A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Vasotec Side Effects, and Drug Interactions - Enalapril
Vasotec Side Effects, and Drug Interactions - Enalapril
SIDE EFFECTS
Tablets
Enalapril has been evaluated for safety in more than 10,000 patients,
including over 1000 patients treated for one year or more. Enalapril has
been found to be generally well tolerated in controlled clinical
trials involving 2987 patients.
For the most part, adverse experiences were mild and transient
in nature. In clinical trials,
discontinuation of therapy due to clinical
adverse experiences was required in 3.3 percent
of patients with hypertension
and in 5.7 percent of patients
with heart failure. The frequency
of adverse experiences was not related to total daily dosage
within the usual dosage ranges. In patients with hypertension
the overall percentage of patients treated with enalapril
reporting adverse experiences was comparable to placebo.
Hypertension
Adverse experiences occurring in greater than one percent
of patients with hypertension
treated with enalapril in
controlled clinical trials
are shown in TABLE 2. In patients treated with enalapril, the maximum
duration of therapy was three years; in placebo
treated patients the maximum
duration of therapy was 12 weeks.
| TABLE 2 |
| |
Vasotec (n=2314) Incidence (discontinuation) |
Placebo (n=230) Incidence |
| Body as a Whole |
| Fatigue |
3.0 (<0.1) |
2.6 |
| Orthostatic Effects |
1.2 (<0.1) |
0.0 |
| Asthenia |
1.1 (0.1) |
0.9 |
| Digestive |
| Diarrhea |
1.4 (<0.1) |
1.7 |
| Nausea |
1.4 (0.2) |
1.7 |
| Nervous/Psychiatric |
| Headache |
5.2 (0.3) |
9.1 |
| Dizziness |
4.3 (0.4) |
4.3 |
| Respiratory |
| Cough |
1.3 (0.1) |
0.9 |
| Skin |
| Rash |
1.4 (0.4) |
0.4 |
Heart Failure
Adverse experiences occurring in greater than one percent
of patients with heart failure
treated with enalapril are
shown in TABLE 3. The incidences represent the experiences from both controlled
and uncontrolled clinical trials (maximum duration
of therapy was approximately one year). In the placebo treated patients,
the incidences reported are from the controlled trials (maximum duration
of therapy is 12 weeks). The percentage of patients with severe heart
failure (NYHA Class IV) was
29 percent and 43 percent
for patients treated with enalapril
and placebo, respectively.
| TABLE 3 |
| |
Vasotec (n=673) Incidence (discontinuation) |
Placebo (n=339) Incidence |
| Body as a Whole |
| Orthostatic Effects |
2.2 (0.1) |
0.3 |
| Syncope |
2.2 (0.1) |
0.9 |
| Chest Pain |
2.1 (0.0) |
2.1 |
| Fatigue |
1.8 (0.0) |
1.8 |
| Abdominal Pain |
1.6 (0.4) |
2.1 |
| Asthenia |
1.6 (0.1) |
0.3 |
| Cardiovascular |
| Hypotension |
6.7 (1.9) |
0.6 |
| Orthostatic Hypotension |
1.6 (0.1) |
0.3 |
| Angina Pectoris |
1.5 (0.1) |
1.8 |
| Myocardial Infarction |
1.2 (0.3) |
1.8 |
| Digestive |
| Diarrhea |
2.1 (0.1) |
1.2 |
| Nausea |
1.3 (0.1) |
0.6 |
| Vomiting |
1.3 (0.0) |
0.9 |
| Nervous/Psychiatric |
| Dizziness |
7.9 (0.6) |
0.6 |
| Headache |
1.8 (0.1) |
0.9 |
| Vertigo |
1.6 (0.1) |
1.2 |
| Respiratory |
| Cough |
2.2 (0.0) |
0.6 |
| Bronchitis |
1.3 (0.0) |
0.9 |
| Dyspnea |
1.3 (0.1) |
0.4 |
| Pneumonia |
1.0 (0.0) |
2.4 |
| Skin |
| Rash |
1.3 (0.0) |
2.4 |
| Urogenital |
| Urinary Tract Infection |
1.3 (0.0) |
2.4 |
Other serious clinical adverse
experiences occurring since the drug
was marketed or adverse experiences occurring in 0.5 to 1.0 percent
of patients with hypertension
or heart failure
in clinical trials are listed
below and, within each category, are in order
of decreasing severity.
Since enalapril is converted
to enalaprilat, those adverse experiences associated with enalapril
might also be expected to occur with enalapril IV.
Body as a Whole: Anaphylactoid reactions (see PRECAUTIONS).
Cardiovascular: Cardiac arrest; myocardial
infarction or cerebrovascular
accident, possibly secondary to excessive hypotension in high risk
patients (see WARNINGS, Hypotension);
pulmonary embolism and infarction;
pulmonary edema; rhythm disturbances including atrial
tachycardia and bradycardia;
atrial fibrillation; palpitation.
Digestive: Ileus, pancreatitis, hepatitis
(hepatocellular (proven on rechallenge) or cholestatic jaundice), melena,
anorexia, dyspepsia, constipation, glossitis, stomatitis, dry mouth.
Musculoskeletal: Muscle cramps.
Nervous/Psychiatric: Depression, confusion, ataxia, somnolence,
insomnia, nervousness, peripheral
neuropathy (e.g., paresthesia, dysesthesia).
Respiratory: Bronchospasm, rhinorrhea, sore
throat and hoarseness, asthma,
upper respiratory infection, pulmonary infiltrates
Skin: Exfoliative dermatitis, toxic
epidermal necrolysis, Stevens-Johnson syndrome, herpes
zoster, erythema multiforme,
urticaria, pruritus, alopecia, flushing, diaphoresis, photosensitivity.
Special Senses: Blurred vision, taste
alteration, anosmia, tinnitus, conjunctivitis, dry eyes, tearing.
Urogenital: Renal failure, oliguria, renal
dysfunction (see PRECAUTIONS and
DOSAGE AND ADMINISTRATION) flank
pain, gynecomastia, impotence.
Miscellaneous: A symptom
complex has been reported
which may include a positive
ANA, an elevated erythrocyte
sedimentation rate,
arthralgia/arthritis, myalgia, fever, serositis, vasculitis, leukocytosis,
eosinophilia, photosensitivity, rash
and other dermatologic manifestations.
Angioedema: Angioedema has been reported in patients receiving
enalapril (0.2 percent). Angioedema associated with laryngeal
edema may be fatal. If angioedema
of the face, extremities, lips, tongue, glottis and/or larynx
occurs, treatment with enalapril
should be discontinued and appropriate therapy instituted immediately.
(See WARNINGS.)
Hypotension: In the hypertensive
patients, hypotension occurred in 0.9 percent
syncope occurred in 0.5 percent
of patients following the initial
dose or during extended therapy.
Hypotension or syncope was
a cause for discontinuation
of therapy in 0.1 percent
of hypertensive patients.
In heart failure
patients, hypotension
occurred in 6.7 percent and
syncope occurred in 2.2 percent
of patients. Hypotension or syncope
was a cause for discontinuation of therapy in 1.9 percent
of patients with heart failure.
(See WARNINGS.)
Fetal/Neonatal Morbidity and Mortality: See WARNINGS,
Fetal/Neonatal Morbidity and Mortality.
Cough: See PRECAUTIONS,
Cough.
Clinical Laboratory Test Findings
Serum Electrolytes: Hyperkalemia (see PRECAUTIONS,
Hyperkalemia).
Creatinine, Blood Urea Nitrogen: In controlled clinical
trials minor increases in blood
urea nitrogen
and serum creatinine, reversible
upon discontinuation of therapy, were observed in about 0.2 percent
of patients with essential
hypertension treated
with enalapril alone. Increases
are more likely to occur in patients receiving concomitant
diuretics or in patients with renal
artery stenosis. (See PRECAUTIONS.)
In patients with heart failure
who were also receiving diuretics with or without digitalis
increases in blood urea
nitrogen or serum
creatinine, usually reversible
upon discontinuation of enalapril
and/or other concomitant diuretic therapy, were observed in about 11 percent
of patients. Increases in blood
urea nitrogen
or creatinine were a cause
for discontinuation in 1.2 percent
of patients.
Hematology: Small decreases in hemoglobin
and hematocrit (mean decreases of approximately 0.3 g percent
and 1.0 vol percent, respectively)
occur frequently in either hypertension
or congestive heart failure
patients treated with enalapril
but are rarely of clinical
importance unless another cause of anemia
coexists. In clinical trials,
less than 0.1 percent of patients
discontinued therapy due to anemia. Hemolytic anemia, including cases
of hemolysis in patients
with G-6-PD deficiency, has been reported; a causal relationship to enalapril
has not been established.
Liver Function Tests: Elevations of liver
enzymes and/or serum bilirubin
have occurred (see WARNINGS, Hepatic Failure).
DRUG INTERACTIONS
Hypotension: Patients on Diuretic Therapy: Patients on
diuretics and especially those in whom diuretic
therapy was recently instituted, may occasionally experience
an excessive reduction of
blood pressure
after initiation of therapy with enalapril
or enalaprilat. The possibility of hypotensive effects with enalapril
or enalaprilat can be minimized by either discontinuing the diuretic
or increasing the salt intake
prior to initiation of treatment
with enalapril or enalaprilat.
If it is necessary to continue the diuretic, provide close medical
supervision after the initial
dose for at least two hours and until blood
pressure has stabilized for
at least an additional hour. (See WARNINGS
and DOSAGE AND ADMINISTRATION).
Agents Causing Renin Release: The antihypertensive
effect of enalapril and
enalapril IV
is augmented by antihypertensive
agents that cause renin release
(e.g., diuretics).
Other Cardiovascular Agents: Enalapril and enalapril
IV have been used concomitantly with beta
adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents,
hydralazine, prazosin and digoxin
without evidence of clinically significant
adverse interactions.
Enalapril IV has been used concomitantly
with digitalis without evidence
of clinically significant
adverse reactions.
Agents Increasing Serum Potassium: Enalapril and enalapril
IV attenuate potassium
loss caused by thiazide-type
diuretics. Potassium-sparing diuretics (e.g., spironolactone, triamterene,
or amiloride), potassium supplements, or potassium-containing salt
substitutes may lead to significant
increases in serum potassium.
Therefore, if concomitant
use of these agents is indicated because of demonstrated hypokalemia,
they should be used with caution and with frequent monitoring of serum
potassium. Potassium sparing agents should generally not be used in patients
with heart failure
receiving enalapril.
Lithium: Lithium toxicity has been reported in patients
receiving lithium concomitantly
with drugs which cause elimination
of sodium, including ACE inhibitors.
A few cases of lithium toxicity
have been reported in patients receiving concomitant
enalapril/enalapril IV and lithium
and were reversible upon
discontinuation of both drugs. It is recommended that serum lithium
levels be monitored frequently if enalapril
is administered concomitantly with lithium.
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