Monopril HCT

Fosinopril sodium is a white to off-white crystalline powder, soluble ( > 100 mg/mL) in water, in ethanol, and in methanol, and slightly soluble in hexane. Fosinopril sodium is designated chemically as L-proline, 4-cyclohexyl-1-[[[2-methyl-1-(1-oxopropoxy)propoxy](4-phenylbutyl)phosphinyl]acetyl]-, sodium salt, trans-; its structural formula is:

Its empirical formula is C30H45NNaO7P, and its molecular weight is 585.65.

Fosinoprilat, the active metabolite of fosinopril, is a non-sulfhydryl angiotensin-converting enzyme inhibitor. Fosinopril is converted to fosinoprilat by hepatic cleavage of the ester group.

Hydrochlorothiazide, USP is a white, or practically white, practically odorless, crystalline powder. It is slightly soluble in water; freely soluble in sodium hydroxide solution, in n-butylamine, and in dimethylformamide; sparingly soluble in methanol; and insoluble in ether, in chloroform, and in dilute mineral acids. Hydrochlorothiazide is designated chemically as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; its structural formula is:

Its empirical formula is C7H8ClN3O4S2, and its molecular weight is 297.73. Hydrochlorothiazide is a thiazide diuretic.

MONOPRIL®-HCT (fosinopril sodium-hydrochlorothiazide tablets) is a combination of fosinopril sodium and hydrochlorothiazide, USP. It is available for oral use in two tablet strengths: MONOPRIL-HCT 10/12.5, containing 10 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide, USP; and MONOPRIL-HCT 20/12.5, containing 20 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide, USP. The inactive ingredients of the tablets include lactose, croscarmellose sodium, povidone, sodium stearyl fumarate, and iron oxide.

MONOPRIL-HCT (fosinopril sodium-hydrochlorothiazide tablets) is indicated for the treatment of hypertension.

These fixed dose combinations are not indicated for initial therapy. (See DOSAGE AND ADMINISTRATION.)

In using MONOPRIL-HCT, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that fosinopril does not have a similar risk (see WARNINGS: Neutropenia/Agranulocytosis).

ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients (see WARNINGS: Head and Neck Angioedema and Intestinal Angioedema).

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 Placebo-Controlled Studies)

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 infection.

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 disturbance, syncope.

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.

Neurologic/Psychiatric: Somnolence, depression, numbness/paresthesia.

Respiratory: Sinus congestion, pharyngitis, rhinitis.

Special Senses: Tinnitus.

Urogenital: Urinary tract infection, urinary frequency, dysuria.

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 and Mortality.

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.

Endocrine/Metabolic: Gout.

Gastrointestinal: Pancreatitis, hepatitis, dysphagia, abdominal distention, flatulence, appetite/weight change, dry mouth.

Hematologic: Lymphadenopathy.

Musculoskeletal: Arthralgia.

Neurologic/Psychiatric: Memory disturbance, tremor, confusion, mood change, sleep disturbance.

Respiratory: Bronchospasm, 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 photosensitivity.

Metabolic: Hyperglycemia, glycosuria, and hyperuricemia.

Musculoskeletal: Muscle spasm.

Neurologic: Vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness.

Mechanism of Action

Fosinopril and fosinoprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and in animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. Hypertensive patients treated with fosinopril alone for an average of 8 weeks had elevations of serum potassium of approximately 0.1 mEq/L. Similar patients treated with hydrochlorothiazide alone had a mean reduction in serum potassium of 0.15 mEq/L, while patients who received combined treatment with 10/12.5 mg or 20/12.5 mg of fosinopril and hydrochlorothiazide had reductions of 0.07 and 0.03 mEq/L, respectively. (See PRECAUTIONS.)

Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of MONOPRIL-HCT (fosinopril sodium-hydrochlorothiazide tablets) remains to be elucidated.

While the mechanism through which fosinopril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, fosinopril has an antihypertensive effect even in patients with low-renin hypertension.

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin, so coadministration of an ACE inhibitor tends to reverse the potassium loss associated with these diuretics.

The mechanism of the antihypertensive effect of thiazides is unknown.

Pharmacokinetics and Metabolism

The absolute absorption of fosinopril averages 36% of an oral dose. The primary site of absorption is the proximal small intestine. While the rate of absorption may be slowed by the presence of food in the gastrointestinal tract, the extent of absorption of fosinopril is essentially unaffected.

Following oral administration of hydrochlorothiazide, peak plasma concentrations are achieved in 1–2.5 hours, and the extent of absorption is 50–80%. The reported studies of food effects on hydrochlorothiazide absorption have been inconclusive. The absorption of hydrochlorothiazide is increased by agents that reduce gastrointestinal motility. It is reported to be decreased by 50% in patients with congestive heart failure.

Cleavage of the ester group (primarily in the liver) converts fosinopril to its active metabolite, fosinoprilat. The time to peak plasma concentrations of fosinoprilat is about 3 hours, independent of the administered dose of fosinopril. In patients with hepatic dysfunction due to cirrhosis, conversion of fosinopril to fosinoprilat may be slowed, but the extent of this conversion is unchanged.

Fosinoprilat is highly protein bound (95%), but has negligible binding to cellular components of blood. The peak serum concentration and the area under the concentration-time curve of fosinoprilat is directly proportional to the administered dose of fosinopril.

After an oral dose of radiolabeled fosinopril, 75% of radioactivity in plasma was present as active fosinoprilat, 20–30% as a glucuronide conjugate of fosinoprilat, and 1–5% as a p-hydroxy metabolite of fosinoprilat. Since fosinoprilat is not biotransformed after intravenous administration, fosinopril, not fosinoprilat, appears to be the precursor for the glucuronide and p-hydroxy metabolites. In rats, the p-hydroxy metabolite of fosinoprilat is as potent an inhibitor of ACE as fosinoprilat; the glucuronide conjugate is devoid of ACE inhibitory activity.

Studies in animals indicate that fosinopril and fosinoprilat do not cross the blood-brain barrier, but fosinoprilat does cross the placenta of pregnant animals. In humans, hydrochlorothiazide crosses the placenta freely, and levels in umbilical-cord blood are similar to those in the maternal circulation.

Hydrochlorothiazide is not metabolized. Its apparent volume of distribution is 3.6–7.8 L/kg, and its measured plasma protein binding is 67.9%. The drug also accumulates in red blood cells, so that whole blood levels are 1.6–1.8 times those measured in plasma.

After intravenous administration, fosinoprilat is eliminated approximately equally by the liver and kidney. After oral administration of radiolabeled fosinopril, approximately half of the absorbed dose is excreted in the urine and the remainder is excreted in the feces. In two studies involving healthy subjects, the mean body clearance of intravenous fosinoprilat was between 26 and 39 mL/min.

In hypertensive patients with normal renal and hepatic function, the effective half-life of accumulation of fosinoprilat following multiple dosing of fosinopril sodium is 11.5 hours. Thus, steady-state concentrations of fosinoprilat should be reached after 2 or 3 doses of MONOPRIL-HCT given once daily.

In patients with renal insufficiency (creatinine clearance < 80 mL/min/1.73 m²), the total body clearance of fosinoprilat is approximately one half of that in patients with normal renal function, while absorption, bioavailability, and protein binding are not appreciably altered. The clearance of fosinoprilat does not differ appreciably with the degree of renal insufficiency, because the diminished renal elimination is offset by increased hepatobiliary elimination. A modest increase in plasma AUC levels (less than two times that in normals) was observed in patients with various degrees of renal insufficiency, including end-stage renal failure (creatinine clearance < 10 mL/min/1.73 m²). (See DOSAGE AND ADMINISTRATION.)

Fosinopril is not well dialyzed. Clearance of fosinoprilat by hemodialysis and peritoneal dialysis averages 2% and 7%, respectively, of urea clearances.

In patients with hepatic insufficiency (alcoholic or biliary cirrhosis), the apparent total body clearance of fosinoprilat is approximately one half of that in patients with normal hepatic function.

In elderly (male) subjects (65–74 years old) with clinically normal renal and hepatic function, there appear to be no significant differences in pharmacokinetic parameters for fosinoprilat compared to those of younger subjects (20–35 years old).

Thiazide diuretics are eliminated by the kidney, with a terminal half-life of 5–15 hours. In a study of patients with impaired renal function (mean creatinine clearance of 19 mL/min), the half-life of hydrochlorothiazide elimination was lengthened to 21 hours.

When fosinopril and hydrochlorothiazide are administered concomitantly, the pharmacokinetics of hydrochlorothiazide are essentially unaffected. Serum levels of fosinoprilat are increased after several weeks of coadministration of hydrochlorothiazide and fosinopril, but the increase is not sufficient to warrant any change in dosing.

Pharmacodynamics

After single doses of 10–40 mg of fosinopril, serum ACE activity was inhibited by at least 90% from 2–12 hours after dosing. At 24 hours, serum ACE activity remains suppressed by 85–93%.

Administration of fosinopril to patients with mild to moderate hypertension results in a reduction of both supine and standing blood pressure to about the same extent with no compensatory tachycardia. In studies in hypertensive patients after three months of fosinopril monotherapy, hemodynamic responses to various stimuli (isometric exercise, 45° head-up tilt, mental challenges) were unchanged compared to baseline, suggesting that fosinopril did not affect the activity of the sympathetic nervous system. Instead, fosinopril-induced reduction in blood pressure appears to be mediated by a reduction in peripheral vascular resistance without reflex cardiac effects. In similar studies, renal, splanchnic, cerebral, and skeletal-muscle blood flows were all unchanged compared to baseline, as was glomerular filtration rate. Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt- and/or volume-depleted (see WARNINGS).

Following oral administration of single doses of 10–40 mg, fosinopril lowered blood pressure within one hour, with peak reductions achieved 2–6 hours after dosing. The antihypertensive effect of a single dose persisted for 24 hours. Following four weeks of monotherapy in placebo-controlled trials in patients with mild to moderate hypertension, once-daily doses of 20–80 mg lowered supine or seated blood pressures (systolic/diastolic) 24 hours after dosing by an average of 8–9/6–7 mmHg more than placebo. The trough effect was about 50–60% of the peak diastolic response and about 80% of the peak systolic response.

In clinical studies of various combinations that included 0–40 mg of fosinopril and 0–37.5 mg of hydrochlorothiazide, the antihypertensive effects were increased with increasing dose of either component. Peak blood pressure reductions were achieved 2–6 hours after dosing. The mean reductions in seated blood pressure (systolic/diastolic) associated with MONOPRIL-HCT (fosinopril sodium-hydrochlorothiazide tablets) 10/12.5 after 24 hours were 9–18/5–7 mmHg greater than those associated with placebo; those associated with MONOPRIL-HCT 20/12.5 after 24 hours were 12–17/8–10 mmHg greater than those associated with placebo. These trough effects were 60–90% of the corresponding peak effects.

Although hydrochlorothiazide tends to be more effective in low-renin hypertensive patients (mainly blacks), and fosinopril—like other ACE inhibitors—tends to be more effective in high-renin patients (mainly non-blacks), the effectiveness of MONOPRIL-HCT is independent of race, age, and gender.

Monopril HCT is a prescription medication used to treat high blood pressure. It is a single product containing 2 medications: fosinopril and hydrochlorothiazide. Fosinopril belongs to a group of drugs called angiotensin-converting enzyme (ACE) inhibitors. Fosinopril works by blocking the ACE enzyme, which helps blood vessels to relax and lowers blood pressure. Hydrochlorothiazide belongs to a group of drugs called thiazide diuretics, which work by stopping reabsorption of salt into your body. This prevents fluid from building up in the body.

This medication comes in tablet form and is typically given once daily with or without food.

Common side effects of Monopril HCT include headache, cough, and upper respiratory infections. 

Monopril HCT can also cause tiredness (fatigue) and dizziness. Do not drive or operate heavy machinery until you know how Monopril HCT affects you.

This brand is no longer available, but the generic, fosinopril and hydrochlorothiazide, is available. 

Before taking Monopril HCT, tell your doctor about all of your medical conditions. Especially tell your doctor if:

• you are allergic to fosinopril, to any other ACE inhibitor, to hydrochlorothiazide, or other sulfonamide-derived drugs, or any other ingredient in Monopril HCT
• your kidneys are unable to produce urine (anuric)
• you have kidney or liver disease
• you have diabetes, especially if you are taking aliskiren (Tekturna)
• you are about to have major surgery
• you are pregnant or plan to become pregnant
• you are breastfeeding or plan to breastfeed

Tell you doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. 

Hydrochlorothiazide is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

Fosinopril is an ACE inhibitor. ACE stands for angiotensin converting enzyme. Fosinopril lowers blood pressure and also relieves symptoms of fluid retention.

Hydrochlorothiazide and fosinopril is a combination medicine used to treat hypertension (high blood pressure).

Hydrochlorothiazide and fosinopril may also be used for purposes not listed in this medication guide.

Monopril-HCT (fosinopril sodium-hydrochlorothiazide tablets) is indicated for the treatment of hypertension.

These fixed dose combinations are not indicated for initial therapy. (See DOSAGE AND ADMINISTRATION.)

In using Monopril-HCT, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that fosinopril does not have a similar risk (see WARNINGS: Neutropenia/Agranulocytosis).

ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients (see WARNINGS: Head and Neck Angioedema and Intestinal Angioedema).

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.

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 infection.

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 disturbance, syncope.

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.

Neurologic/Psychiatric: Somnolence, depression, numbness/paresthesia.

Respiratory: Sinus congestion, pharyngitis, rhinitis.

Special Senses: Tinnitus.

Urogenital: Urinary tract infection, urinary frequency, dysuria.

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 and Mortality.

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.

Endocrine/Metabolic: Gout.

Gastrointestinal: Pancreatitis, hepatitis, dysphagia, abdominal distention, flatulence, appetite/weight change, dry mouth.

Hematologic: Lymphadenopathy.

Musculoskeletal: Arthralgia.

Neurologic/Psychiatric: Memory disturbance, tremor, confusion, mood change, sleep disturbance.

Respiratory: Bronchospasm, 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 photosensitivity.

Metabolic: Hyperglycemia, glycosuria, and hyperuricemia.

Musculoskeletal: Muscle spasm.

Neurologic: Vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness.

Applies to fosinopril / hydrochlorothiazide: oral tablet

General

The most common adverse reactions were cough, headache, upper respiratory infection, dizziness, weakness, musculoskeletal pain, pharyngitis, and fatigue.[Ref]

Respiratory

Common (1% to 10%): Cough, upper respiratory infection, pharyngitis, rhinitis, sinus abnormality, tracheobronchitis
Uncommon (0.1% to 1%): Congestion, dyspnea, epistaxis, sneezing
Frequency not reported: Sinus congestion

Fosinopril:
Common (1% to 10%): Cough, pharyngitis, rhinitis, upper respiratory infection
Uncommon (0.1% to 1%): Sinus abnormality, tracheobronchitis
Frequency not reported: Bronchospasm, laryngitis/hoarseness, epistaxis

Hydrochlorothiazide:
Frequency not reported: Respiratory distress, pneumonitis, pulmonary edema[Ref]

Gastrointestinal

Common (1% to 10%): Dyspepsia/heartburn, gastroenteritis, nausea/vomiting, epigastric pain
Uncommon (0.1% to 1%): Abnormal stool, constipation, diarrhea, abdominal distention, dry mouth, gastritis, oral lesion, intestinal obstruction, abdominal pain, eructation, halitosis
Frequency not reported: Esophagitis

Fosinopril:
Common (1% to 10%): Dyspepsia/heartburn, gastroenteritis, nausea/vomiting, epigastric pain
Frequency not reported: Pancreatitis, dysphagia, abdominal distention, flatulence, dry mouth

Hydrochlorothiazide:
Frequency not reported: Pancreatitis, sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness, vertigo
Uncommon (0.1% to 1%): Syncope, neuropathy entrapment, memory impairment, numbness, somnolence, paresthesia
Frequency not reported: Tinnitus

Fosinopril:
Common (1% to 10%): Dizziness, headache
Frequency not reported: Cerebrovascular accident, memory disturbance, tremor, taste disturbance

Hydrochlorothiazide:
Frequency not reported: Vertigo, lightheadedness, headache, paresthesia[Ref]

Genitourinary

Common (1% to 10%): Sexual dysfunction, urinary tract infection
Uncommon (0.1% to 1%): Menstrual disorder, urination abnormality, prostate disorder, vaginal bleeding
Frequency not reported: Urinary frequency, dysuria

Fosinopril:
Uncommon (0.1% to 1%): Sexual dysfunction, urinary tract infection

Hydrochlorothiazide:
Frequency not reported: Glycosuria[Ref]

Immunologic

Common (1% to 10%): Viral infection, influenza
Uncommon (0.1% to 1%): Allergy

Fosinopril:
Common (1% to 10%): Viral infection, influenza

Hydrochlorothiazide:
Frequency not reported: Anaphylactic reactions[Ref]

Other

Common (1% to 10%): Fatigue, weakness
Uncommon (0.1% to 1%): Edema, breast disorder, chest pain, chills, fever, cold sensation, malaise, extremity swelling, ear abnormality, ear infection, hearing abnormality
Frequency not reported: Breast mass, edema lower extremity

Fosinopril:
Common (1% to 10%): Fatigue, weakness

Hydrochlorothiazide:
Frequency not reported: Weakness[Ref]

Musculoskeletal

Common (1% to 10%): Musculoskeletal pain
Uncommon (0.1% to 1%): Limitation of movement, muscle cramp, musculoskeletal trauma, musculoskeletal chest pain, tendonitis, extremity weakness
Frequency not reported: Myalgia

Fosinopril:
Common (1% to 10%): Musculoskeletal pain
Frequency not reported: Arthralgia

Hydrochlorothiazide:
Frequency not reported: Muscle spasm[Ref]

Cardiovascular

Common (1% to 10%): Orthostatic hypotension
Uncommon (0.1% to 1%): Rhythm disturbance, flushing, hypertension, non-angina cardiac chest pain, hot flashes

Fosinopril:
Frequency not reported: Angina, myocardial infarction, hypertensive crisis, hypotension, claudication

Hydrochlorothiazide:
Frequency not reported: Orthostatic hypotension, necrotizing angiitis[Ref]

Dermatologic

Uncommon (0.1% to 1%): Acne, dermatitis, ecchymosis, extremity erythema, bacterial skin infection, pruritus, rash, skin discomfort, hyperhidrosis, angioedema

Fosinopril:
Frequency not reported: Urticaria, photosensitivity

Hydrochlorothiazide:
Frequency not reported: Stevens-Johnson syndrome, purpura, urticaria, rash, photosensitivity[Ref]

Psychiatric

Uncommon (0.1% to 1%): Libido change, depression, emotional lability/disturbance, insomnia

Fosinopril:
Frequency not reported: Confusion, mood change, sleep disturbance

Hydrochlorothiazide:
Frequency not reported: Restlessness[Ref]

Metabolic

Uncommon (0.1% to 1%): Polydipsia, appetite decreased, appetite increased, weight loss

Fosinopril:
Frequency not reported: Gout, appetite/weight change

Hydrochlorothiazide:
Frequency not reported: Anorexia, hyperglycemia, hyperuricemia[Ref]

Hepatic

Uncommon (0.1% to 1%): Hepatitis

Fosinopril:
Frequency not reported: Hepatitis, transaminases elevated, lactate dehydrogenase elevated, alkaline phosphatase elevated, serum bilirubin elevated

Hydrochlorothiazide:
Frequency not reported: Intrahepatic cholestatic jaundice[Ref]

Hematologic

Frequency not reported: Neutropenia, hematocrit decreased, hemoglobin decreased, eosinophilia

Fosinopril:
Frequency not reported: Lymphadenopathy, eosinophilia, hemoglobin decreased, leukopenia

Hydrochlorothiazide:
Frequency not reported: Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, hemolytic anemia[Ref]

Renal

Frequency not reported: BUN elevated, creatinine elevated

Fosinopril:
Frequency not reported: Renal insufficiency, BUN elevated, creatinine elevated[Ref]

Ocular

Fosinopril:
Frequency not reported: Vision disturbance, eye irritation

Hydrochlorothiazide:
Frequency not reported: Transient blurred vision, xanthopsia[Ref]

Some side effects of Monopril HCT may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.