonal antibodies—
antibodies produced by a single clone of B
cells that react with specific antigens.
- There is a new drug, belatacept (Nulojix),
that was approved for the prevention of
acute transplant rejection in adults with
kidney transplants.
New Immunosuppressive Agent
In 2011 belatacept (Nulojix) was approved for the
prevention of acute transplant rejection in adults
with kidney transplants.
- This immunosuppressive is in a new class of
drugs; it is a T cell costimulation blocker.
- It inhibits T cell proliferation and the
production of interleukins and blocks this
first step in the immunologic reaction.
Immune Modulators
Block the release of various cytokines involved in
the inflammatory response and activation of
lymphocytes, decreasing immune activity.
- The result of blocking these chemicals is
immune suppression.
- The immune modulators are a relatively new
class of drugs and include fingolimod
(Gilenya), lenalidomide (Revlimid), and
thalidomide (Thalomid), an old drug with
 new uses, apremilast (Otezla), dimethyl
fumarate (Tecfidera), pomalidomide
(Pomalyst), and teriflunomide (Aubagio).
Therapeutic Actions and Indications
The immune modulators have a number of effects
on the inflammatory system;
- lenalidomide and thalidomide inhibit the
secretion of proinflammatory cytokines and
increase the secretion of anti-inflammatory
cytokines from monocytes and have varying
effects on cell proliferation.
- Fingolimod inhibits the release of
lymphocytes from lymph nodes into the
peripheral blood so they cannot migrate to
activate immune and inflammatory
reactions.
- Fingolimod is the first oral agent for the
treatment of relapsing forms of multiple
sclerosis.
- Lenalidomide is used in treating multiple
myeloma and myelodysplastic syndromes.
- Thalidomide is also used for treating
multiple myeloma and erythema nodosum
leprosum.
- The newer agent apremilast is used for
adults with psoriatic arthritis.
- Dimethyl fumarate and teriflunomide are
used to treat multiple sclerosis;
pomalidomide is a thalidomide analog that is
used in treating multiple myeloma.
Pharmacokinetics
- Fingolimod is slowly absorbed from the GI
tract, reaching peak levels in 12 to 16 hours.
It is metabolized in the liver and excreted
through the kidneys with a half-life of 6 to 9
days.
- Lenalidomide is absorbed quickly from the
GI tract, reaching peak levels in 30 to 90
minutes. It is excreted unchanged in the
urine with a half-life of 3 hours.
- Thalidomide is very slowly absorbed from
the GI tract, reaching peak levels in 3 to 6
hours. The metabolism of thalidomide is not
known; it is excreted in the urine with a half-
life of 12 to 24 hours.
- Pomalidomide is absorbed from the GI tract,
reaching peak levels in 2 to 3 hours. It is
metabolized in the liver and excreted in the
urine with a half-life of 7.5 to 9.5 hours.
- Apremilast is absorbed from the GI tract
with peak levels reached in 2.5 hours. It is
also metabolized in the liver with excretion
in both urine and feces. Apremilast has a
half life of 6 to 9 hours.
- Dimethyl fumarate is absorbed from the GI
tract with peak levels occurring within 2 to
2.5 hours. It is metabolized by esterases
throughout the body with the main excretion
occurring as CO2 through the lungs. The
half-life of this drug is about an hour.
- Oral teriflunomide reaches peak levels in 1
to 4 hours; it is excreted unchanged in the
bile. Most of the drug is eliminated from the
body within 21 days.
Contraindications and Cautions
All of these drugs are contraindicated during
pregnancy because their effects on cells can cause
serious fetal harm; women of childbearing age
should be advised to use barrier contraceptives
when using this drug, and proof that the patient is
not pregnant needs to be documented in the chart
before beginning therapy and periodically during
therapy.
- Teriflunomide is also contraindicated with
severe hepatic impairment which could
become more severe due to the drug effects.
T and B Cell Suppressors
Several T and B cell immune suppressors are
available for use. Of the numerous agents available,
cyclosporine is the most commonly used immune
suppressant.
- Additional agents include abatacept
(Orencia), alefacept (Amevive), azathioprine
(Imuran), cyclosporine (Sandimmune,
Neoral), glatiramer (Copaxone),
mycophenolate (CellCept), pimecrolimus
(Elidel), sirolimus (Rapamune), and
tacrolimus (Prograf).
Therapeutic Actions and Indications
The exact mechanism of action of the T and B cell
suppressors is not clearly understood. It has been
shown that they block antibody production by B
cells, inhibit suppressor and helper T cells, and
modify the release of interleukins and of T cell
growth factor.
- The T and B cell suppressors are indicated
for the prevention and treatment of specific
transplant rejections.
Pharmacokinetics
- Cyclosporine is well absorbed from the GI
tract, reaching peak levels in 1 to 2 hours. It
is extensively metabolized in the liver by the
cytochrome P450 system and is primarily
excreted in the bile. The half-life of the drug
is about 19 hours for Sandimmune and 8.4
 hours for Neoral. It is available as an oral
solution that can be mixed with milk,
chocolate milk, or orange juice for ease of
administration.
- Abatacept must be given as a 30-minute
infusion every 2 to 4 weeks, depending on
the patient’s response. Peak levels are
reached at the end of the infusion. Abatacept
has a half-life of 12 to 23 days and usually
reaches a steady state by 60 days of
treatment. The drug is cleared from the body
by the kidneys.
- Alefacept is rapidly absorbed and can be
given IM or IV. It reaches peak levels in 4 to
6 hours and has a half-life of 270 hours.
- Azathioprine is rapidly absorbed from the
GI tract, reaching peak levels in 1 to 2 hours.
This drug is catabolized in the liver and red
blood cells.
- Little is known about the pharmacokinetics
of glatiramer. Some of it is immediately
hydrolyzed on injection, some enters the
lymph system, and some may actually reach
the systemic circulation.
- Mycophenolate is readily absorbed and
immediately metabolized to its active
metabolite. Most of the metabolized drug is
then excreted in the urine.
- Sirolimus is rapidly absorbed from the GI
tract, reaching peak levels in 1 hour. It is
extensively metabolized in the liver, partly
by the cytochrome P450 system. The drug is
then excreted primarily in the feces.
- Tacrolimus is rapidly absorbed from the GI
tract, reaching peak levels in 1.5 to 3.5
hours. It is extensively metabolized in the
liver by the cytochrome P450 system and is
excreted in the urine.
Contraindications and Cautions
The use of T and B cell suppressors is
contraindicated in the presence of any known
allergy to the drug or its components to prevent
hypersensitivity reactions and during pregnancy and
lactation because of the potential serious adverse ef
ects on the fetus or neonate.
- Caution should be used with renal or hepatic
impairment, which could interfere with the
metabolism or excretion of the drug, and in
the presence of known neoplasms, which
potentially could spread with immune
system suppression.
Adverse Effects
Patients receiving these drugs are at increased risk
for infection and for the development of neoplasms
due to their blocking effect on the immune system.
- Other potentially dangerous adverse effects
include hepatotoxicity, renal toxicity, renal
dysfunction, and pulmonary edema.
- Patients may experience headache, tremors,
secondary infections such as acne, GI upset,
diarrhea, and hypertension.
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.
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).
Therapeutic Actions and Indications
Anakinra specifically antagonizes human
interleukin-1 receptors, blocking the activity of
interleukin-1. Interleukin-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 rheumatoid arthritis.
- Anakinra is used to reduce the signs and
symptoms of moderately to severely active
rheumatoid arthritis in patients 18 years of
age and older who have not responded to the
traditional antirheumatic drugs.
Pharmacokinetics
The recommended dosage is 100 mg/d by
subcutaneous injection.
- Anakinra is administered by subcutaneous
injection and is absorbed slowly, reaching
peak effects in 3 to 7 hours. It is metabolized
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 Escherichia coli–produced products or to
anakinra itself to prevent hypersensitivity reactions.
It should be used with caution during pregnancy and
lactation because the drug may cross the placenta
and enter breast milk. It is also used cautiously in
patients with renal impairment,
immunosuppression, or any active infection because
these could be exacerbated by the ef ects of the
drug. There is an increased risk of infection
whenever this drug is used, and the patient needs to
be protected from exposure to infections and
monitored closely after any invasive procedures.
- Immunizations cannot be given while the
patient is on this drug.
Adverse Effects
Headache, sinusitis, nausea, diarrhea, upper
respiratory and other infections, and injection site
reactions are among the most common adverse
effects.
Clinically Important Drug–Drug Interactions
Patients 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.
Monoclonal 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.
Therapeutic Actions and Indications
Muromonab-CD3, the first monoclonal antibody
approved for use, is a T cell–specific antibody that
was available as an IV agent. It reacted as an
antibody to human T cells, disabling the T cells and
acting as an immune suppressor (see Figure 17.1).
Muromonab was withdrawn from the market in
2014 when other treatments became more readily
available.
- Alemtuzumab is an antibody specific for
lymphocyte receptor sites.
- Basiliximab and daclizumab are specific to
interleukin-2 receptor sites on activated T
lymphocytes; they react with those sites and
block cellular response to allograft
transplants.
- Canakinumab is a specific interleukin-6
blocker and is used for cryopyrin-associated
periodic syndromes and juvenile arthritis.
- 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
tumors that overexpress HER2.
- Blinatumomab, brentuximab, and
obintuzumab are specific T cell antibodies,
altering their function.
- Eculizumab binds to complement proteins
and prevents the formation of the
complement complex.
- Ranibizumab binds to sites of active forms
of vascular endothelial growth factor,
preventing new vascular growth in the area
of injection.
- Ramucirumab and ranibizumab also inhibit
endothelial growth receptors. Ramucirumab
is effective in gastric and lung cancers.
Ranibizumab is used for treating macular
edema and macular degeneration.
- Erlotinib, bevacizumab, pegaptanib, and
tositumomab combined with iodine-131
tositumomab are effective against specific
malignant receptor sites.
- Ibritumomab, ofatumumab, and rituximab
are antibodies specific to sites on activated B
lymphocytes.
- Natalizumab is an antibody specific to
surface receptors on all leukocytes except
neutrophils.
- Nivolumab and pembrolizumab are
antibodies to programmed death receptor-1
sites and are used for treating specific
cancers.
- Omalizumab is an antibody to
immunoglobulin E, an important factor in
allergic reactions. It has not had a great deal
of success because of related respiratory
adverse effects but is now approved for
chronic urticaria conditions.
- Palivizumab is specific to the antigenic site
on respiratory syncytial virus (RSV); it
inactivates that virus. It is used to prevent
RSV disease in high-risk children.
- Tocilizumab, siltuximab, and ustekinumab
are antibodies specific to interleukins.
- Belimumab, which is a specific inhibitor of
B lymphocyte stimulator which inhibits the
survival of B lymphocytes and their
differentiation into immunoglobulin-
producing cells. It is used for adult patients
with active, autoantibody-positive systemic
lupus erythematosus who are receiving
standard therapy.
- Ipilimumab is a human cytotoxic T cell
antigen- 4–blocking antibody. By blocking
this site, T cells are activated and proliferate
at a faster rate. It is used to treat patients
with unresectable or metastatic melanoma. It
is associated with potentially fatal
immunemediated reactions, and its use must
be carefully evaluated.
- Vedolizumab is an integrin blocker that
inhibits the movement of T cells across the
gastric mucosa. It is used for treating
ulcerative colitis and Crohn’s disease in
 patients who do not respond to traditional
therapies.

Pharmacokinetics

With the exception of erlotinib (an oral agent), all of

the monoclonal antibodies have to be injected. They
can be given IV, IM, or subcutaneously. Because
antibodies are proteins, they are rapidly broken
down in the GI tract. They are processed by the
body like naturally occurring antibodies.

Contraindications and Cautions

Monoclonal antibodies are contraindicated in the

presence of any known allergy to the drug or to
murine products to prevent hypersensitivity
reactions and in the presence of fluid overload,
which could be exacerbated. They should be used
cautiously with fever (treat the fever before
beginning therapy) and in patients who have had
previous administration of the monoclonal antibody
(serious hypersensitivity reactions can occur with
repeat administration). Because of the potential for
adverse effects, they should not be used during
pregnancy or lactation unless the benefit clearly
outweighs the potential risk to the fetus or neonate. FIGURE 17.2 Variety of adverse effects and
toxicities associated with immune modulators.
Adverse Effects

The most serious adverse effects associated with the
use of monoclonal antibodies are acute pulmonary
edema (dyspnea, chest pain, wheezing), which is
associated with severe fluid retention, and cytokine
release syndrome (flu-like symptoms that can
progress to thirdspacing of fluids and shock). Other
adverse effects that can be anticipated include fever,
chills, malaise, myalgia, nausea, diarrhea, vomiting,
and increased susceptibility to infection and cancer
development.
Clinically Important Drug–Drug Interactions
Use caution and arrange to reduce the dose if a
monoclonal antibody is combined with any other
immunosuppressant drug because severe immune
suppression with increased infections and
neoplasms can occur.
- Eculizumab can lead to intravascular
hemolysis with resultant fatigue, pain, dark
urine, shortness of breath, and blood clots.
- Bevacizumab is associated with GI
perforation, hemorrhage, and impaired
healing.
- Erlotinib is reserved for patients whose
disease has progressed after other therapies.
The manufacturer of natalizumab stopped
marketing the drug weeks after its release
because of reports of CNS complications. It
was returned to the market in June 2006
with warnings about the potential for CNS
complications.
- Blinatumomab is associated with potentially
life-threatening cytokine release syndrome
and life-threatening neurological toxicities.
- Brentuximab and obinutuzumab are
associated with progressive multifocal
leukoencephalopathy.
- Ramucirumab is associated with potentially
life-threatening hemorrhage.
- Belimumab is associated with CNS effects
including an increased risk for depression
and suicidality. There is also a risk of
hypersensitivity reactions during the IV
infusion, and patients should be
premedicated before each infusion.
- Ipilimumab has been associated with severe
to fatal immune-mediated reactions due to
the activation and proliferation of T cells. It
 has a black box warning about the
possibility and suggests baseline thyroid and
liver function tests and exams of the skin,
neurological function, and GI function.

KEY POINTS

 Immune suppressants are used to depress the

immune system when needed to prevent
transplant rejection or severe tissue damage
associated with autoimmune disease.
Research is ongoing to extend the use of
various immune suppressants to other
situations, including various autoimmune
disorders.
 Increased susceptibility to infection and
increased risk of neoplasm are potentially
dangerous effects associated with the use of
immune suppressants. Patients need to be
protected from infection, injury, and
invasive procedures.

SUMMARY OF CHAPTER 17

 Immune stimulants boost the immune

system when it is exhausted from fighting
off prolonged invasion or needs help to fight
a specific pathogen or cancer cell. They
include interferons and interleukins.
 Interferons are naturally released from cells
in response to viral invasion; they are used
to treat various cancers and warts.
 Interleukins stimulate cellular immunity and
inhibit tumor growth; they are used to treat
very specific cancers.
 Adverse effects seen with immune
stimulants are related to the immune
response (flu-like symptoms, including
fever, myalgia, lethargy, arthralgia, and
fatigue).
 Immune suppressants are used to depress the
immune system when needed to prevent
transplant rejection or severe tissue damage
associated with autoimmune disease.
Research is ongoing to extend the use of
various immune suppressants to other
situations, including various autoimmune
disorders.
 Increased susceptibility to infection and
increased risk of neoplasm are potentially
dangerous effects associated with the use of
immune suppressants. Patients need to be
protected from infection, injury, and
invasive procedures.