ADVERSE REACTIONS
Quinapril hydrochloride
and hydrochlorothiazide has been evaluated for safety in 1571 patients in
controlled and uncontrolled studies. Of these, 498 were given quinapril plus
hydrochlorothiazide for at least 1 year, with 153 patients extending combination
therapy for over 2 years. In clinical trials with quinapril hydrochloride and
hydrochlorothiazide, no adverse experience specific to the combination has been
observed. Adverse experiences that have occurred have been limited to those that
have been previously reported with quinapril or hydrochlorothiazide.
Adverse experiences were
usually mild and transient, and there was no relationship between side effects
and age, sex, race, or duration of therapy. Discontinuation of therapy because
of adverse effects was required in 2.1% in patients in controlled studies. The
most common reasons for discontinuation of therapy with quinapril hydrochloride
and hydrochlorothiazide were cough (1%; see PRECAUTIONS)
and headache (0.7%).
Adverse experiences
probably or possibly related to therapy or of unknown relationship to therapy
occurring in 1% or more of the 943 patients treated with quinapril plus
hydrochlorothiazide in controlled trials are shown below.
| |
Percent of Patients in Controlled
Trials |
| |
Quinapril/ HCTZ N = 943 |
Placebo N = 100 |
| Headache |
6.7 |
30 |
| Dizziness |
4.8 |
4 |
| Coughing |
3.2 |
2 |
| Fatigue |
2.9 |
3 |
| Myalgia |
2.4 |
5 |
| Viral Infection |
1.9 |
4 |
| Rhinitis |
2 |
3 |
| Nausea and/or Vomiting |
1.8 |
6 |
| Abdominal Pain |
1.7 |
4 |
| Back Pain |
1.5 |
2 |
| Diarrhea |
1.4 |
1 |
| Upper Respiratory Infection |
1.3 |
4 |
| Insomnia |
1.2 |
2 |
| Somnolence |
1.2 |
0 |
| Bronchitis |
1.2 |
1 |
| Dyspepsia |
1.2 |
2 |
| Asthenia |
1.1 |
1 |
| Pharyngitis |
1.1 |
2 |
| Vasodilatation |
1 |
1 |
| Vertigo |
1 |
2 |
| Chest Pain |
1 |
2 |
Clinical adverse
experiences probably, possibly, or definitely related or of uncertain
relationship to therapy occurring in greater than or equal to 0.5% to less than 1% (except as noted) of the
patients treated with quinapril/HCTZ in controlled and uncontrolled trials (N =
1571) and less frequent, clinically significant events seen in clinical trials
or postmarketing experience (the rarer events are in italics) include (listed by
body system):
| BODY AS A WHOLE: |
Asthenia, Malaise |
| CARDIOVASCULAR: |
Palpitation, Tachycardia, Heart Failure,
Hyperkalemia,
|
| |
Myocardial Infarction, Cerebrovascular
Accident,
|
| |
Hypertensive Crisis, Angina Pectoris,
Orthostatic
|
| |
Hypotension, Cardiac Rhythm
Disturbance
|
| GASTROINTESTINAL: |
Mouth or Throat Dry, Gastrointestinal
Hemorrhage,
|
| |
Pancreatitis, Abnormal Liver Function
Tests
|
| NERVOUS/PSYCHIATRIC: |
Nervousness, Vertigo, Paresthesia
|
| RESPIRATORY: |
Sinusitis, Dyspnea |
| INTEGUMENTARY: |
Pruritus, Sweating Increased, Erythema
Multiforme,
|
| |
Exfoliative Dermatitis, Photosensitivity
Reaction, Alopecia,
|
| |
Pemphigus
|
| UROGENITAL SYSTEM: |
Acute Renal Failure,
Impotence
|
| OTHER: |
Agranulocytosis, Thrombocytopenia,
Arthralgia
|
| Angioedema: |
Angioedema has been reported in 0.1% of patients receiving
|
| |
quinapril (0.1%) (see WARNINGS).
|
| Fetal/Neonatal Morbidity and |
See WARNINGS: Fetal/Neonatal
|
| Mortality: |
Morbidity and Mortality |
Postmarketing Experience
The following serious
nonfatal adverse events, regardless of their relationship to quinapril and HCTZ
combination tablets, have been reported during extensive postmarketing
experience:
BODY AS A WHOLE: Shock,
accidental injury, neoplasm, cellulitis, ascites, generalized edema, hernia and
anaphylactoid reaction.
CARDIOVASCULAR SYSTEM:
Bradycardia, cor pulmonale, vasculitis, and deep thrombosis.
DIGESTIVE SYSTEM:
Gastrointestinal carcinoma, cholestatic jaundice, hepatitis, esophagitis,
vomiting, and diarrhea.
HEMIC SYSTEM:
Anemia.
METABOLIC AND
NUTRITIONAL DISORDERS: Weight loss.
MUSCULOSKELETAL SYSTEM:
Myopathy, myositis, and arthritis.
NERVOUS SYSTEM:
Paralysis, hemiplegia, speech disorder, abnormal gait, meningism, and
amnesia.
RESPIRATORY SYSTEM:
Pneumonia, asthma, respiratory infiltration, and lung disorder.
SKIN AND APPENDAGES:
Urticaria, macropapular rash, and petechiases.
SPECIAL SENSES: Abnormal
vision.
UROGENITAL SYSTEM:
Kidney function abnormal, albuminuria, pyuria, hematuria, and nephrosis.
Quinapril monotherapy
has been evaluated for safety in 4960 patients. In clinical trials adverse
events which occurred with quinapril were also seen with quinapril hydrochloride
and hydrochlorothiazide. In addition, the following were reported for quinapril
at an incidence greater than 0.5%: depression, back pain, constipation, syncope, and
amblyopia.
Hydrochlorothiazide has
been extensively prescribed for many years, but there has not been enough
systematic collection of data to support an estimate of the frequency of the
observed adverse reactions. Within organ-system groups, the reported reactions
are listed here in decreasing order of severity, without regard to frequency.
| BODY AS A WHOLE: |
Weakness. |
| CARDIOVASCULAR: |
Orthostatic hypotension (may be potentiated by alcohol,
|
| |
barbiturates, or narcotics). |
| DIGESTIVE: |
Pancreatitis, jaundice (intrahepatic cholestatic),
sialadenitis, |
| |
vomiting, diarrhea, cramping, nausea, gastric irritation,
|
| |
constipation, and anorexia. |
| NEUROLOGIC: |
Vertigo, lightheadedness, transient blurred vision, headache,
|
| |
paresthesia, xanthopsia, weakness, and restlessness.
|
| MUSCULOSKELETAL: |
Muscle spasm. |
| HEMATOLOGIC: |
Aplastic anemia, agranulocytosis, leukopenia, |
| |
thrombocytopenia, and hemolytic anemia. |
| RENAL: |
Renal failure, renal dysfunction, interstitial nephritis
|
| |
(see WARNINGS). |
| METABOLIC: |
Hyperglycemia, glycosuria, and hyperuricemia. |
| HYPERSENSITIVITY: |
Necrotizing angiitis, Stevens-Johnson syndrome, |
| |
respiratory distress (including pneumonitis and |
| |
pulmonary edema), purpura, urticaria, rash, and |
| |
photosensitivity. |
Clinical Laboratory Test Findings
Serum
Electrolytes: See PRECAUTIONS.
Creatinine, Blood Urea Nitrogen: Increases (greater than 1.25 times
the upper limit of normal) in serum creatinine and blood urea nitrogen were
observed in 3% and 4%, respectively, of patients treated with quinapril
hydrochloride and hydrochlorothiazide. Most increases were minor and reversible,
which can occur in patients with essential hypertension but most frequently in
patients with renal artery stenosis (see PRECAUTIONS).
PBI and
Tests of Parathyroid Function: See PRECAUTIONS.
Hematology: See WARNINGS.
Other
(causal relationships unknown): Other clinically important changes in
standard laboratory tests were rarely associated with quinapril hydrochloride
and hydrochlorothiazide administration. Elevations in uric acid, glucose,
magnesium, cholesterol, triglyceride, and calcium (see PRECAUTIONS) have been reported.
|
