Fosinopril; Hydrochlorothiazide

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Fosinopril; Hydrochlorothiazide uses


INDICATIONS AND USAGE

Fosinopril; Hydrochlorothiazide tablets are indicated for the treatment of hypertension.

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

In using Fosinopril; Hydrochlorothiazide tablets, 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 ).

CONTRAINDICATIONS

Fosinopril; Hydrochlorothiazide is contraindicated in patients who are anuric. Fosinopril; Hydrochlorothiazide is also contraindicated in patients who are hypersensitive to fosinopril, to any other ACE inhibitor, to hydrochlorothiazide, or other sulfonamide-derived drugs, or any other ingredient or component in the formulation. Hypersensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma.

WARNINGS

Anaphylactoid and Possibly Related Reactions

Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors may be subject to a variety of adverse reactions, some of them serious.

Head and Neck Angioedema

Angioedema of the face, extremities, lips, tongue, glottis and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with Fosinopril; Hydrochlorothiazide should be discontinued and appropriate therapy instituted immediately. When involvement of the tongue, glottis, or larynx appears likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine injection 1:1000 (0.3 mL to 0.5 mL) should be promptly administered (see PRECAUTIONS and ADVERSE REACTIONS ).

Intestinal Angioedema

Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain ; in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Anaphylactoid Reactions During Desensitization

Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.

Anaphylactoid Reactions During Membrane Exposure

Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Hypotension

Fosinopril; Hydrochlorothiazide can cause symptomatic hypotension. Like other ACE inhibitors, fosinopril has been only rarely associated with hypotension in uncomplicated hypertensive patients. Symptomatic hypotension is most likely to occur in patients who have been volume- and/or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume and/or salt depletion should be corrected before initiating therapy with Fosinopril; Hydrochlorothiazide.

Fosinopril; Hydrochlorothiazide should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of Fosinopril; Hydrochlorothiazide may potentiate the action of other antihypertensive drugs, especially ganglionic or peripheral adrenergic-blocking drugs. The antihypertensive effects of the thiazide component may also be enhanced in the post-sympathectomy patient.

In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria, azotemia, and with acute renal failure and death. In such patients, Fosinopril; Hydrochlorothiazide therapy should be started under close medical supervision; they should be followed closely for the first 2 weeks of treatment and whenever the dose of fosinopril or diuretic is increased.

If hypotension occurs, the patient should be placed in a supine position and, if necessary, treated with intravenous infusion of physiological saline. Fosinopril; Hydrochlorothiazide treatment usually can be continued following restoration of blood pressure and volume.

Impaired Renal Function

Fosinopril; Hydrochlorothiazide should be used with caution in patients with severe renal disease. Thiazides may precipitate azotemia in such patients, and the effects of repeated dosing may be cumulative.

When the renin-angiotensin-aldosterone system is inhibited by ACE inhibitors, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure, whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors (including fosinopril) may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death.

In some studies of hypertensive patients with unilateral or bilateral renal artery stenosis, treatment with ACE inhibitors has been associated with increases in blood urea nitrogen and serum creatinine; these increases were reversible upon discontinuation of ACE inhibitor therapy, concomitant diuretic therapy, or both. When such patients are treated with Fosinopril; Hydrochlorothiazide, renal function should be monitored during the first few weeks of therapy.

Some ACE-inhibitor-treated hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when the ACE inhibitor has been given concomitantly with a diuretic. Dosage reduction of Fosinopril; Hydrochlorothiazide may be required. Evaluation of the hypertensive patient should always include assessment of renal function (see DOSAGE AND ADMINISTRATION ).

Neutropenia/Agranulocytosis

Another angiotensin-converting enzyme inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression, rarely in uncomplicated patients, but more frequently (incidence possibly as great as once per 1,000 exposures) in patients with renal impairment, especially those who also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma. Available data from clinical trials of fosinopril are insufficient to show that fosinopril does not cause agranulocytosis at similar rates. Monitoring of white blood cell counts should be considered in patients with collagen-vascular disease, especially if the disease is associated with impaired renal function.

Neutropenia/agranulocytosis has also been associated with thiazide diuretics.

Fetal Toxicity

Pregnancy Category D

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue fosinopril and hydrochlorothiazide as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue fosinopril and hydrochlorothiazide, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to fosinopril and hydrochlorothiazide for hypotension, oliguria, and hyperkalemia.

Intrauterine exposure to thiazide diuretics is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that occurred in adults.

No teratogenic effects of fosinopril were seen in studies of pregnant rats and rabbits. On a mg/kg basis, the doses used were up to 180 times (in rats) and one time (in rabbits) the maximum recommended human dose. No teratogenic effects of fosinopril and hydrochlorothiazide were seen in studies of pregnant rats and rabbits. On a mg/kg (fosinopril and hydrochlorothiazide) basis, the doses used were up to 188/94 times (in rats) and 0.6/0.3 times (in rabbits) the maximum recommended human dose.

Impaired Hepatic Function

Rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. A patient receiving Fosinopril; Hydrochlorothiazide who develops jaundice or marked elevation of hepatic enzymes should discontinue Fosinopril; Hydrochlorothiazide tablets and receive appropriate medical follow-up.

Fosinopril; Hydrochlorothiazide should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Also, since the metabolism of fosinopril to fosinoprilat is normally dependent upon hepatic esterases, patients with impaired liver function could develop elevated plasma levels of fosinopril. In a study of patients with alcoholic or biliary cirrhosis the rate (but not the extent) of hydrolysis to fosinoprilat was reduced. In these patients the clearance of fosinoprilat was reduced, and the area under the fosinoprilat-time curve was approximately doubled.

Systemic Lupus Erythematosus

Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

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PRECAUTIONS

General

Derangements of Serum Electrolytes

In clinical trials of fosinopril monotherapy, hyperkalemia occurred in approximately 2.6% of hypertensive patients receiving fosinopril. In most cases, these were isolated values which resolved despite continued therapy. Risk factors for the development of hyperkalemia included renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes.

Conversely, treatment with thiazide diuretics has been associated with hypokalemia, hyponatremia, and hypochloremic alkalosis. These disturbances have sometimes been manifest as one or more of dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, nausea, and vomiting. Hypokalemia can also sensitize or exaggerate the response of the heart to the toxic effects of digitalis. The risk of hypokalemia is greatest in patients with cirrhosis of the liver, in patients experiencing a brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes, and in patients receiving concomitant therapy with corticosteroids or ACTH.

The opposite effects of fosinopril and hydrochlorothiazide on serum potassium will approximately balance each other in many patients, so that no net effect upon serum potassium will be seen. In other patients, one or the other effect may be dominant. Initial and periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

Chloride deficits are generally mild and require specific treatment only under extraordinary circumstances (e.g., in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients; appropriate therapy is water restriction rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Calcium excretion is decreased by thiazides. In a few patients on prolonged thiazide therapy, pathological changes in the parathyroid gland have been observed, with hypercalcemia and hypophosphatemia. More serious complications of hyperparathyroidism (renal lithiasis, bone resorption, and peptic ulceration) have not been seen.

Thiazides increase the urinary excretion of magnesium, and hypomagnesemia may result.

Other Metabolic Disturbances

Thiazide diuretics tend to reduce glucose tolerance and to raise serum levels of cholesterol, triglycerides, and uric acid. These effects are usually minor, but frank gout or overt diabetes may be precipitated in susceptible patients.

Cough

Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.

Surgery/Anesthesia

In patients undergoing surgery or during anesthesia with agents that produce hypotension, fosinopril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.

Information for Patients

Angioedema

Angioedema, including laryngeal edema, can occur with treatment with ACE inhibitors, especially following the first dose. A patient receiving Fosinopril; Hydrochlorothiazide should be told to report immediately any signs or symptoms suggesting angioedema and to take no more drug until after consulting with the prescribing physician.

Pregnancy

Female patients of childbearing age should be told about the consequences of exposure to fosinopril and hydrochlorothiazide during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

Symptomatic Hypotension

A patient receiving Fosinopril; Hydrochlorothiazide tablets should be cautioned that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to the prescribing physician. The patients should be told that if syncope occurs, Fosinopril; Hydrochlorothiazide should be discontinued until the physician has been consulted.

All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.

Hyperkalemia

A patient receiving Fosinopril; Hydrochlorothiazide should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.

Neutropenia

Patients should be told to promptly report any indication of infection, which could be a sign of neutropenia.

Laboratory Tests

Therapy with Fosinopril; Hydrochlorothiazide should be interrupted for a few days before carrying out tests of parathyroid function.

Fosinopril may cause false low measurement of serum digoxin levels when the Digi-Tab® (Nuclear Medical) RIA Kit is used. The accuracy of the Coat-A-Count® (Diagnostic Products Corporation) kit is not affected.

Drug Interactions

Dual Blockade of the Renin-Angiotensin System

Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on fosinopril and hydrochlorothiazide and other agents that affect the RAS.

Do not co-administer aliskiren with fosinopril and hydrochlorothiazide in patients with diabetes. Avoid use of aliskiren with fosinopril and hydrochlorothiazide in patients with renal impairment (GFR less than 60 mL/min).

Potassium Supplements and Potassium-Sparing Diuretics

As noted above, the net effect of Fosinopril; Hydrochlorothiazide may be to elevate a patient's serum potassium, to reduce it, or to leave it unchanged. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia. If concomitant use of such agents is indicated, they should be given with caution, and the patient's serum potassium should be monitored frequently.

Lithium

Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. Because renal clearance of lithium is reduced by thiazides, the risk of lithium toxicity is presumably raised further when, as in therapy with Fosinopril; Hydrochlorothiazide tablets, a thiazide diuretic is co-administered with the ACE inhibitor. Fosinopril sodium-hydrochlorothiazide and lithium should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended.

Antacids

In a clinical pharmacology study, serum levels and urinary excretion of fosinoprilat were reduced when fosinopril was co-administered with an antacid suggesting that antacids may impair absorption of fosinopril. If concomitant administration of these agents is indicated, dosing should be separated by 2 hours.

Gold

Nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including Fosinopril; Hydrochlorothiazide.

Other

The bioavailability of unbound fosinoprilat is not altered by coadministration of fosinopril with aspirin, chlorthalidone, cimetidine, digoxin, metoclopramide, nifedipine, propranolol, propantheline, or warfarin. Other ACE inhibitors have had less than additive effects with beta- adrenergic blockers, presumably because drugs of both classes lower blood pressure by inhibiting parts of the renin-angiotensin system.

Interaction studies with warfarin have failed to identify any clinically important effects of fosinopril on the serum concentration or clinical effects of the anticoagulant.

Insulin requirements in diabetic patients may be increased, decreased, or unchanged.

Thiazides may decrease arterial responsiveness to norepinephrine, but not enough to preclude effectiveness of the pressor agent for therapeutic use.

Thiazides may increase the responsiveness to tubocurarine.

The diuretic, natriuretic, and antihypertensive effects of thiazide diuretics may be reduced by concurrent administration of nonsteroidal anti-inflammatory agents; the effects of these agents on the antihypertensive effect of Fosinopril; Hydrochlorothiazide have not been studied.

By alkalinizing the urine, hydrochlorothiazide may decrease the effectiveness of methenamine.

Cholestyramine and Colestipol Resins

Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Fosinopril and Hydrochlorothiazide

Reproductive studies and long-term carcinogenicity studies with Fosinopril; Hydrochlorothiazide has not been conducted. The combination of fosinopril and hydrochlorothiazide was not mutagenic in the Ames microbial mutagen test, the mouse lymphoma forward mutation assay, or the Chinese hamster ovary cell cytogenetic assay. The combination was also not genotoxic in a mouse micronucleus test in vivo.

Fosinopril; Hydrochlorothiazide

No evidence of a carcinogenicity was found when fosinopril was given in the diet to rats and mice for up to 24 months at doses up to 400 mg/kg/day. On a body-weight basis, the highest dose was about 250 times the maximum human dose of 80 mg, given to a 50 kg subject. On a body-surface-area basis, this dose is 20 to 40 (rats) times the maximum human dose.

Neither fosinopril nor the fosinoprilat moiety was mutagenic in the Ames microbial mutagen test, the mouse lymphoma forward mutation assay, or a mitotic gene conversion assay. Fosinopril was also not genotoxic in a mouse micronucleus test in vivo and a mouse bone marrow cytogenetic assay in vivo.

In Chinese hamster ovary cell cytogenetic assay, fosinopril increased the frequency of chromosomal aberrations when tested without metabolic activation at a concentration that was toxic to the cells. However, there was no increase in chromosomal aberrations at lower drug concentrations without metabolic activation or at any concentration with metabolic activation.

There were no adverse reproductive effects in male and female rats treated with up to 60 mg/kg daily. At doses 4 times higher, slight increases in pairing time were seen. This higher dose is about 125 (body-surface-area basis) or 600 (body-weight basis) times greater than the dose received by a 50 kg human receiving 20 mg a day.

Hydrochlorothiazide

Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide for two years at doses up to 100 (rats) and 600 (mice) mg/kg/day. On a body weight basis, these highest doses were about 2,400 times (mice) or 400 times (rats) the Fosinopril; Hydrochlorothiazide dose of 12.5 mg, given to a 50 kg subject. On a body surface area basis, these doses are 226 times (mice) and 82 times (rats) the fosinopril sodium-hydrochlorothiazide dose. These studies uncovered no evidence of carcinogenicity in rats or female mice, but there was equivocal evidence of hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA 98, TA 100, TA 1535,TA 1537, and TA 1538 of Salmonella typhimurium (Ames assay); in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations; or in in vivo assays using mouse germinal cell chromosomes; Chinese Hamster bone-marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Using concentrations of hydrochlorothiazide of 43 mg/mL to 1300 mg/mL, positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the Mouse Lymphoma Cell (mutagenicity) assays. Using an unspecified concentration of hydrochlorothiazide, positive test results were also obtained in the Aspergillus nidulans nondisjunction assay.

No adverse effects upon fertility were seen when rats and mice received dietary hydrochlorothiazide prior to mating and throughout gestation at doses up to 4 (rats) and 100 (mice) mg/kg/day. These doses are from 3.2 (body surface area basis in rats) to 400 (weight basis in mice) times greater than the dose received by a 50 kg human receiving 12.5 mg a day.

Pregnancy

Nursing Mothers

Both fosinopril and hydrochlorothiazide are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue fosinopril sodium-hydrochlorothiazide, taking into account the importance of the drug to the mother.

Geriatric Use

Clinical studies of Fosinopril; Hydrochlorothiazide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Pediatric Use

Neonates with a history of in utero exposure to fosinopril and hydrochlorothiazide:

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Removal of fosinopril and hydrochlorothiazide, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these means.

Safety and effectiveness in pediatric patients have not been established.

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ADVERSE REACTIONS

Fosinopril; Hydrochlorothiazide tablets have 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 Fosinopril; Hydrochlorothiazide, 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 Fosinopril; Hydrochlorothiazide treated patients.

The most common reasons for discontinuation of therapy with fosinopril sodium-hydrochlorothiazide in U.S. studies were headache, 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 Fosinopril; Hydrochlorothiazide is shown in the table below.


Fosinopril; Hydrochlorothiazide and

Hydrochlorothiazide

(N=660)

%


Placebo

(N=368)

%


Headache


7


12.8


Cough


5.6


1.1


Fatigue


3.9


2.4


Dizziness


3.2


2.2


Upper Respiratory Infection


2.3


2.7


Musculoskeletal Pain


2


1.9


Other side effects considered possibly or probably related to study drug that occurred in controlled trials in 0.5% to less than 2% of patients treated with Fosinopril; Hydrochlorothiazide, 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 Fosinopril; Hydrochlorothiazide 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.

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 Fosinopril; Hydrochlorothiazide; 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.

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OVERDOSAGE

To obtain up-to-date information about the treatment of overdose, a good resource is a certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and unusual drug kinetics in your patient.

No specific information is available on the treatment of overdosage with Fosinopril; Hydrochlorothiazide tablets; treatment should be symptomatic and supportive. Therapy with Fosinopril; Hydrochlorothiazide should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance, and hypotension should be treated by established procedures.

In rats, single oral doses of 2600 mg/kg of fosinopril were associated with significant lethality. In single-dose studies of hydrochlorothiazide, most rats survived doses of up to 2750 mg/kg. Both doses are more than 6000 times (on a mg/kg basis) the maximum recommended daily dose of either fosinopril or hydrochlorothiazide in Fosinopril; Hydrochlorothiazide.

Data from human overdoses of fosinopril are scanty, but the most common manifestation of human fosinopril overdosage is likely to be hypotension. In human hydrochlorothiazide overdose, the most common signs and symptoms observed have been those of dehydration and electrolyte depletion (hypokalemia, hypochloremia, hyponatremia). If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.

Laboratory determinations of serum levels of fosinopril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of fosinopril overdose. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of fosinopril and its metabolites. Fosinoprilat is poorly removed from the body by hemodialysis or peritoneal dialysis.

Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of fosinopril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of fosinopril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat fosinopril overdose by infusion of normal saline solution.

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DOSAGE AND ADMINISTRATION

Fosinopril is an effective treatment of hypertension in once-daily doses of 10 mg to 80 mg, while hydrochlorothiazide is effective in doses of 12.5 mg to 50 mg per day. In clinical trials of fosinopril/hydrochlorothiazide combination therapy using fosinopril doses of 2.5 mg to 40 mg and hydrochlorothiazide doses at 5 mg to 37.5 mg, the antihypertensive effects increased with increasing dose of either component.

The hazards of fosinopril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of fosinopril and hydrochlorothiazide will be associated with both sets of dose-independent hazards. To minimize dose-independent hazards, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Dose Titration by Clinical Effect

A patient whose blood pressure is not adequately controlled with fosinopril or hydrochlorothiazide monotherapy may be switched to combination therapy with fosinopril sodium-hydrochlorothiazide tablets. Dosage must be guided by clinical response; controlled clinical trials showed that the addition of 12.5 mg of hydrochlorothiazide to 10 mg to 20 mg of fosinopril will typically be associated with additional reduction in seated diastolic blood pressure at 24 hours after dosing. On average, the effect of the combination of 10 mg of fosinopril with 12.5 mg of hydrochlorothiazide was similar to the effect seen with monotherapy using either 40 mg of fosinopril or 37.5 mg of hydrochlorothiazide.

Use in Renal Impairment

In patients with severe renal impairment (creatinine clearance is less than 30 mL/min/1.73m2, serum creatine roughly greater than or equal to 3 mg/dL or 265 mcmol/L), loop diuretics are preferred to thiazides, so Fosinopril; Hydrochlorothiazide tablets are not recommended. In patients with lesser degrees of renal impairment, Fosinopril; Hydrochlorothiazide tablets may be used with no change in dosage.

HOW SUPPLIED

Fosinopril; Hydrochlorothiazide Tablets, for oral administration, are available as

10 mg/12.5 mg

Light pink, round, debossed with “E” over “341” on one side and plain on the other side and supplied as:

NDC 0185-0341-01 bottles of 100

NDC 0185-0341-10 bottles of 1000

20 mg/12.5 mg

Dark pink, round, debossed with “E” over “342” on one side and scored on the other side and supplied as:

NDC 0185-0342-01 bottles of 100

NDC 0185-0342-10 bottles of 1000

Store at 20° to 25°C (68° to 77°F). Protect from moisture by keeping bottle tightly closed.

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Distributed by

Sandoz Inc.

Princeton, NJ 08540

OS8219

Rev. April 2016

MF0341REV04/16

NDC 0185-0341-01

Fosinopril; Hydrochlorothiazide Tablets

10 mg/12.5 mg

Rx only

100 Tablets

Sandoz

10 mg/12.5 mg x 100 Tablets

NDC 0185-0342-01

Fosinopril; Hydrochlorothiazide Tablets

20 mg/12.5 mg

Rx only

100 Tablets

Sandoz

20 mg/12.5 mg x 100 Tablets

Fosinopril; Hydrochlorothiazide pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Fosinopril; Hydrochlorothiazide available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Fosinopril; Hydrochlorothiazide destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Fosinopril; Hydrochlorothiazide Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Fosinopril; Hydrochlorothiazide pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."HYDROCHLOROTHIAZIDE TABLET [QUALITEST PHARMACEUTICALS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."FOSINOPRIL SODIUM TABLET [EON LABS, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."AMLODIPINE BESYLATE; HYDROCHLOROTHIAZIDE; OLMESARTAN MEDOXOMIL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Fosinopril; Hydrochlorothiazide?

Depending on the reaction of the Fosinopril; Hydrochlorothiazide after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Fosinopril; Hydrochlorothiazide not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Fosinopril; Hydrochlorothiazide addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Fosinopril; Hydrochlorothiazide, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Fosinopril; Hydrochlorothiazide consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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