Fosinopril Sodium and Hydrochlorothiazide
Tablet · Oral
Uses
Fosinopril sodium and 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 sodium and hydrochlorothiazide, 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 ).
Dosage and administration
Fosinopril is an effective treatment of hypertension in once-daily doses of 10 to 80 mg, while hydrochlorothiazide is effective in doses of 12.5 to 50 mg per day. In clinical trials of fosinopril/hydrochlorothiazide combination therapy using fosinopril doses of 2.5 to 40 mg and hydrochlorothiazide doses at 5 to 37.5 mg, the antihypertensive effects increased with increasing dose of either component. The hazards (see WARNINGS ) 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 and hydrochlorothiazide tablets. Dosage must be guided by clinical response; controlled clinical trials showed that the addition of 12.5 mg of hydrochlorothiazide to 10 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 <30 mL/min/1.73 m 2 , serum creatine roughly ≥3 mg/dL or 265 µmol/L), loop diuretics are preferred to thiazides, so fosinopril sodium and hydrochlorothiazide tablets are not recommended. In patients with lesser degrees of renal impairment, fosinopril sodium and hydrochlorothiazide tablets may be used with no change in dosage.
Contraindications
Fosinopril sodium and hydrochlorothiazide tablets are contraindicated in patients who are anuric. Fosinopril sodium and 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 (including fosinopril sodium and hydrochlorothiazide) 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 sodium and 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 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 (with or without nausea or vomiting); 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 sodium and 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 sodium and hydrochlorothiazide. Fosinopril sodium and hydrochlorothiazide tablets should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of fosinopril sodium and 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 (rarely) with acute renal failure and death. In such patients, fosinopril sodium and 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 sodium and hydrochlorothiazide treatment usually can be continued following restoration of blood pressure and volume. Impaired Renal Function Fosinopril sodium and 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 sodium and hydrochlorothiazide, renal function should be monitored during the first few weeks of therapy. Some ACE-inhibitor-treated hypertensive patients with no apparent preexisting 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 sodium and hydrochlorothiazide may be required. Evaluation of the hypertensive patient should always include assessment of renal function (see DOSAGE AND ADMINISTRATION ).
Precautions
General Derangements of Serum Electrolytes In clinical trials of fosinopril monotherapy, hyperkalemia (serum potassium at least 10% greater than the upper limit of normal) 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 sodium and hydrochlorothiazide should be told to report immediately any signs or symptoms suggesting angioedema (swelling of face, eyes, lips, or tongue, or difficulty in breathing) 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 sodium and 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 sodium and 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 sodium and 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 (e.g., sore throat, fever), which could be a sign of neutropenia. Non-melanoma Skin Cancer: Instruct patients taking hydrochlorothiazide to protect skin from the sun and undergo regular skin cancer screening. Laboratory Tests Therapy with fosinopril sodium and 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 Potassium supplements and potassium-sparing diuretics As noted above (“Derangements of Serum Electrolytes”), the net effect of fosinopril sodium and hydrochlorothiazide may be to elevate a patient’s serum potassium, to reduce it, or to leave it unchanged.
Side effects
Fosinopril sodium and 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 sodium and 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 sodium and hydrochlorothiazide-treated patients. The most common reasons for discontinuation of therapy with fosinopril sodium and hydrochlorothiazide 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 fosinopril sodium and hydrochlorothiazide are shown in the table below. Reactions Possibly or Probably Drug-Related (Incidence in Placebo-Controlled Studies) Fosinopril Sodium 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 <2% of patients treated with fosinopril sodium and 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 sodium and 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 sodium and 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.
Drug interactions
Drug Interactions Potassium supplements and potassium-sparing diuretics As noted above (“Derangements of Serum Electrolytes”), the net effect of fosinopril sodium and 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 sodium and hydrochlorothiazide tablets, a thiazide diuretic is coadministered with the ACE inhibitor. Fosinopril sodium and 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 coadministered with an antacid (aluminum hydroxide, magnesium hydroxide, and simethicone) 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 sodium and 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 (if any) of these agents on the antihypertensive effect of fosinopril sodium and 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. Dual Blockade of the Renin-Angiotensin System (RAS) 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 <60 mL/min).
Pediatric use
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.
Geriatric use
Geriatric Use Clinical studies of fosinopril sodium and 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.
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 sodium and hydrochlorothiazide tablets; treatment should be symptomatic and supportive. Therapy with fosinopril sodium and 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 sodium and 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.
Description
Fosinopril sodium, USP is a white to almost white 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 molecular formula is C 30 H 45 NNaO 7 P, 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-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; its structural formula is: Its molecular formula is C 7 H 8 ClN 3 O 4 S 2 , and its molecular weight is 297.73. Hydrochlorothiazide is a thiazide diuretic. Fosinopril sodium and hydrochlorothiazide tablets, USP are a combination of fosinopril sodium, USP and hydrochlorothiazide, USP. They are available for oral use in two tablet strengths: fosinopril sodium and hydrochlorothiazide tablets, USP 10 mg/12.5 mg, containing 10 mg of fosinopril sodium, USP and 12.5 mg of hydrochlorothiazide, USP; and fosinopril sodium and hydrochlorothiazide tablets, USP 20 mg/12.5 mg, containing 20 mg of fosinopril sodium, USP and 12.5 mg of hydrochlorothiazide, USP. The inactive ingredients of the tablets include lactose anhydrous, ferric oxide red, ferric oxide yellow, croscarmellose sodium, povidone, isopropyl alcohol, glyceryl distearate, and sodium lauryl sulfate. Fosinopril Sodium Chemical Structure Hydrochlorothiazide Chemical Structure
How supplied
Fosinopril Sodium and Hydrochlorothiazide Tablets USP, 10 mg/12.5 mg are peach colored, round biconvex, uncoated tablets debossed with ‘C 84’ on one side and plain on the other side. Bottle of 30 NDC 65862-308-30 Bottle of 100 NDC 65862-308-01 Bottle of 1,000 NDC 65862-308-99 Fosinopril Sodium and Hydrochlorothiazide Tablets USP, 20 mg/12.5 mg are peach colored, round biconvex, uncoated tablets debossed with ‘C 85’ on one side and “deep score line” on the other side. Bottle of 30 NDC 65862-309-30 Bottle of 100 NDC 65862-309-01 Bottle of 1,000 NDC 65862-309-99 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from moisture by keeping bottle tightly closed. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Revised: 01/2022
Patient information
Information for Patients Angioedema Angioedema, including laryngeal edema, can occur with treatment with ACE inhibitors, especially following the first dose. A patient receiving fosinopril sodium and hydrochlorothiazide should be told to report immediately any signs or symptoms suggesting angioedema (swelling of face, eyes, lips, or tongue, or difficulty in breathing) 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 sodium and 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 sodium and 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 sodium and 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 (e.g., sore throat, fever), which could be a sign of neutropenia.
Label text from the FDA structured product label by Aurobindo Pharma Limited (revised Apr 28, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Fosinopril Sodium in 4 products
- Hydrochlorothiazide in 4 products
Fosinopril Sodium and Hydrochlorothiazide NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 65862-308 | Fosinopril Sodium 10 mg/1; Hydrochlorothiazide 12.5 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 65862-309 | Fosinopril Sodium 20 mg/1; Hydrochlorothiazide 12.5 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 69097-972 | Fosinopril Sodium 10 mg/1; Hydrochlorothiazide 12.5 mg/1 Tablet | CIPLA USA INC. | ANDA |
| 69097-973 | Fosinopril Sodium 20 mg/1; Hydrochlorothiazide 12.5 mg/1 Tablet | CIPLA USA INC. | ANDA |
Frequently asked questions
What is Fosinopril Sodium and Hydrochlorothiazide used for?
Fosinopril sodium and 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 sodium and hydrochlorothiazide, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis,…
What are the side effects of Fosinopril Sodium and Hydrochlorothiazide?
Fosinopril sodium and 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… See the full label for the complete list.
Who makes Fosinopril Sodium and Hydrochlorothiazide?
Fosinopril Sodium and Hydrochlorothiazide is listed by 2 labelers in the FDA NDC directory, including Aurobindo Pharma Limited, CIPLA USA INC..