Small Animal/Exotics 20TH ANNIVERSARY Compendium December 1999
PHARM PROFILE
ENALAPRIL MALEATE
Gigi Davidson, BS, RPh
North Carolina State University
Colleen Horeish, PharmD
University of Minnesota
and its effects on blood pressure in
E
nalapril maleate is an angio- tients with severe liver dysfunction;
tensin-converting enzyme (ACE) other nonprodrug ACE inhibitors horses10 and camels11 have been stud-
inhibitor labeled to treat mild (e.g., captopril, lisinopril) would be ied. Enalapril is an effective nephro-
to severe heart failure in dogs. better choices in such patients.3 protectant in humans with chronic
renal failure,12 diabetes mellitus,13 and
PHARMACOLOGY INDICATIONS renal transplant therapy,14 although
Following oral administration, The labeling of enalapril indicates its effects in reducing proteinuria in
enalapril is converted via first-pass that it is to be used in the treatment animals require further study.
metabolism to the active metabolite of heart failure in dogs. One recent
enalaprilat, which prevents the for- study showed that enalapril in com- CAUTIONS
mation of angiotensin II (a potent bination with conventional therapy Contraindications
vasoconstrictor) by competing with (i.e., diuretics with or without digi- Enalapril should not be used in pa-
angiotensin I for the ACE. Thus the talis glycosides) produces statistically tients with a known hypersensitivity
workload of the heart is decreased as significant clinical improvement in to ACE inhibitors.
a result of both arterial and venous dogs with advanced heart failure due
dilation and decreased fluid reten- to mitral regurgitation or dilated car- Precautions
tion. diomyopathy.4 Another trial demon- Patients with severe hepatic dys-
Enalapril is well absorbed after strated the beneficial hemodynamic function are not expected to benefit
oral dosing regardless of the presence and clinical effects of adding enalapril from oral enalapril therapy because
of food in the gastrointestinal tract. to conventional therapy for dogs with they cannot convert the drug to
Enalapril’s slow onset of action (4 to CHF.5 The Long-Term Investigation enalaprilat. Ideally, renal function
6 hours) and 12- to 14-hour dura- of Veterinary Enalapril (LIVE) study (blood urea nitrogen and creatinine)
tion of action allow twice-daily dos- group also showed long-term benefit; should be determined before ACE in-
ing.1 Because the drug’s half-life and dogs treated with enalapril and con- hibitor therapy is begun, rechecked
total area under the curve are in- ventional CHF therapy survived two after 5 to 7 days of therapy, and reex-
creased in patients with renal failure times as long as did those receiving amined every 2 months thereafter.
or severe congestive heart failure standard therapy alone.6 Renal function should be checked
(CHF), dosing in those patients Enalapril has also been proven ef- more frequently in patients with azo-
should be reduced accordingly to fective in the treatment of hyperten- temia and in geriatric animals receiv-
avoid possible adverse effects.2,3 Be- sion in dogs but not in cats.7 It has ing a diuretic in conjunction with
cause enalapril is a prodrug, it will been effective in treating cardiomy- enalapril. It may be necessary to de-
not be converted to enalaprilat in pa- opathy and CHF in cats8 and ferrets,9 crease the dose and/or closely moni-
Pharm Profile introduces drugs that are new to the veterinary market as well as new indications for existing drugs. If you would like
Pharm Profile to cover a particular agent, please contact column editor Gigi Davidson, BS, RPh, North Carolina State University,
4700 Hillsborough Street, Raleigh, NC 27606; phone 919-821-9500 • fax 919-829-4225 • email gigi_davidson@[Link].
Compendium December 1999 20TH ANNIVERSARY Small Animal/Exotics
Use in Pregnancy and Neonates
Client Counseling Information Safety in breeding dogs has not
■ Try to give medication at approximately the same time(s) every day. been established. The most consistent
■ If a dose is missed, give it as soon as you remember. Do not double a birth anomalies in humans, skull hy-
dose to make up for missed doses. poplasia and renal dysfunction, ap-
■ Enalapril can be given with or without food. pear to be related more to prolonged
■ Do not alter your pet’s diet unless recommended by your veterinarian. or late-pregnancy exposure than to
Changes in salt and potassium intake may worsen your pet’s condition first-trimester exposure.26 The drug
or cause an adverse drug reaction. does cross the placenta, and traces can
■ Adverse effects with enalapril are minimal, but animals may show such be found in milk.27 Use of enalapril in
signs of gastrointestinal upset as diarrhea or vomiting. If you notice any pregnant bitches or neonates is not
adverse effects, report them to your veterinarian immediately. recommended because an intact re-
■ Your pet’s kidney function will need to be periodically monitored by nin–angiotensin system is essential to
your veterinarian while it is taking this drug, so bring your pet back in normal renal development in fetuses
for scheduled rechecks. and neonates.28
ACUTE TOXICITY
tor patients with renal, coronary, or nation with high doses of diuretics. The LD50 of enalapril in mice is
cerebrovascular insufficiency; severe Persistent cough is one of the most 2000 to 3500 mg/kg. In dogs, al-
CHF; preexisting hematologic abnor- frequent adverse effects of ACE in- though death occurred at 200 mg/kg,
malities; hyponatremia; or a collagen hibitor therapy in humans. Because no toxic effects were noted at 100
vascular disease—all of which are cough is a common symptom of mg/kg.27 In the event of an acute over-
likely to increase enalapril’s duration CHF in dogs, it is hard to discern the dose, standard gut-emptying protocols
of action. If azotemia develops or onset of an ACE-inhibitor–induced should be instituted immediately.
worsens, even after a decrease in the cough; however, there are case re- Hypotension is a major concern of
diuretic dose, the frequency of ports of enalapril-induced cough in overdosage. If noted, supportive treat-
enalapril administration should be dogs24 and a bird.25 ment and volume expansion with in-
decreased to once daily.15
Adverse Reactions
There is a strong correlation between Interested in submitting
dosage/plasma levels of enalapril and
adverse effects16: Higher blood levels an exotics article
predictably result in a higher inci-
dence of adverse effects. Increased
prostaglandin and bradykinin syn-
for Compendium?
thesis following stimulation of these
inflammatory cascades by ACE
Please contact Dr. Branson Ritchie
inhibitors has been identified as a for details (phone 706-542-6316;
possible cause of enalapril’s adverse email britchie@[Link];
effects.17,18 Gastrointestinal distress
(anorexia, vomiting, diarrhea), lethar- fax 706-542-6460).
gy, hypotension, anemia, angioede-
ma, and vasculitis have been report-
ed. 19–21 Hypotension is rare and
usually occurs when aggressive thera-
py with ACE inhibitors is begun in
volume-depleted (dehydrated) ani-
mals.22 ACE inhibitors have also been
associated with acute renal failure23;
caution should be used when admin-
istering enalapril in patients with pre-
vious renal dysfunction or in combi-
Compendium December 1999 20TH ANNIVERSARY Small Animal/Exotics
travenous sodium chloride (0.9%) should be instituted to REFERENCES
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DOSAGE AND ADMINISTRATION
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