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Abstract
Immune-mediated disease is a common diagnostic and therapeutic challenge in veterinary medicine. These diseases
can be primary, with no identified trigger, or secondary, caused by the recent administration of medications or an
underlying disease process. As immune-mediated diseases are increasingly recognized and diagnosed, veterinary
practitioners need to understand and be comfortable with the use of immunosuppressive agents. This article reviews
immunosuppressants currently used in veterinary medicine; their efficacy, recommended doses, and adverse effects;
and how to choose an adjunctive immunosuppressant for immune-mediated disease.

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CONTINUING EDUCATION

INTERNAL MEDICINE

Immunosuppressant Therapy:
What, When, and Why
Stuart Walton, BVSc, BScAgr, MANZCVS (SAIM), DACVIM
Alexis Hoelmer, DVM
University of Florida College of Veterinary Medicine, Gainesville, Florida

An immunosuppressant is any agent that long-term medications intended to manage the

decreases the body’s immune response. These immune response). Initially, these drugs are
drugs typically target a specific point of either commenced at a known immunosuppressive
the humoral or the cell-mediated immune dose, with the eventual goal being to taper them
response and can be used to treat primary or to the lowest effective dose.
secondary immune-mediated disease. In primary
disease, immunosuppressants are used to Immunosuppressant drugs are categorized into
manipulate the body’s own immune response. steroid medications (e.g., prednisone,
When a secondary cause of immune-mediated prednisolone, dexamethasone, budesonide),
disease is identified, initial treatment should be calcineurin inhibitors (e.g., cyclosporine),
aimed at discontinuing the inciting agent or antiproliferative medications (e.g., azathioprine,
treating the underlying disease process. mycophenolate, leflunomide), and mechanistic
target of rapamycin inhibitors (not currently
Currently, a variety of immunosuppressants are used routinely in veterinary medicine). This
used in veterinary medicine. The most article focuses on the first 3 categories and
commonly used drugs are considered includes some novel adjunctive therapies that are
“maintenance” drugs in human medicine (i.e., currently used in veterinary medicine.

Take-Home Points

ƒ Immune-mediated disease available for severe or refractory time. Tapering should only be
is a common diagnostic and cases. attempted after clinical remission
therapeutic challenge in dogs and has been achieved.
cats. ƒ Drug selection should be based
on anticipated side effects, owner ƒ Vaccination should be carefully
ƒ Glucocorticoids are considered finances, dosing schedule, and considered in dogs and cats
the mainstay of therapy for time to expected response. treated with immunosuppressive
most immune-mediated medications. Vaccine titers may
diseases, but numerous other ƒ Immunosuppressive medications be a reasonable alternative to
immunosuppressive drugs are should be tapered slowly, 1 at a routine vaccination.

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INDICATIONS FOR FIRST-LINE IMMUNOSUPPRESSANT

IMMUNOSUPPRESSANT THERAPY DRUGS
Immunosuppressants are used to treat primary disease.
Immune-mediated disease, considered to be a disease of Glucocorticoids
exclusion, generally involves ruling out as many Glucocorticoids are the mainstay of therapy due to
secondary underlying causes as diagnostic abilities their availability, cost, efficacy, and rapid onset of
allow. Common disease processes thought to be driven action. Steroids are initially started at an
by an inappropriate immune response include immune- immunosuppressive dose until clinical remission is
mediated thrombocytopenia (ITP); immune-mediated achieved, then slowly tapered to the lowest effective
anemias (e.g., immune-mediated hemolytic anemia dose over weeks to months (TABLE 1). Clinical
[IMHA], precursor-targeted immune-mediated anemia, improvement is often noted within 48 hours, with a
pure red cell aplasia); steroid/immunosuppressant- steady state typically achieved by day 4.1 However,
responsive enteropathy; immune-mediated polyarthritis clinical improvement can take up to 2 weeks.1
(IMPA); atopic dermatitis; and meningoencephalitis of
unknown etiology (MUE), including granulomatous Prednisone and prednisolone are the most used
meningoencephalitis, necrotizing meningoencephalitis, steroids in veterinary medicine. Prednisone, a prodrug,
necrotizing leukoencephalitis, and steroid-responsive requires hepatic metabolism to its active form
meningitis–arteritis. prednisolone.2 Prednisolone is preferable in cats
because they lack the ability to convert prednisone into
Other diseases encountered less frequently include prednisolone.2
perianal fistulas, myasthenia gravis (MG), immune-
mediated chronic hepatitis, immune-mediated Dexamethasone can be used in animals unable to take
polymyositis, and immune-mediated or adequately absorb oral steroids (e.g., hospitalized
glomerulonephritis. Immunosuppressive therapy often animals, animals with severe protein-losing
addresses neoplastic disease as well, the treatment of enteropathies [PLEs]). When patients are reliably
which can have significant overlap with many eating or their disease has stabilized, oral steroids are
idiopathic immune-mediated diseases. However, initiated and dexamethasone can be discontinued.
treatment of neoplastic disease and in-depth use of Dexamethasone is formulated as either pure
chemotherapeutics are beyond the scope of this article. dexamethasone or dexamethasone sodium phosphate.

TABLE 1 Glucocorticoids for First-Line Immunosuppressive Therapy

POTENCY
RELATIVE TO
PREDNISONE/
PREDNISOLONE DURATION OF IMMUNOSUPPRESSIVE
DRUG POWER EFFECT USES ACTION DOSE

Maintenance 2 mg/kg PO q24h or

Prednisone/ of dogs with 50 mg/m2 PO q24h (dogs
1 Systemic 12–36 hours
prednisolone immune- >25 kg), not to exceed
mediated disease 60 mg PO total per day

In-hospital,
severe 0.25–0.3 mg/kg q24h IV,
Dexamethasone 7–10 Systemic 32–48 hours
protein-losing IM, or SC
enteropathy

Variable across 3 mg/m2 PO q24h

dose and with or
Diabetic cats, individual Cat: 0.5–0.75 mg/cat PO
Intestinal tract,
Budesonide 15 dogs/cats with patients, 10.1–15.1 Dog: ≤7 kg: 1 mg PO q24h
liver
cardiac disease hours (based 7.1–15 kg: 2 mg PO q24h
on human 15.1–30 kg: 3 mg PO q24h
literature) >30 kg: 5 mg PO q24h

Dog: 1 mg/kg (or

Fractious cats
20–40 mg/dog)
Methylprednisolone that require a
1.25 Systemic ~21 days IM every 1–3 weeks
acetate longer-acting
Cat: 10–20 mg/cat IM
injectable agent
every 1–3 weeks

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Dexamethasone sodium phosphate is highly water severely affected patients or in patients that are
soluble and has a rapid onset of action when refractory to a first-line agent.
administered intravenously.1 Clinicians should note
that dexamethasone sodium phosphate is labeled at a
concentration of 4 mg/mL but only contains 3 mg/mL Cyclosporine
of dexamethasone. Dexamethasone may also be Cyclosporine, a calcineurin inhibitor, is one of the most
preferred in patients with cardiovascular disease when common secondary agents used in veterinary
fluid retention is undesirable, due to minimal medicine.11,13 Two commercial formulations (modified
mineralocorticoid activity.3 and nonmodified) exist. Nonmodified formulations
(e.g., Sandimmune [Novartis, novartis.com]) have
Budesonide, a locally active glucocorticoid, has weak significant variability in absorption and
mineralocorticoid activity.4 It is available as an enteric- pharmacokinetics among individuals.13 Newer,
coated tablet and can be used in patients with chronic modified forms (e.g., Neoral [Novartis], Atopica
enteropathies that cannot tolerate systemic [Elanco, elanco.us]) are ultramicronized preparations
glucocorticoid therapy, most commonly diabetic cats.5 that are more readily and predictably absorbed.13 Only
There is conflicting information on whether modified forms should be used in veterinary patients.
budesonide is efficacious in dogs with chronic Modified form bioavailability in dogs is approximately
enteropathies.4,6,7 Although budesonide has less 35% compared with 20% to 25% for the nonmodified
systemic action than prednisolone, it still suppresses the form.13 Atopica, the only veterinary formulation
hypothalamic-pituitary-adrenal axis and should be used approved by the U.S. Food and Drug Adminstration, is
cautiously when steroids are relatively contraindicated.8 preferred based on extensive testing in veterinary
patients. Generic modified forms of cyclosporine may
Methylprednisolone acetate (e.g., Depo-Medrol; have decreased efficacy but can be considered when
Pfizer, pfizer.com), is a long-acting injectable steroid. Atopica is cost prohibitive.11 Alternatively, cyclosporine
Clinicians should use caution when prescribing this can be combined with ketoconazole to reduce the
medication due to its diabetogenic and plasma volume– immunosuppressive dose of cyclosporine.14,15 It is
expanding effects.9 While this drug may be beneficial important to note that clinical efficacy may not be seen
when immunosuppressive therapy is warranted and for up to 3 to 4 weeks, and a steady state may not be
daily medication administration is not possible, such as achieved in some patients.11
in fractious cats, its long-acting nature increases risk of
significant side effects. A single intramuscular or In animals without immediately life-threatening disease
subcutaneous dose can last for several weeks and may and/or that cannot tolerate steroid therapy, modified
induce congestive heart failure in animals with cyclosporine has demonstrated efficacy as a sole agent
underlying cardiovascular disease or clinical diabetes for perianal fistulas.14-16 Although improvement of
mellitus in predisposed animals.9 Because of this, lesions is expected after 4 weeks, tapering should only
methylprednisolone acetate should not be considered be attempted after lesions have completely resolved (12
routinely in animals requiring glucocorticoid therapy. to 16 weeks on average).14-16 Cyclosporine has also been
used with good success in cases of atopic dermatitis and
inflammatory colorectal polyps, along with several
Alternative Drugs other immune-mediated conditions.11,13,17 Efficacy in
Drugs generally considered as second-line therapy are, these conditions is similar to that of glucocorticoids;
in certain disease processes, efficacious as a first-line however, cyclosporine is generally preferred due to
agent (TABLE 2). Even in these cases, steroid therapy is fewer side effects.13,18 Steroids are commonly initiated
initiated concurrently due to the delayed onset of concurrently to achieve a rapid clinical response.
action of other immunosuppressant drugs. However,
patients commonly fail to respond to glucocorticoids or
other first-line agents, leading to the need to use Mycophenolate
adjunctive, or second-line, agents. Few studies Mycophenolate, or mycophenolic acid, inhibits purine
evaluating these drugs exist, with most clinicians synthesis. It decreases proliferation of T and B cells.2
choosing adjunctive immunosuppressants based on Mycophenolic acid undergoes enterohepatic
previous experience or anecdotal evidence. The recirculation; therefore, 2 plasma peaks are observed,
addition of a secondary agent should be considered in the first at 1 to 2 hours following oral administration

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TABLE 2 Secondary Agents: Pharmacodynamics, Pharmacokinetics, Indications, and Dosing

PRIMARY
MECHANISM METABOLISM/
DRUG OF ACTION EXCRETION STARTING DOSE FIRST-LINE THERAPYa

ƒ Atopic dermatitis
ƒ IMHA
ƒ Nuclear factor-κB
2 mg/kg PO q24h or ƒ IMPA
inhibitor
Prednisone/ 50 mg/m2 PO (dogs ƒ Immune-mediated polymyositis
ƒ Cytokine inhibition Liver/urine
prednisolone >25 kg), not to exceed 60 ƒ ITP
ƒ Lymphocyte
mg total per day ƒ MUE
apoptosis
ƒ SRE
ƒ SRMA

ƒ Atopic dermatitis (5 mg/kg PO

5 mg/kg PO q12h q24h)
Liver or 1–2 mg/kg PO ƒ Chronic hepatitis10
ƒ Calcineurin
Cyclosporine (cytochrome q12h combined with ƒ IMPA
inhibitor
P450)/bile ketoconazole 8–10 mg/kg ƒ Inflammatory colorectal polyps
PO q24h ƒ Perianal fistula (4–8 mg/kg PO
q12h)

ƒ Purine synthesis ƒ Immune-mediated glomerular

Mycophenolate Liver/urine 10 mg/kg q12h (IV or PO)
inhibitor disease

2 mg/kg PO q24h for

ƒ No evidence to support first-line
Azathioprine ƒ Purine antagonist Liver/urine 2–4 weeks, then 1–2 mg/
therapy
kg PO q48h

ƒ Pyrimidine Gastrointestinal,
Leflunomide 2 mg/kg PO q24h ƒ IMPA (3–4 mg/kg PO q24h)
synthesis inhibitor liver/urine, bile

IMHA = immune-mediated hemolytic anemia; IMPA = immune-mediated polyarthritis; ITP = immune-mediated thrombocytopenia;
MG = myasthenia gravis; MUE = meningoencephalitis of unknown etiology; SA = sebaceous adenitis; SRE = steroid/immunosuppressant-responsive
enteropathy; SRMA = steroid-responsive meningitis–arteritis.
a
Doses only specified when recommendation differs from standard starting dose
b
Most evidence to support use and authors’ recommendations for adjunctive therapy

and the second 6 to 12 hours later.19 The half-life in also has demonstrated efficacy in immune-mediated
dogs is approximately 8 hours.19 Although dosing every skin disease (e.g., pemphigus foliaceus, vesicular
8 hours would be ideal in order to optimize cutaneous lupus erythematosus, epidermolysis bullosa)
immunosuppression, this is not recommended due to when combined with glucocorticoid therapy.22
unacceptable gastrointestinal toxicity.19,20

One benefit of mycophenolate over other secondary Azathioprine

agents is the availability of an intravenous form. At the Azathioprine, a prodrug of mercaptopurine,
authors’ institution, intravenous mycophenolate has antagonizes purine metabolism. This results in
been used adjunctively with injectable dexamethasone inhibition of lymphocyte proliferation and DNA and
in unstable IMHA patients when therapeutic plasma RNA production.2 There is evidence that lymphocyte
exchange is cost prohibitive. response is decreased within 7 days of therapy.23
However, a steady state is not achieved for 2 to
Based on anecdotal evidence, mycophenolate is 3 weeks, and clinical response may not be observed for
considered a first-line therapy for immune-mediated up to 5 weeks due to greater effect on delayed
glomerulonephritis, the diagnosis of which should hypersensitivity and cellular immunity than on
ideally be supported by renal biopsy.21 Mycophenolate humoral antibody responses.23

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A loading dose is recommended in humans, but this

recommendation does not translate to dogs and
TIME TO
SECOND-LINE THERAPYa STEADY STATE
cats.18,28,29 Studies on the use of leflunomide in animals
are relatively limited. However, there is some evidence
for leflunomide as a first-line agent for IMPA, and as a
second- or third-line agent in refractory cases of
4–5 days inflammatory colorectal polyps.18,30,31 Patients should
be treated at an initial immunosuppressive dose for at
least 6 weeks before tapering is attempted.18,30

ƒ Chronic hepatitisb
ƒ IMHAb
ƒ IMPAb 2–4 weeks SECOND-LINE AGENTS IN
ƒ ITPb (may not be IMMUNE-MEDIATED DISEASE
ƒ MG achieved in
ƒ MUE (5–10 mg/kg PO q12h)b some patients)11 In cases of immune-mediated anemia and ITP, the
ƒ SA (5 mg/kg PO q24h) addition of a second-line agent should be considered if
ƒ SREb
glucocorticoids alone are insufficient or if significant
ƒ Chronic hepatitis adverse effects are expected (TABLE 3). It is especially
ƒ IMHAb
ƒ IMPA recommended in patients that have life-threatening
ƒ Immune-mediated skin diseaseb
1–3 weeks
illness at presentation and in patients that are
ƒ ITPb
ƒ MG
transfusion dependent after 7 days of treatment.27
ƒ MUE (10–20 mg/kg PO q12h)b Insufficient evidence exists as to the superiority of any
ƒ SRE single secondary agent over another for these diseases.
ƒ IMHA
ƒ IMPA
ƒ Immune-mediated polymyositis12
The authors preferentially use either cyclosporine or
2 weeks
ƒ ITP mycophenolate for both immune-mediated anemia and
ƒ MG ITP. The choice between the 2 agents is generally based
ƒ MUE
on the size of the patient, as cyclosporine can be cost
ƒ IMHA
ƒ IMPAb
prohibitive in larger dogs, along with the ability of the
1–3 weeks patient to take oral medications.
ƒ Inflammatory colorectal polyps
ƒ ITP

Second-line use of cyclosporine, mycophenolate,

azathioprine, or leflunomide can also be considered in
severe or refractory cases of MUE, MG, steroid-
responsive enteropathy, and chronic hepatitis. Again,
evidence is lacking for superiority of any second-line
There is less evidence for use of azathioprine as a agent over another.
secondary agent than for cyclosporine or
mycophenolate. It has been used successfully with At the authors’ institution, cyclosporine and
IMHA, ITP, MG, immune-mediated polymyositis, and mycophenolate are generally used as tertiary agents
MUE.21,24-26 A potential benefit of azathioprine is that (after steroids and cytarabine) in severe or refractory
after 2 to 3 weeks, the dosing interval may be decreased cases of MUE.
to every other day until treatment is discontinued,
which may confer a significant financial advantage The authors preferentially use cyclosporine as
compared with other secondary agents.27 adjunctive therapy to glucocorticoids in cases of
chronic hepatitis and inflammatory bowel disease.

Leflunomide
Leflunomide, a pyrimidine synthesis inhibitor, inhibits ALTERNATIVE
autoimmune T-cell proliferation and autoantibody IMMUNOMODULATORY AGENTS
production by B cells. It acts almost exclusively via its Options outside of traditional immunosuppressants
primary active metabolite, teriflunomide.28,29 that have been demonstrated to be efficacious in
specific disease processes include:

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1. Vincristine for ITP. Vincristine increases circulating Clinician considerations when choosing a second
platelet numbers by day 5 postadministration.32 These immunosuppressant therefore include:
platelets are thought to function similarly to mature ■ Patient comorbidities
platelets.33 The drug is often administered as a single ■ Other medications the patient is receiving and
intravenous injection at 0.02 mg/kg. This dose should potential interaction with the drugs being considered
be used cautiously in dogs that exceed 25 kg and ■ Existing evidence for the use of specific agents in the
should be compared to a mg/m2 dose. The total dose disease being treated
should never exceed 0.5 mg/m2. Although vincristine ■ Monitoring requirements
shortens hospitalization time, it is not associated with ■ Availability of appropriate formulation/tablet size for
increased survival or remission rates.32,33 patient
2. Human intravenous immunoglobulin (IVIG). At a ■ Onset of action
dose of 0.5 g/kg, administered as a constant-rate ■ Adverse effects
infusion over 6 to 12 hours, IVIG has shown results ■ Frequency of dosing and realistic owner commitment
similar to those of vincristine in ITP patients, but it is ■ Financial commitment
not readily available for use in many veterinary
hospitals and is much more expensive than Drug choice should ultimately be based on anticipated
vincristine.34 side effects, financial commitment, dosing schedule,
3. Cytarabine. Cytarabine is routinely used as an and time to expected response. When choosing a
adjunctive initial treatment for MUE. Two protocols secondary or tertiary agent, it is important to avoid
exist: drugs that have similar mechanisms of action. At
A. Subcutaneous: 50 mg/m2 q12h for initiation of immunosuppressive therapy, clinicians
2 consecutive days or q2h for 4 doses.35,36 should have a plan in place for monitoring and dose
B. Constant-rate infusion: 100 to 200 mg/m2 over adjustment, as well as a contingency plan if the animal
8 to 24 hours.35,36 does not respond appropriately.
If necessary based on clinical signs, both protocols can
be followed with subcutaneous injections 3 weeks later
at a dose of 50 mg/m2 q12h for 2 consecutive days. MONITORING AND
This protocol can be repeated every 3 weeks for 3 to DOSAGE CHANGES
4 cycles.35,37 Prior to initiating immunosuppressant therapy, a
3. Chlorambucil. Chlorambucil should be considered as comprehensive assessment (i.e., complete blood count,
an adjunctive therapy in refractory cases of PLEs. serum biochemical profile, urinalysis) of the patient
Initial doses of 4.4 mg/m2 PO q24h have resulted in should be performed. These values should be
significant improvement in serum albumin monitored periodically, with timing based on the
concentration after 2 weeks.38 Alternatively, dosing specific drug (TABLE 3). Due to an increased risk of
may be spread out and administered at 20 mg/m2 infection, urinalysis and urine culture should be
every 2 weeks in cats and dogs.2 Chlorambucil, in performed if lower urinary tract signs (e.g., pollakiuria,
combination with prednisolone, has been associated stranguria, hematuria) develop. A complete blood
with increased survival time compared to treatment count should be performed if patients become
with prednisolone and azathioprine.38 systemically unwell (e.g., fever, lethargy, decreased
appetite). In patients that develop nonhealing wounds,
fungal and bacterial culture and susceptibility testing is
CHOOSING THE RIGHT recommended due to the increased risk of
IMMUNOSUPPRESSANT opportunistic infection.39 Additionally, if a systemically
Although glucocorticoids are often the first-line therapy ill patient develops a new heart murmur, an
for immune-mediated disease, potential profound side echocardiogram should be performed to look for
effects, especially in larger dogs, and conditions in evidence of endocarditis.
which glucocorticoid therapy is considered suboptimal
(e.g., diabetes mellitus, cardiovascular disease, renal Drug tapering can be attempted in patients that are
disease) often warrant a second immunosuppressant in clinically stable or in remission for at least 2 weeks.27
patients needing long-term therapy. Although Tapering should be no more than 25% every 2 to
numerous agents exist, there is little evidence to support 4 weeks.27 Clinicians and owners should monitor these
their routine use for or superiority in specific diseases. patients for signs of relapse. If signs of relapse are

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noted, the dose should be increased back to either the Currently, the only laboratory offering TDM for
initial induction dose (if fulminant disease is present) cyclosporine is Auburn University’s Clinical
or the last dose the patient was receiving before the Pharmacology Laboratory. Pharmacodynamic testing
most recent dose reduction (in cases of mild disease).27 was previously offered at Mississippi State University
In patients receiving multiple immunosuppressants, the but is no longer available.
first agent should be tapered completely before
attempting to taper the second agent. Glucocorticoids Submission of whole blood is recommended as 50% of
are initially tapered due to adverse effects associated the drug in blood is located in red blood cells. Studies
with long-term use. are lacking to support whether peak (2 hours after drug
administration) or trough concentrations better
Therapeutic drug monitoring (TDM) may be represent clinical response (except for in cases of
considered in patients that are refractory to the drug or inflammatory bowel disease and perianal fistulas, as
experience unexpected side effects. TDM is most previously mentioned). The more aggressive approach
effective in diseases for which a therapeutic level exists is to target trough concentrations; however, peak
that correlates with clinical response. concentrations may be sufficient.11 Use of cyclosporine
and TDM should be considered carefully in dogs with
the MDR1 (multidrug resistance 1) gene mutation due
Cyclosporine to possible increased sensitivity.11,16
Cyclosporine monitoring is performed to avoid
toxicosis and establish an individual’s therapeutic range.
Trough therapeutic range concentrations (i.e., blood Leflunomide
sampling just prior to the next dose) have been Trough concentrations can be measured 1 to 2 weeks
established for inflammatory bowel disease and perianal after starting therapy or adjusting dose.40 In some cases,
fistulas at 100 to 600 ng/mL (the higher for induction, the half-life may be short enough to necessitate
the lower for maintenance). These ranges have been measurement of peak and trough concentrations. The
associated with positive clinical response.11,17 therapeutic range is 20 to 30 µg/mL.29 TDM can be

TABLE 3 Secondary Agents: Monitoring, Adverse Effects, and Cost

MONITORING THERAPEUTIC DRUG
DRUG ADVERSE EFFECTS RELATIVE COSTb
PARAMETERSa MONITORING

CBC and serum biochemical

Polyuria/polydipsia,
profile 2 weeks after
Prednisone/ polyphagia, thinning of
initiation of therapy, None $
prednisolone skin, muscle loss, excessive
then every 2–3 months
panting
throughout therapy

Serum biochemical Vomiting, diarrhea, gingival

Drug level performed
Cyclosporine profile every 2–3 months hyperplasia, opportunistic $$$
at Auburn University
throughout therapy fungal infections

CBC every 2 weeks for

IV: $$
the first month of therapy, Not performed in
Mycophenolate Diarrhea, myelosuppression (single 500 mg vial)
then every 2–3 months veterinary patients
PO: $
throughout therapy

CBC and serum biochemical

profile every 2 weeks for the Hepatotoxicity,
Not performed in
Azathioprine first 2 months of therapy, myelosuppression, $
veterinary patients
then every 1–2 months gastrointestinal effects
throughout therapy

CBC and serum biochemical Dose dependent:

profile every 2 weeks for the gastrointestinal effects,
Drug level performed
Leflunomide first 2 months of therapy, idiopathic hemorrhage, $
at Auburn University
then every 1–2 months myelosuppression, cough,
throughout therapy hepatotoxicity
CBC = complete blood count
$ = <$50; $$ = $51–$100; $$$ = >$100
a
Monitoring parameters vary depending on disease process. Listed recommendations represent minimum standards in patients receiving long-term
therapy.
b
Based on GoodRx (goodrx.com) cost for 1 month at standard starting dose for a 20-kg dog

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performed at the Auburn University Clinical Cyclosporine

Pharmacology Laboratory. This level may not correlate Vomiting and diarrhea are the most common side
to a positive clinical response but can be used as a effects of cyclosporine. Side effects are self-limiting, last
guide. If no clinical response is noted after the expected several days to several weeks, and are responsive to dose
treatment duration and trough concentrations are reduction.2,11,13 Side effects can be mitigated by freezing
above the therapeutic range, clinicians should consider capsules 30 to 60 minutes prior to administration and
either increasing the drug dose or switching to a dividing the dose throughout the day. Cyclosporine is
different immunosuppressive drug. most effective when given on an empty stomach but
can be given with a small amount of food to try to
mitigate gastrointestinal effects.
ADVERSE EFFECTS
Treatment with any immunosuppressive medication A less common side effect, specifically in dogs, is
increases risk of infection, gastrointestinal upset (e.g., gingival hyperplasia, which is more likely to necessitate
vomiting, diarrhea, anorexia), and myelosuppression. drug discontinuation.2,11,13 Rarely, hirsutism and
Common side effects associated with specific hyperplastic dermatitis have been reported.11 Caution
medications are discussed below and are listed in should be used in patients with diabetes mellitus due to
TABLE 3. Owners should be educated on signs to be the possibility of the drug increasing serum glucose.43
aware of that may necessitate immunosuppressant dose Additionally, cyclosporine therapy has been associated
adjustment or may require symptomatic supportive with the development of opportunistic fungal
care. These include: infections in dogs, reported to be 7 times more likely
1. Decreased appetite, vomiting, or diarrhea. These are than with other immunosuppressive medications.38
self-limiting and do not require medication
discontinuation in most cases. Addition of supportive
medications (e.g., maropitant, mirtazapine) or Mycophenolate
adjustment of how the medication is given (e.g., give Dose-dependent diarrhea is the most common side
with a small amount of food, split dose throughout effect of mycophenolate use.20 The incidence of
the day) may be necessary. diarrhea is higher with oral use than intravenous use
2. Signs that may be suggestive of infection or sepsis, and typically does not occur until after 1 to 2 weeks of
including fever, lethargy, or decreased appetite. therapy.20 Clinicians should start at the lower end of the
3. Evidence of relapse. These signs will be specific to the dosing range (10 mg/kg) and titrate up if the dose is
disease being treated. well tolerated after 2 weeks.20 Absorption is most
effective when given on an empty stomach but can be
It is recommended that dogs and cats receiving given with a small amount of food to try to mitigate
immunosuppressants be kept on monthly flea, tick, and gastrointestinal effects.19 Uncommonly, patients may
heartworm preventives. Immunocompromised patients develop anemia, neutropenia, or thrombocytopenia.20
should not be fed a raw diet due to increased risk of
bacterial translocation leading to systemic infection There is a black box warning for increased risk of
with food-borne pathogens.41,42 lymphoma, pregnancy loss, and congenital
malformations in humans; therefore, owners should use
caution when handling this drug.
Steroids
Side effects commonly seen in animals receiving
short-term steroid therapy are polyuria and Azathioprine
compensatory polydipsia, polyphagia, and excessive Azathioprine has the potential to cause
panting.1,2 Long-term effects include thinning of skin hepatotoxicosis.2,44 This generally occurs within the
and haircoat, muscle atrophy, hypertension, and first several weeks of treatment and can be idiosyncratic
hypercoagulability. Side effects tend to be more or dose-dependent. Marked hepatotoxicity appears to
pronounced in dogs than in cats.2 They are also be an idiosyncratic reaction.27 However, subclinical
pronounced at higher doses; therefore, larger dogs that hepatotoxicity is relatively common (15% of patients in
require higher doses may be more severely affected. For 1 study) and can be dose-dependent, primarily
this reason, it is recommended to use mg/m2 rather manifesting as increases in alanine transaminase and
than mg/kg dosing in large-breed dogs (TABLE 1). alkaline phosphatase levels.44

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Myelosuppression is uncommon in dogs.2,45 Marked unexplained hemorrhage, thrombocytopenia,

myelosuppression appears to be idiosyncratic and may leukopenia, anemia, and hypercholesterolemia.30,47
be reversible if discovered early. As with many other Vomiting and lethargy have been reported in cats.28
immunosuppressants, caution is advised when handling
azathioprine, as there is a black box warning for
increased risk of lymphoma in humans.46 DRUG INTERACTIONS
Before an additional medication is administered to a
Azathioprine is not recommended in cats due to low patient, consultation of a drug formulary is
activity of thiopurine methyltransferase, leading to a recommended to review any possible interactions.
greater incidence of azathioprine toxicity.45 Combining immunosuppressive medications not only
has additive effects on immune system suppression but
also increases the risk for myelosuppression. Numerous
Leflunomide medications have been reported to alter the metabolism
Adverse effects of leflunomide reported in dogs appear or absorption of immunosuppressive agents and
to be dose related and can include gastrointestinal increase the risk of adverse effects. Select drug-specific
disturbances, dyspnea, cough, increased liver enzymes, interactions are listed in TABLE 4.

TABLE 4 Important Drug Interactionsa

DECREASES INCREASED SERUM
METABOLISM/SERUM INCREASED RISK OF CONCENTRATION/RISK
DRUG CONCENTRATION ADVERSE EFFECTS OF TOXICITY

Prednisone/ Azole antifungals ƒ Gastrointestinal ulceration: Macrolide antibiotics (e.g.,

prednisolone (e.g., ketoconazole), nonsteroidal anti-inflammatory azithromycin), tylosin
cholestyramine, mitotane, drugs (e.g., carprofen), other
phenobarbital steroids
ƒ Hypokalemia: amphotericin B,
digoxin, furosemide
ƒ Tendonitis/tendon rupture:
fluoroquinolones
ƒ Steroid use in diabetic patients
increases insulin requirements

Cyclosporine Azathioprine, clindamycin, ƒ Hyperkalemia: potassium Allopurinol, amiodarone,

famotidine, phenobarbital, supplementation, spironolactone amphotericin B, angiotensin-
potentiated sulfonamides receptor blockers (e.g.,
(e.g., sulfamethoxazole- telmisartan), azole antifungals,
trimethoprim), sulfadiazine, calcium channel blockers
terbinafine (e.g., amlodipine), cisapride,
fluoroquinolones (e.g.,
enrofloxacin), macrolide
antibiotics, metronidazole, proton
pump inhibitors (e.g., omeprazole)

Mycophenolate Amoxicillin, cephalosporins, ƒ Myelosuppression: azathioprine Salicylates (e.g., aspirin)

cholestyramine,
clindamycin,
fluoroquinolones,
furosemide, macrolide
antibiotics, metronidazole,
potentiated sulfonamides,
proton pump inhibitors,
telmisartan

Azathioprine No reported interactionsb ƒ Myelosuppression: Allopurinol, cyclophosphamide,

mycophenolate, ACE inhibitors leflunomide, sulfasalazine
(e.g., enalapril), potentiated
sulfonamides

Leflunomide Cholestyramine ƒ Hepatotoxicity: azithromycin, No reported interactionsb

amiodarone, ACE inhibitors
ACE = angiotensin-converting enzyme
a
Caution should be used when combining any pharmacologic agents. This is not an exhaustive list of interactions, and clinicians should consult a
pharmacology text.
b
Although no clinically significant interactions have been reported, this does not mean that none exist.

todaysveterinarypractice.com JULY/AUGUST 2023 91

 CONTINUING EDUCATION PEER REVIEWED

VACCINES FOR aware of the potential adverse effects, monitoring

IMMUNOCOMPROMISED PATIENTS parameters, and dose adjustments of commonly used
At this time, the full effect of immunosuppressive immunosuppressants to facilitate long-term
therapy on vaccines is unknown. Vaccine efficacy may management of immune-mediated disease.
be diminished with immunosuppressant therapy.
Evidence is lacking for appropriate vaccine strategies in
dogs and cats receiving immunosuppressive therapy. References
The decision to vaccinate should ultimately be based 1. Behrend EN, Kemppainen RJ. Glucocorticoid therapy: pharmacology,
indications, and complications. Vet Clin N Am-Small. 1997;27(2):187-
on the assessed risk for patients contracting the disease 213. doi:10.1016/s0195-5616(97)50027-1
they are vaccinated against. Owners should implement 2. Viviano KR. Glucocorticoids, cyclosporine, azathioprine, chlorambucil,
the following lifestyle modifications for dogs and cats: and mycophenolate in dogs and cats: clinical Uses, pharmacology, and
side effects. Vet Clin N Am-Small. 2022;52(3):797-817. doi:10.1016/j.
1. Avoid dog parks or boarding facilities. cvsm.2022.01.009
2. Limit exposure to heavily wooded areas (e.g., hiking, 3. Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and
management of the complications of systemic corticosteroid therapy.
swimming in rivers or lakes). Allergy Asthma Cl Im. 2013;9(1):30. doi:10.1186/1710-1492-9-30
3. Screen for feline leukemia/immunodeficiency virus 4. Dye TL, Diehl KJ, Wheeler SL, Westfall DS. Randomized,
controlled trial of budesonide and prednisone for the treatment of
before starting an immunosuppressant. Change to a idiopathic inflammatory bowel disease in dogs. J Vet Intern Med.
lifelong indoor-only lifestyle. 2013;27(6):1385-1391. doi:10.1111/jvim.12195
5. Marsilio S. Feline chronic enteropathy. J Small Anim Pract.
2021;62(6):409-419. doi:10.1111/jsap.13332
Ideally, patients diagnosed with immune-mediated
6. Pietra M, Fracassi F, Diana A, et al. Plasma concentrations and
disease should not receive routine vaccinations in order therapeutic effects of budesonide in dogs with inflammatory bowel
disease. Am J Vet Res. 2013;74(1):78-83. doi:10.2460/ajvr.74.1.78
to minimize the risk of relapse. At a minimum, patients
7. Rychlik A, Koÿodziejska-Sawerska A, Nowicki M, Szweda M. Clinical,
receiving immunosuppressants should not receive live endoscopic and histopathological evaluation of the efficacy of
or modified-live vaccines. Only core vaccines should be budesonide in the treatment of inflammatory bowel disease in dogs.
Pol J Vet Sci. 2016;19(1):159-164. doi:10.1515/pjvs-2016-0020
considered. If vaccination is deemed necessary, 8. Tumulty JW, Broussard JD, Steiner JM, Peterson ME, Williams DA.
clinicians should consider administering only 1 vaccine Clinical effects of short-term oral budesonide on the hypothalamic-
pituitary-adrenal axis in dogs with inflammatory bowel disease.
per visit, separated by several weeks. JAAHA. 2004;40(2):120-123. doi:10.5326/0400120
9. Ployngam T, Tobias AH, Smith SA, Torres SM, Ross SJ. Hemodynamic
Alternatively, annual antibody titers may be considered effects of methylprednisolone acetate administration in cats. Am J Vet
Res. 2006;67(4):583-587. doi:10.2460/ajvr.67.4.583
in lieu of routine vaccination. Many states do not 10. Ullal T, Ambrosini Y, Rao S, Webster CRL, Twedt D. Retrospective
accept titers as proof of vaccination for zoonotic evaluation of cyclosporine in the treatment of presumed idiopathic
chronic hepatitis in dogs. J Vet Intern Med. 2019;33(5):2046-2056.
diseases, specifically rabies, but waivers are available for doi:10.1111/jvim.15591
animals with medical exceptions, such as 11. Archer TM, Boothe DM, Langston VC, et al. Oral cyclosporine
treatment in dogs: a review of the literature. J Vet Intern Med.
immunosuppression.48,49 Antibody titers in cats and 2014;28(1):1-20. doi:10.1111/jvim.12265
dogs are available for rabies virus (e.g., Kansas State 12. Tauro A, Addicott D, Foale RD, et al. Clinical features of idiopathic
University, Auburn University) and for canine inflammatory polymyopathy in the Hungarian Vizsla. BMC Vet Res.
2015;11:97. doi:10.1186/s12917-015-0408-7
distemper and canine and feline parvovirus (e.g.,
13. Palmeiro BS. Cyclosporine in veterinary dermatology. Vet Clin N Am-
University of Wisconsin, Kansas State University, Small. 2013;43(1):153-171. doi:10.1016/j.cvsm.2012.09.007
Auburn University). 14. Mouatt JG. Cyclosporin and ketoconazole interaction for treatment
of perianal fistulas in the dog. Aust Vet J. 2002;80(4):207-211.
doi:10.1111/j.1751-0813.2002.tb10814.x
15. Patricelli AJ, Hardie RJ, McAnulty JF. Cyclosporine and
SUMMARY ketoconazole for the treatment of perianal fistulas in dogs. JAVMA.
2002;220(7):1009-1016. doi:10.2460/javma.2002.220.1009
Immune-mediated disease is commonly encountered in 16. Cain CL. Canine perianal fistulas. Vet Clin N Am-Small. 2019;49(1):53-
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therapeutic challenge for clinicians. Glucocorticoids are 17. Griffiths LG, Sullivan M, Borland WW. Cyclosporin as the sole
treatment for anal furunculosis: Preliminary results. J Small Anim
considered the mainstay of therapy. Clinicians should Pract. 1999;40(12):569-572. doi:10.1111/j.1748-5827.1999.tb03023.x
be aware of other immunosuppressive medications for 18. Tani A, Seno T, Yokoyama N, et al. Comparison of the efficacy of
cyclosporine and leflunomide in treating inflammatory colorectal
severe cases or cases that are refractory to glucocorticoid polyps in miniature dachshunds. J Vet Med Sci. 2020;82(4):437-440.
therapy. Choice of a second agent is largely based on doi:10.1292/jvms.19-0560
19. Grobman M, Boothe DM, Rindt H, et al. Pharmacokinetics and
anecdotal evidence or small retrospective studies. Drug dynamics of mycophenolate mofetil after single-dose oral
selection should be based on published evidence administration in juvenile dachshunds. J Vet Pharmacol Ther.
2017;40(6):e1-e10. doi:10.1111/jvp.12420
supporting the use of a certain medication as well as
patient- and client-specific factors. Clinicians should be

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20. Fukushima, K, Lappin, M, Legare, M, Veir, J. A retrospective study of 40. van Roon EN, Jansen TL, van de Laar MA, et al. Therapeutic drug
adverse effects of mycophenolate mofetil administration to dogs with monitoring of A77 1726, the active metabolite of leflunomide: serum
immune-mediated disease. J Vet Intern Med. 2021;35(5):2215-2221. concentrations predict response to treatment in patients with
doi:10.1111/jvim.16209 rheumatoid arthritis. Ann Rheum Dis. 2005;64(4):569-574. doi:10.1136/
21. Brown S, Elliott J, Francey T, Polzin D, Vaden S. Consensus ard.2004.025205
recommendations for standard therapy of glomerular disease in dogs. 41. Berg RD. Bacterial translocation from the gastrointestinal tracts of
J Vet Intern Med. 2013;27(Suppl 1):S27-S43. doi:10.1111/jvim.12230 mice receiving immunosuppressive chemotherapeutic agents. Curr
22. Ackermann AL, May ER, Frank LA. Use of mycophenolate mofetil Microbiol. 1983;8:285-292. https://doi.org/10.1007/BF01577729
to treat immune-mediated skin disease in 14 dogs—a retrospective 42. Berg RD, Wommack E, Deitch EA. Immunosuppression and
evaluation. Vet Dermatol. 2017;28(2):195-e44. doi:10.1111/vde.12400 intestinal bacterial overgrowth synergistically promote bacterial
23. Ogilvie GK, Felsburg PJ, Harris CW. Short-term effect of translocation. Arch Surg. 1988;123(11):1359-1364. doi:10.1001/
cyclophosphamide and azathioprine on selected aspects of the canine archsurg.1988.01400350073011
blastogenic response. Vet Immunol Immunopathol. 1988;18(2):119-127. 43. Kovalik M, Thoday KL, Handel IG, et al. Ciclosporin A therapy is
doi:10.1016/0165-2427(88)90054-2 associated with disturbances in glucose metabolism in dogs with
24. Dewey CW, Coates JR, Ducoté JM, Meeks JC, Fradkin JM. atopic dermatitis. Vet Dermatol. 2011;22(2):173-180. doi:10.1111/j.1365-
Azathioprine therapy for acquired myasthenia gravis in five dogs. 3164.2010.00935.x
JAAHA. 1999;35(5):396-402. doi:10.5326/15473317-35-5-396 44. Wallisch K, Trepanier LA. Incidence, timing, and risk factors of
25. Giraud L, Girod M, Cauzinille L. Combination of prednisolone and azathioprine hepatotoxicosis in dogs. J Vet Intern Med.
2015;29(2):513-518. doi:10.1111/jvim.12543
azathioprine for steroid-responsive meningitis-arteritis treatment in
dogs. JAAHA. 2021;57(1):1-7. doi:10.5326/JAAHA-MS-7019 45. Rodriguez DB, Mackin A, Easley R, et al. Relationship between red
blood cell thiopurine methyltransferase activity and myelotoxicity in
26. Scuderi MA, Snead E, Mehain S, Waldner C, Epp T. Outcome based
on treatment protocol in patients with primary canine immune- dogs receiving azathioprine. J Vet Intern Med. 2004;18(3):339-345.
mediated thrombocytopenia: 46 cases (2000-2013). Can Vet J. doi:10.1892/0891-6640(2004)18<339:rbrbct>2.0.co;2
2016;57(5):514-518. 46. IARC Working Group on the Evaluation of Carcinogenic Risks
27. Swann, JW, Garden, OA, Fellman, CL, et al. ACVIM consensus to Humans. IARC Monographs, A Review of Human Carcinogens:
statement on the treatment of immune-mediated hemolytic anemia in Pharmaceuticals. Vol 100. International Agency for Research on
dogs. J Vet Intern Med. 2019;33(3):1141-1172. doi:10.1111/jvim.15463 Cancer; 2012.

28. Mehl ML, Tell L, Kyles AE, Chen YJ, Craigmill A, Gregory CR. 47. Ohmi A, Tsukamoto A, Ohno K, et al. A retrospective study of
Pharmacokinetics and pharmacodynamics of A77 1726 and inflammatory colorectal polyps in miniature dachshunds. J Vet Med
leflunomide in domestic cats. J Vet Pharmacol Therap. Sci. 2012;74(1):59-64. doi:10.1292/jvms.11-0352
2012;35(2):139-146. doi:10.1111/j.1365-2885.2011.01306.x 48. Aubert MF. Practical significance of rabies antibodies in cats and dogs.
29. Sato M, Veir JK, Legare M, Lappin MR. A retrospective study on Rev Sci Tech. 1992;11(3):735-760. doi:10.20506/rst.11.3.622
the safety and efficacy of leflunomide in dogs. J Vet Intern Med. 49. Twark L, Dodds WJ. Clinical use of serum parvovirus and distemper
2017;31(5):1502-1507. doi:10.1111/jvim.14810 virus antibody titers for determining revaccination strategies
30. Colopy SA, Baker TA, Muir P. Efficacy of leflunomide for treatment in healthy dogs. JAVMA. 2000;217(7):1021-1024. doi:10.2460/
of immune-mediated polyarthritis in dogs: 14 cases (2006–2008). javma.2000.217.1021
JAVMA. 2010;236(3):312-318. doi:10.2460/javma.236.3.312
31. Fukushima K, Eguchi N, Ohno K, et al. Efficacy of leflunomide
for treatment of refractory inflammatory colorectal polyps in 15
miniature dachshunds. J Vet Med Sci. 2016;78(2):265-269. doi:10.1292/
jvms.15-0129
32. Stirnemann J, Kaddouri N, Khellaf M, et al. Vincristine efficacy and
safety in treating immune thrombocytopenia: a retrospective study of Stuart Walton
35 patients. Eur J Haematol. 2016;96(3):269-275. doi:10.1111/ejh.12586 Dr. Walton is a clinical assistant professor in small
33. Allen EC, Tarigo JL, LeVine DN, Barber JP, Brainard BM. Platelet animal internal medicine at the University of Florida.
number and function in response to a single intravenous dose of He received his veterinary degree at the University
vincristine. J Vet Intern Med. 2021;35(4):1754-1762. doi:10.1111/jvim.16169
of Queensland and completed 2 internal medicine
34. Scott-Moncrieff JC, Reagan WJ. Human intravenous immunoglobulin
residencies at Veterinary Specialist Services (Australia)
therapy. Semin Vet Med Surg Small Anim. 1997;12(3):178-185.
doi:10.1016/s1096-2867(97)80031-x and Louisiana State University. Dr. Walton resides in
Gainesville, Florida, where he trains students, interns,
35. Lowrie M, Thomson S, Smith P, Garosi L. Effect of a constant
rate infusion of cytosine arabinoside on mortality in dogs with and residents, promoting common-sense veterinary
meningoencephalitis of unknown origin. Vet J. 2016;213:1-5. medicine. He has a broad range of interests, including
doi:10.1016/j.tvjl.2016.03.026 infectious, inflammatory, immune-mediated, respiratory,
36. Levitin HA, Foss KD, Li Z, Reinhart JM, Hague DW, Fan TM. urinary, gastrointestinal, and hepatic diseases as well
Pharmacokinetics of a cytosine arabinoside subcutaneous protocol as extracorporeal blood purification techniques. He is
in dogs with meningoencephalomyelitis of unknown aetiology. J Vet
Pharmacol Ther. 2021;44(5):696-704. doi:10.1111/jvp.12980 the coeditor of a soon-to-be-released edition of the
Clinical Medicine of the Dog and Cat textbook and has
37. Zarfoss M, Schatzberg S, Venator K, et al. Combined cytosine
arabinoside and prednisone therapy for meningoencephalitis authored multiple articles and book chapters.
of unknown aetiology in 10 dogs. J Small Anim Pract.
2006;47(10):588-595. doi:10.1111/j.1748-5827.2006.00172.x
38. Dandrieux JRS, Noble PM, Scase TJ, Cripps PJ, German AJ. Alexis Hoelmer
Comparison of a chlorambucil-prednisolone combination with an Dr. Hoelmer is a small animal internal medicine
azathioprine-prednisolone combination for treatment of chronic
enteropathy with concurrent protein-losing enteropathy in dogs: 27
resident at the University of Florida. She received
cases (2007–2010). JAVMA. 2013;242(12):1705-1714. doi:10.2460/ her DVM degree from the University of Minnesota
javma.242.12.1705 and completed a small animal rotating internship at
39. McAtee BB, Cummings KJ, Cook AK, Lidbury JA, Heseltine JC, Willard WestVet Emergency and Specialty Hospital in Boise,
MD. Opportunistic invasive cutaneous fungal infections associated Idaho. She has a special interest in gastroenterology
with administration of cyclosporine to dogs with immune-mediated and immune-mediated disease.
disease. J Vet Intern Med. 2017;31(6):1724-1729. doi:10.1111/jvim.14824

todaysveterinarypractice.com JULY/AUGUST 2023 93

 CONTINUING EDUCATION PEER REVIEWED

CONTINUING EDUCATION

Immunosuppressant Therapy:
What, When, and Why

TOPIC OVERVIEW
This article provides an overview of commonly used immunosuppressants in
veterinary practice; outlines their efficacy, recommended doses, and how to This article has been submitted for
monitor their effectiveness; and describes potential adverse effects. Readers RACE approval for 1 hour of continuing
will also be able to identify second-line and alternative immunomodulatory education credit and will be opened for
agents, as well as alternate vaccination recommendations for the enrollment upon approval. To receive
immunocompromised patient. credit, take the test at vetfolio.com by
searching the name of the article or
LEARNING OBJECTIVES scanning the QR code below. Free
After reading this article, practitioners should be able to explain why they registration is required.
choose and start a first-line immunosuppressant and be able to identify a Questions and answers
second-line agent to use when there is refractory disease. Readers should be online may differ from
able to explain the dosing for each immunosuppressant, what monitoring is those below. Tests are
used to assess the efficacy and potential side effects of each valid for 2 years from the
immunosuppressant, what adverse side effects could occur when specific date of approval.
immunosuppressants are used, and finally answer questions regarding
vaccination of the immunocompromised patient.

1. Which immunosuppressive drug should not be 5. Which would not be an appropriate choice for
used concurrently with azathioprine due to a management of an overweight, middle-aged cat
similar mechanism of action? with inflammatory bowel disease?
a. Leflunomide a. Prednisolone
b. Mycophenolate b. Budesonide
c. Cyclosporine c. Methylprednisolone acetate
d. Budesonide d. Dexamethasone

2. Which immunosuppressive drug has been 6. Which is an indication for starting a dog with
associated with a higher risk of opportunistic immune-mediated hemolytic anemia on a second
fungal infections? immunosuppressive drug?
a. Cyclosporine a. Clinical features at presentation consistent with
b. Mycophenolate severe or immediately life-threatening disease
c. Prednisone b. Dependence on blood transfusions after 7 days
d. Azathioprine of treatment
c. Development (or expected development) of
3. True or false: Platelets evaluated after vincristine severe adverse effects related to the use of
administration have been shown to function glucocorticoids
similarly to mature platelets. d. All of the above
a. True
b. False 7. At what point after initiation of therapy with
mycophenolate would diarrhea be expected?
4. Which would be the best option for a patient a. Within 5 days
with perianal fistulas when the owner expresses b. After 1 to 2 weeks
financial constraint? c. After 3 to 4 weeks
a. Use a generic formulation of modified d. After 4 weeks
cyclosporine
b. Switch to the nonmodified formulation of 8. Which would not be an appropriate preventive
cyclosporine medicine recommendation for a dog receiving
c. Initiate concurrent use of ketoconazole with immunosuppressive therapy?
cyclosporine a. Consider performing an antibody titer for rabies
d. Switch from cyclosporine to mycophenolate virus instead of routine vaccination every 3 years

94 JULY/AUGUST 2023 todaysveterinarypractice.com

 PEER REVIEWED CONTINUING EDUCATION

b. Use a modified-live distemper/parvovirus

combination vaccine to ensure adequate
protection
c. Administer only 1 vaccine per visit, ideally spread
out by several weeks
d. Continue giving monthly flea, tick, and
heartworm preventives

9. Which statement is not appropriate regarding

tapering immunosuppressive drugs?
a. Decrease dose by no more than 25% every 2 to
4 weeks.
b. If signs of relapse are noted, increase dose
either back to previous dose or induction dose
(depending on disease severity).
c. For patients on multiple immunosuppressive
drugs, taper drugs concurrently to minimize side
effects.
d. Tapering should only be attempted once the
elisartwork/shutterstock.com

patient has been in clinical remission for at least

2 to 4 weeks.

10. Risks of therapy with multiple immunosuppressive

drugs include all of the following except:
a. Increased risk of myelosuppression
b. Increased risk of secondary infection
c. Increased risk of developing endocrine disease
d. All of the above are risks of using multiple
immunosuppressive drugs

RECONCILE® (fluoxetine hydrochloride) Chewable Tablets For complete prescribing information, see full package insert. Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.
Indications: RECONCILE chewable tablets are indicated for the treatment of canine separation anxiety in conjunction with a behavior modification plan. Contraindications: RECONCILE chewable tablets should not be used in
dogs with epilepsy or history of seizures, nor given concomitantly with drugs that lower the seizure threshold (e.g., phenothiazines). RECONCILE chewable tablets should not be given in combination with, or within 14 days of
discontinuing, a monoamine oxidase inhibitor (MAOI). RECONCILE chewable tablets are contraindicated in dogs with a known hypersensitivity to fluoxetine HCI or other SSRls. Observe a 6-week washout interval following
discontinuation of therapy with RECONCILE chewable tablets prior to the administration of any drug that may adversely interact with fluoxetine or its metabolite, norfluoxetine. Human Warnings: Not for use in humans. Keep
out of reach of children. In case of accidental ingestion seek medical attention immediately. Precautions: RECONCILE chewable tablets are not recommended for the treatment of aggression and have not been clinically tested
for the treatment of other behavioral disorders. Studies in breeding, pregnant or lactating dogs and in patients less than 6 months of age have not been conducted. Seizures may occur in dogs treated with RECONCILE chewable
tablets, even in dogs without a history of epilepsy or seizures (see Adverse Reactions). Before prescribing RECONCILE chewable tablets, a comprehensive physical examination should be conducted to rule out causes of
inappropriate behavior unrelated to separation anxiety. RECONCILE chewable tablets have not been evaluated with drugs that affect the cytochrome P450 enzyme system and should be used with caution when co-administered
with any drug that affects this system. Studies to assess the interaction of RECONCILE chewable tablets with tricyclic antidepressants (TCAs) (e.g., amitriptyline, clomipramine) have not been conducted. The minimum washout
period to transition dogs from TCAs to RECONCILE chewable tablets has not been evaluated. Data demonstrate that TCAs are cleared 4 days following discontinuation.1,2 Adverse Reactions: In two North American field studies
involving 427 dogs, the following adverse reactions were observed at a rate of ≥ 1% in dogs treated with RECONCILE chewable tablets (n=216): calm/lethargy/depression (32.9%), decreased appetite (26.9%), vomiting (17.1
%), shaking/shivering/tremor (11.1 %), diarrhea (9.7%), restlessness (7.4%), excessive vocalization (including whining) (6.0%), aggression (4.2%), otitis externa (2.8%), disorientation (2.3%), incoordination (2.3%),
constipation (1 .4%) and excessive salivation (1.4%). Other adverse reactions: Seizures: One of 112 dogs in the control group and three of 117 dogs that received RECONCILE chewable tablets experienced the serious adverse
reaction of seizures during or after the end of the treatment period. One dog that was treated with RECONCILE chewable tablets experienced two seizures 10 days after the end of therapy and, despite escalating phenobarbital
doses, died in status epilepticus approximately six months after the first seizure. In the second study, one of 99 dogs treated with RECONCILE chewable tablets and one of 99 dogs treated with the control tablet experienced the
serious adverse reaction of seizures. Lastly, in a European multi-site study, one dog treated with a daily dose of 0.4 mg/kg for one month experienced one seizure one week after discontinuing therapy. Weight loss: In field studies,
a weight loss ≥ 5% (relative to pre-study body weight) was observed in 58 (29.6%) of dogs treated with RECONCILE chewable tablets and 24 (13.0%) of control dogs. No dogs were withdrawn from clinical studies due to weight
loss alone. Dose reduction: Twenty dogs in the RECONCILE chewable tablet group and five control dogs required a dose reduction due to unacceptable adverse reactions, the majority intermittent and mild, generally anorexia,
vomiting, shaking and depression. Lowering the dose eliminated or reduced the severity of these reactions in the RECONCILE chewable tablet group only, while resumption of the full dose resulted in a return of the initial adverse
reactions in approximately half the affected dogs. One dog experienced recurrence of severe adverse reactions, which necessitated withdrawal from the study. Additionally, two dogs required a second dose reduction of RECONCILE
chewable tablets. Post Approval Experience (Rev. 2010): The following adverse events are based on post-approval adverse drug experience reporting with RECONCILE® chewable tablets. Not all adverse reactions are reported
to FDA CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data. The following adverse events are listed in decreasing order of reported
frequency: decreased appetite, depression/lethargy, shaking/shivering/tremor, vomiting, restlessness and anxiety, seizures, aggression, diarrhea, mydriasis, vocalization, weight loss, panting, confusion, incoordination and
hypersalivation. For a copy of the Safety Data Sheet (SDS) or to report suspected adverse drug events, contact Pegasus Laboratories at 1-800-874-9764. For additional information about adverse drug experience reporting for
animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae. Effectiveness: In one randomized multi-centered, double-blinded, vehicle-controlled study of 8 weeks' duration, 229 dogs were evaluated at 34
investigative sites in the United States and Canada. One hundred seventeen dogs were randomized to 1-2 mg/kg/day of RECONCILE chewable tablets and 112 dogs were randomized to the control group. Both groups underwent
concurrent behavior modification. In seven of the eight weeks, the percentage of dogs with improved overall separation anxiety scores was significantly higher (p < 0.05) among dogs treated with RECONCILE chewable tablets
compared to dogs that received the control tablet. At the end of the study, 73% of dogs treated with RECONCILE chewable tablets showed significant improvement (p=0.010) as compared to 51% of dogs treated with behavior
modification alone. Dogs treated with RECONCILE chewable tablets also showed improvement in destructive behavior, excessive vocalization and restlessness over dogs that received the control tablet. In addition, dogs in both
groups experienced improvement in inappropriate urination, inappropriate defecation, excessive salivation, excessive licking/grooming, shaking/shivering and depression. Overall separation anxiety severity scores improved
more rapidly for dogs taking RECONCILE chewable tablets than those dogs receiving the control tablet. The same effect was also noted for the individual scores for excessive vocalization and depression. To obtain full product
information please call 800-874-9764 or visit Reconcile.com • 10-2017S • Approved by FDA under NADA #141-272 • Pegasus Laboratories, Inc.

1
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