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SIDE EFFECTS
Hypertension
Quinapril HCl has been evaluated for safety in 4960 subjects
and patients. Of these, 3203 patients, including 655 elderly
patients, participated in controlled clinical trials.
Quinapril HCl has been evaluated for long-term safety
in over 1400 patients treated for 1 year or more.
Adverse experiences were usually mild and transient.
In placebo-controlled trials, discontinuation of therapy
because of adverse events was required in 4.7% of patients
with hypertension.
Adverse experiences probably or possibly related to therapy
or of unknown relationship to therapy occurring in 1%
or more of the 1563 patients in placebo-controlled hypertension
trials who were treated with quinapril HCl are shown in
TABLE 1.
| TABLE
1 Adverse Events in Placebo-Controlled Trials |
| |
Quinapril HCl |
Placebo |
| |
(N=1563) |
(N=579) |
| |
Incidence |
Incidence |
| |
(Discontinuance) |
(Discontinuance) |
| Headache |
5.6 (0.7) |
10.9 (0.7) |
| Dizziness |
3.9 (0.8) |
2.6 (0.2) |
| Fatigue |
2.6 (0.3) |
1.0 |
| Coughing |
2.0 (0.5) |
0.0 |
| Nausea and/or Vomiting |
1.4 (0.3) |
1.9 (0.2) |
| Abdominal
Pain |
1.0 (0.2) |
0.7 |
Heart Failure
Quinapril HCl has been evaluated for safety in
1222 quinapril HCl treated patients. Of these, 632 patients
participated in controlled clinical trials. In placebo-controlled
trials, discontinuation of therapy because of adverse events
was required in 6.8% of patients with congestive heart failure.
Adverse experiences probably or possibly related or of unknown
relationship to therapy occurring in 1% or more of the 585
patients in placebo-controlled congestive heart failure
trials who were treated with quinapril HCl are shown below
(TABLE 2).
| TABLE
2 |
| |
Quinapril HCl |
Placebo |
| |
(N=585) |
(N=295) |
| |
Incidence |
Incidence |
| |
(Discontinuance) |
(Discontinuance) |
| Dizziness |
7.7
(0.7) |
5.1
(1.0) |
| Coughing |
4.3
(0.3) |
1.4 |
| Fatigue |
2.6
(0.2) |
1.4 |
| Nausea
and/or vomiting |
2.4
(0.2) |
0.7 |
| Chest
Pain |
2.4 |
1.0 |
| Hypotension |
2.9
(0.5) |
1.0 |
| Dyspnea |
1.9
(0.2) |
2.0 |
| Diarrhea |
1.7 |
1.0 |
| Headache |
1.7 |
1.0
(0.3) |
| Myalgia |
1.5 |
2.0 |
| Rash |
1.4
(0.2) |
1.0 |
| Back
Pain |
1.2 |
0.3 |
See PRECAUTIONS, Cough.
Hypertension and/or Heart Failure
Clinical adverse experiences probably, possibly,
or definitely related, or of uncertain relationship
to therapy occurring in 0.5% to 1.0% (except as noted)
of the patients with CHF or hypertension treated with
quinapril HCl (with or without concomitant diuretic)
in controlled or uncontrolled trials (N=4847) and less
frequent, clinically significant events seen in clinical
trials or post-marketing experience (the rarer events
are in italics) include (listed by body system):
General: back pain, malaise, viral
infections
Cardiovascular: palpitation, vasodilation,
tachycardia, heart failure, hyperkalemia, myocardial
infarction, cerebrovascular accident, hypertensive crisis,
angina pectoris, orthostatic hypotension, cardiac rhythm
disturbances, cardiogenic shock
Hematology: hemolytic anemia
Gastrointestinal: dry mouth or throat,
constipation, gastrointestinal hemorrhage, pancreatitis,
abnormal liver function tests
Nervous/Psychiatric: somnolence, vertigo,
syncope, nervousness, depression, insomnia, paresthesia
Integumentary: alopecia, increased
sweating, pemphigus, pruritus, exfoliative dermatitis,
photosensitivity reaction, dermatopolymiositis
Urogenital: imotenceacute renal failure,
worsening renal failure
Respiratory: eosinophilic pneumonitis
Other: amblyopia, pharyngitisagranulocytosis,
hepatitis, thrombocytopenia
Fetal/Neonatal Morbidity and Mortality
See WARNINGS, Fetal/Neonatal Morbidity
and Mortality.
Angioedema
Angioedema has been reported in patients receiving
quinapril HCl (0.1%). Angioedema associated with laryngeal
edema may be fatal. If angioedema of the face, extremities,
lips, tongue, glottis, and/or larynx occurs, treatment
with quinapril HCl should be discontinued and appropriate
therapy instituted immediately. (See WARNINGS.)
Clinical Laboratory Test Findings
Hematology: (See WARNINGS)
Hyperkalemia: (See PRECAUTIONS)
Creatinine and Blood Urea Nitrogen:
Increases (>1.25 times the upper limit of normal)
in serum creatinine and blood urea nitrogen were observed
in 2% and 2%, respectively, of all patients treated
with quinapril HCl alone. Increases are more likely
to occur in patients receiving concomitant diuretic
therapy than in those on quinapril HCl alone. These
increases often remit on continued therapy. In controlled
studies of heart failure, increases in blood urea nitrogen
and serum creatinine were observed in 11% and 8%, respectively,
of patients treated with quinapril HCl; most often these
patients were receiving diuretics with or without digitalis.
DRUG INTERACTIONS
Concomitant Diuretic Therapy: As with other
ACE inhibitors, patients on diuretics, especially those
on recently instituted diuretic therapy, may occasionally
experience an excessive reduction of blood pressure
after initiation of therapy with quinapril HCl. The
possibility of hypotensive effects with quinapril HCl
may be minimized by either discontinuing the diuretic
or cautiously increasing salt intake prior to initiation
of treatment with quinapril HCl. If it is not possible
to discontinue the diuretic, the starting dose of quinapril
should be reduced (see DOSAGE AND ADMINISTRATION.)
Agents Increasing Serum Potassium:
Quinapril can attenuate potassium loss caused by thiazide
diuretics and increase serum potassium when used alone.
If concomitant therapy of quinapril HCl with potassium-sparing
diuretics (e.g., spironolactone, triamterene, or amiloride),
potassium supplements, or potassium-containing salt
substitutes is indicated, they should be used with caution
along with appropriate monitoring of serum potassium
(see PRECAUTIONS.)
Tetracycline and Other Drugs that Interact
with Magnesium: Simultaneous administration
of tetracycline with quinapril HCl reduced the absorption
of tetracycline by approximately 28% to 37%, possibly
due to the high magnesium content in quinapril HCl tablets.
This interaction should be considered if coprescribing
quinapril HCl and tetracycline or other drugs that interact
with magnesium.
Lithium: Increased serum lithium levels
and symptoms of lithium toxicity have been reported
in patients receiving concomitant lithium and ACE inhibitor
therapy. These drugs should be coadministered with caution
and frequent monitoring of serum lithium levels is recommended.
If a diuretic is also used, it may increase the risk
of lithium toxicity.
Other Agents: Drug interaction studies
of quinapril HCl with other agents showed:
- Multiple dose therapy with propranolol
or cimetidine has no effect on the pharmacokinetics
of single doses of quinapril HCl.
- The anticoagulant effect of a single
dose of warfarin (measured by prothrombin time) was
not significantly changed by quinapril coadministration
twice-daily.
- Quinapril HCl treatment did not
affect the pharmacokinetics of digoxin.
- No pharmacokinetic interaction
was observed when single doses of quinapril HCl and
hydrochlorothiazide were administered concomitantly.
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