MONOPRIL-HCT (fosinopril sodium-hydrochlorothiazide tablets)
has been evaluated for safety in over 660 patients with hypertension;
approximately 137 of these patients were treated for more than one year. The
observed adverse events were generally mild, transient, and similar to those
seen with fosinopril and hydrochlorothiazide taken separately. There was no
relationship between the incidence of side effects and age.
In placebo-controlled clinical trials of MONOPRIL-HCT, the
usual duration of therapy was two months. Adverse clinical or laboratory events
led to discontinuation of therapy by 4.3% of 368 placebo-treated patients and
by 3.5% of 660 MONOPRIL-HCT-treated patients.
The most common reasons for discontinuation of therapy with
MONOPRIL-HCT in U.S. studies were headache (0.3%), cough (0.3%; see PRECAUTIONS),
and fatigue (0.2%).
The side effects considered probably or possibly related to
study drug that occurred in placebo-controlled trials in more than 2% of
patients treated with MONOPRIL-HCT are shown in the table below.
Reactions Possibly or Probably Drug-Related (Incidence in
|Upper Respiratory Infection
Other side effects considered possibly or probably related
to study drug that occurred in controlled trials in 0.5% to < 2.0% of
patients treated with MONOPRIL-HCT, and rarer but clinically significant events
regardless of causal relationship were:
General: Chest pain, weakness, fever, viral
Cardiovascular: Orthostatic hypotension (seen
in 1.8% of MONOPRIL-HCT patients and 0.3% of placebo patients; no patients
discontinued therapy due to orthostatic hypotension), edema, flushing, rhythm
Dermatologic: Pruritus, rash.
Endocrine/Metabolic: Sexual dysfunction,
change in libido, breast mass.
Gastrointestinal: Nausea/vomiting, diarrhea,
dyspepsia/heartburn, abdominal pain, gastritis/esophagitis.
Immunologic: Angioedema (see WARNINGS:
Head and Neck Angioedema and Intestinal Angioedema).
Musculoskeletal: Myalgia/muscle cramps.
Respiratory: Sinus congestion, pharyngitis,
Special Senses: Tinnitus.
Urogenital: Urinary tract infection, urinary
Laboratory Test Abnormalities: Serum
electrolytes, uric acid, glucose, magnesium, cholesterol, triglycerides, and
calcium (see PRECAUTIONS). Neutropenia.
Fetal/Neonatal Morbidity and Mortality
See WARNINGS: Fetal/Neonatal Morbidity
Antihypertensive monotherapy with fosinopril has been
evaluated for safety in more than 1500 patients, of whom approximately 450
patients were treated for a year or more. The observed adverse events included
events similar to those seen with MONOPRIL-HCT; in addition, the following
others have also been reported with fosinopril:
Cardiovascular: Angina, myocardial infarction,
cerebrovascular accident, hypertensive crisis, hypotension, claudication.
Dermatologic: Urticaria, photosensitivity.
Gastrointestinal: Pancreatitis, hepatitis,
dysphagia, abdominal distention, flatulence, appetite/weight change, dry mouth.
Neurologic/Psychiatric: Memory disturbance,
tremor, confusion, mood change, sleep disturbance.
laryngitis/hoarseness, epistaxis, and (in two patients) a symptom-complex of
cough, bronchospasm, and eosinophilia.
Special Senses: Vision disturbance, taste
disturbance, eye irritation.
Urogenital: Renal insufficiency.
Laboratory Test Abnormalities: Elevations
(usually transient and minor) of BUN and creatinine have been observed, but
these have not been more frequent than in parallel patients treated with
placebo. The hemoglobin in fosinopril-treated patients generally decreases by
an average of 0.1 g/dL, but this nonprogressive change has never been
symptomatic. Leukopenia and eosinophilia have also been reported.
Serum levels of liver function tests (transaminases, LDH,
alkaline phosphatase and serum bilirubin) have occasionally been found to be
elevated, and these elevations have lead to discontinuation of therapy in 0.7%
of patients. Other risk factors for liver dysfunction have often been present
in these cases; in any event the elevations generally have resolved after
discontinuation of therapy with fosinopril.
Other Adverse Events Reported with ACE Inhibitors
Other adverse effects reported with ACE inhibitors include
cardiac arrest; pancytopenia, hemolytic anemia; aplastic anemia;
thrombocytopenia; bullous pemphigus, exfoliative dermatitis; and a syndrome
that may include one or more of arthralgia/arthritis, vasculitis, serositis,
myalgia, fever, rash or other dermopathy, positive ANA titer, leukocytosis,
eosinophilia, and elevated ESR.
Hydrochlorothiazide has now 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.
Cardiovascular: Orthostatic hypotension (may
be potentiated by alcohol, barbiturates, or narcotics).
Gastrointestinal: Pancreatitis, jaundice
(intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea,
gastric irritation, constipation, and anorexia.
Hematologic: Aplastic anemia, agranulocytosis,
leukopenia, thrombocytopenia, and hemolytic anemia.
Immunologic: Necrotizing angiitis,
Stevens-Johnson syndrome, respiratory distress (including pneumonitis and
pulmonary edema), anaphylactic reactions, purpura, urticaria, rash, and
Metabolic: Hyperglycemia, glycosuria, and
Musculoskeletal: Muscle spasm.
Neurologic: Vertigo, lightheadedness,
transient blurred vision, headache, paresthesia, xanthopsia, weakness, and