PRINZIDE has been evaluated for safety in 930 patients,
including 100 patients treated for 50 weeks or more.
In clinical trials with PRINZIDE no adverse experiences
peculiar to this combination drug have been observed. Adverse experiences that
have occurred have been limited to those that have been previously reported
with lisinopril or hydrochlorothiazide.
The most frequent clinical adverse experiences in controlled
trials (including open label extensions) with any combination of lisinopril and
hydrochlorothiazide were: dizziness (7.5 percent), headache (5.2 percent),
cough (3.9 percent), fatigue (3.7 percent) and orthostatic effects (3.2
percent), all of which were more common than in placebo-treated patients.
Generally, adverse experiences were mild and transient in nature; but see WARNINGS
regarding angioedema and excessive hypotension or syncope. Discontinuation of
therapy due to adverse effects was required in 4.4 percent of patients, principally
because of dizziness, cough, fatigue and muscle cramps.
Adverse experiences occurring in greater than one percent of
patients treated with lisinopril plus hydrochlorothiazide in controlled
clinical trials are shown below.
||Percent of Patients
in Controlled Studies
|Upper Respiratory Infection
Clinical adverse experiences occurring in 0.3 to 1.0 percent
of patients in controlled trials included: Body as a Whole: Chest pain,
abdominal pain, syncope, chest discomfort, fever, trauma, virus infection. Cardiovascular:
Palpitation, orthostatic hypotension. Digestive: Gastrointestinal cramps, dry
mouth, constipation, heartburn. Musculoskeletal: Back pain, shoulder
pain, knee pain, back strain, myalgia, foot pain. Nervous/Psychiatric: Decreased
libido, vertigo, depression, somnolence. Respiratory: Common cold, nasal
congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary
congestion, chronic sinusitis, allergic rhinitis, pharyngeal discomfort. Skin:
Flushing, pruritus, skin inflammation, diaphoresis. Special Senses: Blurred
vision, tinnitus, otalgia. Urogenital: Urinary tract infection.
Angioedema has been reported in patients receiving PRINZIDE,
with an incidence higher in Black than in non-Black patients. Angioedema
associated with laryngeal edema may be fatal. If angioedema of the face,
extremities, lips, tongue, glottis and/or larynx occurs, treatment with
PRINZIDE should be discontinued and appropriate therapy instituted immediately.
In rare cases, intestinal angioedema has been reported with angiotensin
converting enzyme inhibitors including lisinopril. (See WARNINGS.)
In clinical trials, adverse effects relating to hypotension
occurred as follows: hypotension (1.4), orthostatic hypotension (0.5), other
orthostatic effects (3.2). In addition syncope occurred in 0.8 percent of
patients. (See WARNINGS.)
See PRECAUTIONS, Cough.
Clinical Laboratory Test Findings
Serum Electrolytes: See PRECAUTIONS.
Creatinine, Blood Urea Nitrogen: Minor reversible
increases in blood urea nitrogen and serum creatinine were observed in patients
with essential hypertension treated with PRINZIDE. More marked increases have
also been reported and were more likely to occur in patients with renal artery
stenosis. (See PRECAUTIONS.)
Serum Uric Acid, Glucose, Magnesium, Cholesterol,
Triglycerides and Calcium: See PRECAUTIONS. Hemoglobin and
Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately
0.5 g percent and 1.5 vol percent, respectively) occurred frequently in
hypertensive patients treated with PRINZIDE but were rarely of clinical
importance unless another cause of anemia coexisted. In clinical trials, 0.4
percent of patients discontinued therapy due to anemia.
Liver Function Tests: Rarely, elevations of liver
enzymes and/or serum bilirubin have occurred (see WARNINGS, Hepatic
Other adverse reactions that have been reported with the
individual components are listed below
In clinical trials adverse reactions
which occurred with lisinopril were also seen with PRINZIDE. In addition, and
since lisinopril has been marketed, the following adverse reactions have been reported
with lisinopril and should be considered potential adverse reactions for
PRINZIDE: Body as a Whole: Anaphylactoid reactions (see WARNINGS,
Anaphylactoid and Possibly Related Reactions), malaise, edema, facial
edema, pain, pelvic pain, flank pain, chills; Cardiovascular: Cardiac
arrest, myocardial infarction or cerebrovascular accident, possibly secondary
to excessive hypotension in highrisk patients (see WARNINGS, Hypotension),
pulmonary embolism and infarction, worsening of heart failure, arrhythmias
(including tachycardia, ventricular tachycardia, atrial tachycardia, atrial
fibrillation, bradycardia, and premature ventricular contractions), angina
pectoris, transient ischemic attacks, paroxysmal nocturnal dyspnea, decreased
blood pressure, peripheral edema, vasculitis; Digestive: Pancreatitis,
hepatitis (hepatocellular or cholestatic jaundice) (see WARNINGS, Hepatic
Failure), gastritis, anorexia, flatulence, increased salivation; Endocrine:
Diabetes mellitus, syndrome of inappropriate antidiuretic hormone secretion
(SIADH); Hematologic: Rare cases of neutropenia, thrombocytopenia, and
bone marrow depression have been reported. Hemolytic anemia has been reported;
a causal relationship to lisinopril cannot be excluded; Metabolic: Gout,
weight loss, dehydration, fluid overload, weight gain; Musculoskeletal: Arthritis,
arthralgia, neck pain, hip pain, joint pain, leg pain, arm pain, lumbago; Nervous
System/Psychiatric: Ataxia, memory impairment, tremor, insomnia, stroke, nervousness,
confusion, peripheral neuropathy (e.g., paresthesia, dysesthesia), spasm,
hypersomnia, irritability; Respiratory: Malignant lung neoplasms,
hemoptysis, pulmonary edema, pulmonary infiltrates, eosinophilic pneumonitis,
bronchospasm, asthma, pleural effusion, pneumonia, wheezing, orthopnea, painful
respiration, epistaxis, laryngitis, sinusitis, pharyngitis, rhinitis,
rhinorrhea, chest sound abnormalities; Skin: Urticaria, alopecia, herpes
zoster, photosensitivity, skin lesions, skin infections, pemphigus, erythema.
Other severe skin reactions (including toxic epidermal necrolysis, Stevens- Johnson
syndrome and cutaneous pseudolymphoma) have been reported rarely; causal
relationship has not been established; Special Senses: Visual loss,
diplopia, photophobia, taste disturbances; Urogenital: Acute renal
failure, oliguria, anuria, uremia, progressive azotemia, renal dysfunction (see
PRECAUTIONS and DOSAGE AND ADMINISTRATION), pyelonephritis,
dysuria, breast pain.
A symptom complex has been reported which may include a
positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis,
myalgia, fever, vasculitis, leukocytosis, eosinophilia, photosensitivity, rash,
and other dermatological manifestations.
Fetal/Neonatal Morbidity and Mortality
See WARNINGS, Pregnancy, Lisinopril, Fetal/Neonatal
Morbidity and Mortality.
Body as a Whole: Weakness;
Digestive: Anorexia, gastric irritation, cramping, jaundice
(intrahepatic cholestatic jaundice), pancreatitis, sialadenitis, constipation; Hematologic:
Leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic
anemia; Musculoskeletal: Muscle spasm; Nervous System/Psychiatric:
Restlessness; Renal: Renal failure, renal dysfunction, interstitial
nephritis (see WARNINGS); Skin: Erythema multiforme including
Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal
necrolysis, alopecia; Special Senses: Xanthopsia; Hypersensitivity:
Purpura, photosensitivity, urticaria, necrotizing
angiitis (vasculitis and
cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary
edema, anaphylactic reactions.