TOP 5

TOP 5 DERMATOLOGIC
INDICATIONS FOR
PENTOXIFYLLINE IN DOGS
Sarah Lewis, DVM, MS
Robert Kennis, DVM, DACVD, MS
Auburn University
PA
entoxifylline
ntemortem
is a methylxanthine
diagnosis of deriva-
tive that pancreatic
inhibits phosphodiesterase
disease is a to
raise intracellular
challenge.cyclic
Histopathol-
adenosine
monophosphate
ogy remains
levels
the
1
; this
goldcan have many
standard of
global effects, including
diagnosis improved
for pancreatic circulation
neopla-
and reduced pancreatitis.1 Pentoxifylline
inflammation.
sia and Pancreatic
inhibitsbiopsy
microvascular
providesconstriction and throm-
a definitive diag-
bus formation
nosis of
1
; increases RBCassuming
pancreatitis, and WBCadeform-
ability1;representative
decreases proinflammatory
sample is cytokine
production, neutrophil
obtained. degranulation,
An open or laparo- natural
killer cell activity,
scopic and leukocyte
approach adhesion
can be made to and
adherence to keratinocytes
collect samples. 1-3
; increases leuko-
cyte chemotaxis1; and stimulates fibroblasts to
produce collagenase and promote wound heal-
ing.1,2 Cytokines inhibited by pentoxifylline
include tumor necrosis factor-a, interferon-g,
interleukin-1 (IL-1), IL-6, IL-8, and IL-10.1

September 2015    cliniciansbrief.com    15

TOP 5  h  DERMATOLOGY   h  PEER REVIEWED

Pentoxifylline (10-30 mg/kg PO every 8 to 12

TOP 5 DERMATOLOGIC INDICATIONS hours) has a reported elimination half-life of 24
FOR PENTOXIFYLLINE to 404 minutes that supports 8-hour administra-
tion.4-6 In dogs, oral bioavailability is variable and
1. Cutaneous Vasculitis reported to be 15% to 50%.5,6 Pentoxifylline is
2. Canine Familial Dermatomyositis available as a 400-mg extended-release tablet and
is commonly halved or quartered to achieve the
3. Other Ischemic Dermatopathies
intended dosage.5,6 No controlled studies have
4. Allergic Contact Dermatitis directly investigated the pharmacokinetic effects of
breaking the extended-release tablet. Pentoxifylline
5. Atopic Dermatitis
is generally well-tolerated in dogs, and GI upset is
the most commonly reported adverse effect.5,6
Anecdotal reported use in veterinary medicine is
vast; however, peer-reviewed studies evaluating its
efficacy for the treatment of specific diseases are
limited and generally retrospective. Based on anec-
dotal evidence in human and veterinary medicine,
there is believed to be a lag in onset to clinical effect
that may last several months.6-8 Previously, con-
cerns about cost limited the use of pentoxifylline in
veterinary medicine, but affordable generic formu-
lations are now available.

Following are 5 common uses of pentoxifylline in

veterinary dermatology according to the authors.

1
dF
 IGURE 1 Multifocal to coalescing erythematous macules on the ventral
abdomen of a dog with cutaneous vasculitis. Because the lesion does not
blanch on diascopy, it is likely due to vasculitis or hemorrhage. Image Cutaneous Vasculitis
courtesy of Amelia White, Auburn University Cutaneous vasculitis refers to inflammation
of the blood vessels in the skin (Figure 1)
that results in altered blood flow and isch-
emic necrosis of the skin (Figure 2).9 The condition
may be idiopathic or caused by adverse drug reac-
tion, infection, insect bite, or neoplasia.8 Treatment
should address the underlying cause and repair tis-
sue damage.9 Pentoxifylline is an ideal treatment
(regardless of cause) because of its effect on perfu-
sion and inflammation.

Because pentoxifylline has a potential delayed

onset of effect, it is often combined with other
drugs (eg, glucocorticoids).9 In a retrospective
study,10 9 of 19 dogs with vasculitis were treated
with pentoxifylline (10-20 mg/kg PO every 12
dF
 IGURE 2 Full-thickness dermal necrosis on the hock of a patient with a
hours) alone (1 dog) or in combination (8 dogs)
neutrophilic necrotizing vasculitis suspected to be secondary to a spider
bite. Pentoxifylline (25 mg/kg PO every 12 hours) and open wound manage- with prednisone (1.5-3 mg/kg/day) with variable
ment were provided. Image courtesy of Karly Hicks, Auburn University success. Six dogs had complete resolution, 2 had

16    cliniciansbrief.com    June 2021

partial resolution, and 1 failed to respond. Of the alone or as adjunctive therapy, with a mean dosage
6 dogs with complete resolution, 3 relapsed when of 47.12 mg/kg/day PO (range, 18-112.5 mg/kg/day
prednisone was tapered, suggesting that pentoxi- PO).13 Despite common use, no difference was
fylline may be insufficient when used alone to treat found between dogs treated and dogs not treated
vasculitis.10 Insufficient dosage and frequency with pentoxifylline. It was concluded that the retro-
could explain the limited success and lack of spective nature of the study and variability in dos-
response in 3 dogs.10 Despite reports of variable ing regimens could explain this finding. Additional
success, pentoxifylline is often used for the treat- prospective, placebo-controlled studies are needed
ment of vasculitis. to determine the effectiveness of pentoxifylline in

2
the treatment of ischemic dermatopathies. Despite
Canine Familial Dermatomyositis limited evidence in the literature, the hemorrheo-
Canine familial dermatomyositis (CFD) is logic properties of pentoxifylline could be favorable
an inherited, ischemic disease of the skin, for the management of ischemic dermatopathies.
blood vessels, and muscle that predomi-
nantly affects Shetland sheepdogs and collies; how-
ever, other dog breeds can also be affected.11 Lesions
occur in the first few months of life and can vary
from minor alopecia (Figure 3) to severe dermal
ulceration and muscle atrophy. CFD is incurable;
many treatments have been attempted with limited
success. In a study, 10 dogs with CFD had partial or
complete resolution of cutaneous lesions after
receiving pentoxifylline (25 mg/kg PO every 12
hours for 12 weeks).12 The median time to initial
response was 6 weeks, supporting a lag in onset of
effect.12 No adverse effects, including clinicopatho-
logic abnormalities, were observed, further sup- dF
 IGURE 3
An alopecic, ischemic lesion on the bridge of the nose due to
porting the relative safety of pentoxifylline as dermatomyositis
compared with other therapeutic options.12

3 Other Ischemic Dermatopathies

Ischemic dermatopathy refers to several
clinical syndromes characterized by over-
all nutrient and oxygen deficiency in the
skin, including CFD, rabies-vaccine–induced
13

vasculitis, vaccine-associated ischemic dermatopa-

thy, familial cutaneous vasculopathy in German
shepherd dogs, pinnal vasculitis (Figure 4), and
idiopathic ischemic dermatopathy.13 In a study, 3
dogs with rabies-vaccine–induced vasculitis had
partial to complete hair regrowth 12 to 16 weeks
after receiving pentoxifylline (15 mg/kg PO every
12 hours) combined with prednisone (0.8-3 mg/kg/ dF
 IGURE 4 Bilaterally symmetric crusted lesions at the apex of the pinnae,
day PO).10 In a retrospective study of 177 dogs with consistent with pinnal vasculitis
ischemic dermatopathy, the majority of dogs
CFD = canine familial dermatomyositis
(91.3%) were treated with either pentoxifylline

June 2021    cliniciansbrief.com    17

TOP 5  h  DERMATOLOGY   h  PEER REVIEWED

4 Allergic Contact Dermatitis

Allergic contact dermatitis (ACD) is a type
IV hypersensitivity reaction.8,14 Reported
causes of ACD in dogs include ingestion of
mast cell degranulation and eosinophil recruitment
at the site’s wheal formation.18 These findings sug-
gest pentoxifylline may have some effect in man-
aging IgE-mediated inflammatory diseases. A
plants, topical medications, detergents, cleansers, double-blinded, placebo-controlled, crossover
fibers, and plastic.8,14 Pentoxifylline inhibits study of 10 atopic dogs showed that pentoxifylline
tumor necrosis factor-a, which is a critical media- (10 mg/kg PO every 12 hours) reduced pruritus
tor of ACD.1,14 Pentoxifylline (10 mg/kg PO every scores by 50% in one-third of dogs over 4 weeks.16
12 hours) was protective in preventing clinical Dexamethasone and pentoxifylline have an in vitro
signs in 3 dogs with known contact allergy to synergistic effect on cytokine production via human
plants in the Commelinaceae family.14 A clinical leukocytes.19 Pentoxifylline may have use as a
effect was observed within 2 days of onset of ther- steroid-sparing agent in dogs with CAD, but further
apy and persisted for 7 days following discontinua- studies are warranted to confirm its efficacy.15,16
tion of therapy.14 Treatment duration was limited
to 3 to 5 weeks due to the cost of therapy.14 Pentox- In addition to these indications, anecdotal evi-
ifylline has become less cost-prohibitive; thus, it dence suggests pentoxifylline may be useful for
can be a reasonable choice for prevention of clini- treatment of vesicular cutaneous lupus erythema-
cal signs of ACD when avoidance is not possible. tosus, erythema multiforme, acral lick dermatitis,
Major limitations of this study were the few num- and metatarsal fistulae in German shepherd dogs.8
ber of dogs included and its retrospective nature. Recent evidence evaluating the use of pentoxifyl-
Additional investigations are required to deter- line in the treatment of dermal arteritis of the
mine the effectiveness of pentoxifylline in the nasal philtrum and symmetric lupoid onychodys-
treatment of ACD. trophy suggests this drug may be an effective sole

5
or adjunctive treatment in the management of
Atopic Dermatitis these diseases.20,21 Controlled clinical studies
Canine atopic dermatitis (CAD) is a com- regarding the efficacy of pentoxifylline are lack-
mon allergic dermatosis characterized by ing. Because of its relatively affordable cost and
hypersensitivity to environmental aller- minimal adverse effects, pentoxifylline may be a
gens, primarily mediated by immunoglobulin E useful adjunct therapeutic for dermatologic condi-
(IgE).15 CAD can be challenging for the patient, pet tions in which improved microcirculation and
owner, and clinician despite available pharmaco- reduced inflammation are desired. n
logic management options. Although pentoxifyl-
ACD = allergic contact dermatitis
line is not considered a mainstay for management
CAD = canine atopic dermatitis
of CAD, limited research suggests it may have value
IgE = immunoglobulin E
as adjunctive therapy.16,17 One study in normal dogs
demonstrated that pentoxifylline inhibited late-
See page 24 for references.
phase inflammation by inhibiting IgE-mediated

Although pentoxifylline is not considered a mainstay

for management of CAD, limited research suggests it
may have value as adjunctive therapy.16,17

18    cliniciansbrief.com    June 2021

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*The clinical significance of in vitro data has not been determined.
1 Elanco Animal Health. Data on file.
2 Cole LK, Luu DH, Rajala-Schultz PJ, et al. Am J Vet Res. 2006; 67:1040-1044.
3 Farca AM, Piromalli G, Maffei F, et al. J Small Anim Pract. 1997; 38(6): 243-245. CAUTION: For topical use on dogs, cats and horses. Avoid
4 Noxon J. In: Proceedings. Central Veterinary Conference. August 26-29, 2016. Kansas City, Missouri. contact with eyes. If eye contact occurs or skin irritation develops,
5 Bloom P. In Central Veterinary Conference Proceedings. 2017.
rinse thoroughly with water, discontinue use and contact your
©2021 Elanco or its affiliates. DVM, DVM and Design, T8 Keto, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates. PM-US-21-0845 veterinarian. Available through licensed veterinarians only.
 MORE THAN JUST
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1
Elanco Animal Health. Data on file. *Malassezia and Pseudomonas.
CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. For topical use on dogs, cats and
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WARNING: Keep out of reach of children. Not for human use.
T8 Keto, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates.
©2021 Elanco or its affiliates. PM-US-21-0065(2)