Fosinopril sodium/Hydrochlorothiazide

Description

Fosinopril sodium, USP is a white to off-white powder that is freely soluble in methanol and soluble in chloroform and water. It is chemically designated as L-proline, 4-cyclohexyl-1-[[2-methyl-1-(1-oxopropoxy)-propoxy-(4-phenylbutyl)-phosphinyl]acetyl]-, sodium salt, trans-, with a molecular formula of C30H45NNaO7P and a molecular weight of 585.65. The active metabolite, fosinoprilat, functions as a non-sulfhydryl angiotensin-converting enzyme inhibitor, formed through hepatic cleavage of the ester group.

Hydrochlorothiazide, USP is a white or practically white, odorless crystalline powder, slightly soluble in water, freely soluble in sodium hydroxide solution, n-butylamine, and dimethylformamide, sparingly soluble in methanol, and insoluble in ether, chloroform, and dilute mineral acids. It is chemically identified as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, with a molecular formula of C7H8ClN3O4S2 and a molecular weight of 297.73. Hydrochlorothiazide is classified as a thiazide diuretic.

Fosinopril sodium and hydrochlorothiazide tablets, USP combine fosinopril sodium, USP and hydrochlorothiazide, USP for oral administration. The tablets are available in two strengths: 10 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide (10/12.5) and 20 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide (20/12.5). Inactive ingredients include anhydrous lactose, colloidal silicon dioxide, crospovidone, microcrystalline cellulose, povidone, and talc.

Uses and Indications

Fosinopril sodium and hydrochlorothiazide tablets, USP are indicated for the treatment of hypertension in patients requiring combination therapy.

Limitations of Use: This fixed-dose combination is not indicated for initial therapy in the management of hypertension.

Dosage and Administration

Fosinopril is indicated for the treatment of hypertension and is administered in once-daily doses ranging from 10 mg to 80 mg. Hydrochlorothiazide is effective in daily doses of 12.5 mg to 50 mg.

For patients requiring combination therapy, clinical trials have demonstrated the efficacy of fosinopril doses between 2.5 mg and 40 mg, alongside hydrochlorothiazide doses ranging from 5 mg to 37.5 mg. When a patient's blood pressure is not adequately controlled with monotherapy using either fosinopril or hydrochlorothiazide, a switch to fosinopril sodium and hydrochlorothiazide tablets, USP, may be considered.

Dosage adjustments should be guided by the clinical response of the patient. The addition of 12.5 mg of hydrochlorothiazide to a regimen of 10 mg to 20 mg of fosinopril typically results in an additional reduction in seated diastolic blood pressure observed 24 hours post-dosing. Notably, the combination of 10 mg of fosinopril with 12.5 mg of hydrochlorothiazide has shown effects comparable to monotherapy with either 40 mg of fosinopril or 37.5 mg of hydrochlorothiazide.

In patients with severe renal impairment, defined as a creatinine clearance of less than 30 mL/min/1.73 m² or a serum creatinine level of approximately 3 mg/dL (265 µmol/L), the use of loop diuretics is preferred over thiazides; therefore, fosinopril sodium and hydrochlorothiazide tablets, USP, are not recommended in this population. For patients with lesser degrees of renal impairment, the combination may be used without necessitating a change in dosage.

Contraindications

Fosinopril sodium and hydrochlorothiazide is contraindicated in patients who are anuric. Additionally, it is contraindicated in individuals with a known hypersensitivity to fosinopril, any other ACE inhibitor, hydrochlorothiazide, sulfonamide-derived drugs, or any other component of the formulation. Hypersensitivity reactions may be more prevalent in patients with a history of allergy or bronchial asthma.

Warnings and Precautions

Patients receiving ACE inhibitors, including fosinopril sodium and hydrochlorothiazide, may experience a range of serious adverse reactions. Notably, anaphylactoid reactions, including angioedema, have been reported. Angioedema can affect various regions such as the face, extremities, lips, tongue, glottis, and larynx, with laryngeal edema posing a risk of fatality. In the event of laryngeal stridor or angioedema, it is imperative to discontinue treatment immediately and initiate appropriate therapy. Additionally, intestinal angioedema has been documented, presenting with abdominal pain, which resolved upon cessation of the ACE inhibitor. Life-threatening anaphylactoid reactions may also occur during desensitization treatment with hymenoptera venom in patients on ACE inhibitors, as well as in those undergoing dialysis with high-flux membranes.

Symptomatic hypotension is a potential risk associated with fosinopril sodium and hydrochlorothiazide, particularly in patients who are volume- and/or salt-depleted. Therefore, initiation of therapy should occur under close medical supervision in patients with congestive heart failure to mitigate the risk of excessive hypotension.

Caution is advised when administering these medications to patients with severe renal disease, as changes in renal function may be expected in susceptible individuals. Monitoring of renal function is recommended during the initial weeks of therapy, especially in patients with renal artery stenosis.

Patients with collagen-vascular disease, particularly those with impaired renal function, should have their white blood cell counts monitored due to the risk of neutropenia or agranulocytosis. Furthermore, in patients with impaired hepatic function, treatment should be approached with caution, and discontinuation is warranted if jaundice or significant elevation of hepatic enzymes occurs.

Thiazide diuretics, including hydrochlorothiazide, have been associated with exacerbation or activation of systemic lupus erythematosus, necessitating careful consideration in affected patients.

For laboratory testing, it is recommended that therapy with fosinopril sodium and hydrochlorothiazide be interrupted for several days prior to conducting tests of parathyroid function. Additionally, fosinopril may lead to falsely low serum digoxin measurements when using the Digi-Tab (Nuclear Medical) RIA Kit.

Emergency medical assistance should be sought if laryngeal stridor or angioedema of the face, tongue, or glottis occurs, necessitating immediate discontinuation of treatment and appropriate intervention. Patients should also discontinue the use of fosinopril sodium and hydrochlorothiazide and consult their healthcare provider if jaundice or marked elevation of hepatic enzymes is observed, ensuring proper medical follow-up.

Side Effects

Patients receiving treatment may experience a range of adverse reactions. The most common adverse reactions observed in placebo-controlled studies include headache (7% vs. 12.8% in placebo), cough (5.6% vs. 1.1% in placebo), fatigue (3.9% vs. 2.4% in placebo), dizziness (3.2% vs. 2.2% in placebo), upper respiratory infection (2.3% vs. 2.7% in placebo), and musculoskeletal pain (2% vs. 1.9% in placebo).

Other side effects occurring in 0.5% to less than 2% of patients include a variety of general, cardiovascular, dermatologic, endocrine/metabolic, gastrointestinal, immunologic, musculoskeletal, neurologic/psychiatric, respiratory, special senses, and urogenital reactions. General side effects may consist of chest pain, weakness, fever, and viral infection. Cardiovascular effects include orthostatic hypotension (1.8% in treated patients vs. 0.3% in placebo), edema, flushing, rhythm disturbances, and syncope. Dermatologic reactions may manifest as pruritus and rash, while endocrine/metabolic effects can include sexual dysfunction, changes in libido, and breast mass. Gastrointestinal side effects may involve nausea/vomiting, diarrhea, dyspepsia/heartburn, abdominal pain, and gastritis/esophagitis. Immunologic reactions such as angioedema, musculoskeletal issues like myalgia/muscle cramps, and neurologic/psychiatric effects including somnolence, depression, and numbness/paresthesia have also been reported. Respiratory side effects may include sinus congestion, pharyngitis, and rhinitis, while special senses may be affected by tinnitus. Urogenital reactions can involve urinary tract infections, urinary frequency, and dysuria. Laboratory test abnormalities may include changes in serum electrolytes, uric acid, glucose, magnesium, cholesterol, triglycerides, calcium, and neutropenia.

Serious adverse reactions have been reported, including head and neck angioedema, which can be fatal and may involve angioedema of the face, extremities, lips, tongue, glottis, and larynx. Intestinal angioedema may present as abdominal pain with or without nausea or vomiting. Anaphylactoid reactions can occur, particularly during desensitization or membrane exposure, and symptomatic hypotension may arise, especially in volume-depleted patients. Neutropenia and agranulocytosis have been noted, necessitating monitoring of white blood cell counts in patients with collagen-vascular disease.

Additional serious cardiovascular events such as angina, myocardial infarction, cerebrovascular accidents, hypertensive crises, hypotension, and claudication have been documented. Dermatologic reactions may include urticaria and photosensitivity, while endocrine/metabolic issues can involve gout. Gastrointestinal complications may consist of pancreatitis, hepatitis, dysphagia, abdominal distention, flatulence, appetite or weight changes, and dry mouth. Hematologic reactions such as lymphadenopathy, musculoskeletal complaints like arthralgia, and neurologic/psychiatric disturbances including memory issues, tremors, confusion, mood changes, and sleep disturbances have also been reported. Respiratory side effects may include bronchospasm, laryngitis/hoarseness, and epistaxis. Special senses may experience vision and taste disturbances, as well as eye irritation. Urogenital issues may lead to renal insufficiency, and laboratory test abnormalities may show elevations in BUN and creatinine, leukopenia, eosinophilia, and elevated liver function tests.

Drug Interactions

Dual blockade of the Renin-Angiotensin System (RAS) through the use of angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with an increased risk of hypotension, hyperkalemia, and alterations in renal function, including acute renal failure, compared to monotherapy. It is essential to closely monitor blood pressure, renal function, and electrolyte levels in patients receiving fosinopril and hydrochlorothiazide alongside other RAS-affecting agents.

Co-administration of aliskiren with fosinopril and hydrochlorothiazide is contraindicated in patients with diabetes and should be avoided in those with renal impairment (GFR <60 ml/min).

Pharmacodynamic Interactions

Potassium-sparing diuretics (such as spironolactone, amiloride, and triamterene) or potassium supplements may elevate the risk of hyperkalemia. If the use of these agents is necessary, they should be administered with caution, and serum potassium levels should be monitored frequently.

In patients receiving ACE inhibitors, including fosinopril, there is a risk of increased serum lithium levels and potential lithium toxicity when lithium is co-administered. The risk of lithium toxicity is further heightened when a thiazide diuretic, such as hydrochlorothiazide, is used concurrently. Therefore, caution is advised when co-administering fosinopril sodium, hydrochlorothiazide, and lithium, with frequent monitoring of serum lithium levels recommended.

Pharmacokinetic Interactions

The absorption of fosinopril may be impaired by antacids containing aluminum hydroxide, magnesium hydroxide, and simethicone, as evidenced by reduced serum levels and urinary excretion of fosinoprilat. If these antacids are to be used, dosing should be separated by at least 2 hours.

Nitritoid reactions, characterized by symptoms such as facial flushing, nausea, vomiting, and hypotension, have been reported infrequently in patients receiving injectable gold (sodium aurothiomalate) in conjunction with ACE inhibitors, including fosinopril sodium and hydrochlorothiazide.

The bioavailability of unbound fosinoprilat is not significantly affected by coadministration with aspirin, chlorthalidone, cimetidine, digoxin, metoclopramide, nifedipine, propranolol, propantheline, or warfarin. Interaction studies have not identified any clinically significant effects of fosinopril on the serum concentration or clinical effects of warfarin.

Thiazides may reduce arterial responsiveness to norepinephrine, although this does not impede the therapeutic effectiveness of norepinephrine as a pressor agent. Additionally, thiazides may enhance responsiveness to tubocurarine.

The diuretic, natriuretic, and antihypertensive effects of thiazide diuretics may be diminished by the concurrent use of nonsteroidal anti-inflammatory agents; however, the specific effects of these agents on the antihypertensive efficacy of fosinopril sodium and hydrochlorothiazide have not been thoroughly investigated.

Hydrochlorothiazide may decrease the effectiveness of methenamine by alkalinizing the urine. Furthermore, the absorption of hydrochlorothiazide can be significantly impaired in the presence of anionic exchange resins, with single doses of cholestyramine or colestipol resins binding hydrochlorothiazide and reducing its gastrointestinal absorption by up to 85% and 43%, respectively.

Packaging & NDC

The table below lists all NDC Code configurations of Fosinopril Sodium and Hydrochlorothiazide, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Pediatric patients, particularly neonates with a history of in utero exposure to fosinopril and hydrochlorothiazide, may experience complications such as oliguria or hypotension. In such cases, it is crucial to provide support for blood pressure and renal perfusion. Interventions such as exchange transfusions or dialysis may be necessary to address hypotension and/or substitute for impaired renal function. However, it is important to note that the removal of fosinopril and hydrochlorothiazide from the neonatal circulation is not significantly accelerated by these procedures.

The safety and effectiveness of fosinopril and hydrochlorothiazide in pediatric patients have not been established. Therefore, caution is advised when considering the use of this medication in children.

Geriatric Use

Clinical studies of fosinopril sodium and hydrochlorothiazide did not include a sufficient number of subjects aged 65 and over to determine whether these elderly patients respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly and younger patients.

In general, dose selection for geriatric patients should be approached with caution. It is recommended to start at the low end of the dosing range, taking into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies. Careful monitoring of these patients is advised to ensure safety and efficacy.

Pregnancy

The use of fosinopril and hydrochlorothiazide during pregnancy is classified as Pregnancy Category D. Administration of drugs that act on the renin-angiotensin system during the second and third trimesters is associated with significant risks, including reduced fetal renal function, increased fetal and neonatal morbidity, and mortality. Oligohydramnios resulting from such use can lead to fetal lung hypoplasia and skeletal deformations. Potential adverse neonatal outcomes include skull hypoplasia, anuria, hypotension, renal failure, and death. Therefore, it is imperative to discontinue fosinopril and hydrochlorothiazide as soon as pregnancy is confirmed.

Most epidemiologic studies investigating fetal abnormalities following antihypertensive exposure in the first trimester have not specifically differentiated between drugs affecting the renin-angiotensin system and other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is crucial to optimize outcomes for both the mother and fetus.

In cases where no suitable alternative therapy exists for a patient requiring treatment with renin-angiotensin system-affecting drugs, the mother should be informed of the potential risks to the fetus. Serial ultrasound examinations should be conducted to monitor the intra-amniotic environment. If oligohydramnios is detected, fosinopril and hydrochlorothiazide should be discontinued unless their continuation is deemed lifesaving for the mother. It is important to note that oligohydramnios may not manifest until after the fetus has sustained irreversible injury. Infants with a history of in utero exposure to these medications should be closely monitored for hypotension, oliguria, and hyperkalemia.

Intrauterine exposure to thiazide diuretics has been linked to fetal or neonatal jaundice, thrombocytopenia, and potentially other adverse reactions observed in adults. However, no teratogenic effects of fosinopril or hydrochlorothiazide were identified in studies involving pregnant rats and rabbits, with doses used being significantly higher than the maximum recommended human dose.

Lactation

Both fosinopril and hydrochlorothiazide are excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, lactating mothers should consider whether to discontinue nursing or to discontinue fosinopril sodium and hydrochlorothiazide. This decision should take into account the importance of the medication to the mother.

Renal Impairment

Fosinopril sodium and hydrochlorothiazide should be used with caution in patients with severe renal disease, as thiazides may precipitate azotemia in these individuals, and the effects of repeated dosing may be cumulative. In patients with severe congestive heart failure, where renal function may depend on the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme (ACE) inhibitors, including fosinopril, may lead to oliguria, progressive azotemia, and, in rare cases, acute renal failure or death.

In studies involving 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 the ACE inhibitor therapy, concomitant diuretic therapy, or both. Therefore, when initiating treatment with fosinopril sodium and hydrochlorothiazide in such patients, renal function should be closely monitored during the first few weeks of therapy.

Additionally, some hypertensive patients treated with ACE inhibitors, even in the absence of apparent preexisting renal vascular disease, have experienced minor and transient increases in blood urea nitrogen and serum creatinine, particularly when the ACE inhibitor is administered alongside a diuretic. In these cases, a dosage reduction of fosinopril sodium and hydrochlorothiazide may be necessary. It is essential that the evaluation of hypertensive patients includes a thorough assessment of renal function.

Hepatic Impairment

Patients with hepatic impairment should be treated with caution when prescribed fosinopril sodium and hydrochlorothiazide. The metabolism of fosinopril to its active form, fosinoprilat, is primarily dependent on hepatic esterases; therefore, patients with compromised liver function may experience elevated plasma levels of fosinopril.

In clinical studies involving patients with alcoholic or biliary cirrhosis, it was observed that while the rate of hydrolysis to fosinoprilat was reduced, the clearance of fosinoprilat was also diminished, resulting in an approximately doubled area under the fosinoprilat-time curve. This indicates that dosage adjustments may be necessary for this patient population to avoid potential toxicity.

Additionally, there have been rare reports of a syndrome associated with ACE inhibitors, which begins with cholestatic jaundice and can progress to fulminant hepatic necrosis, and in some cases, death. If a patient receiving fosinopril sodium and hydrochlorothiazide develops jaundice or shows marked elevation of hepatic enzymes, it is imperative to discontinue the medication and ensure appropriate medical follow-up.

Due to the potential for minor alterations in fluid and electrolyte balance to precipitate hepatic coma, careful monitoring of patients with impaired hepatic function or progressive liver disease is essential. Regular assessment of liver function tests should be conducted to ensure patient safety and to guide any necessary adjustments in therapy.

Overdosage

In cases of overdose involving fosinopril sodium and hydrochlorothiazide tablets, it is essential to consult a certified Regional Poison Control Center for the most current treatment recommendations. Contact information for these centers can be found in the Physicians’ Desk Reference (PDR). When managing an overdose, healthcare professionals should consider the potential for multiple-drug overdoses, drug-drug interactions, and atypical drug kinetics in the patient.

Currently, there is no specific information available regarding the treatment of overdose with fosinopril sodium and hydrochlorothiazide. Management should be symptomatic and supportive. It is advised to discontinue therapy with these medications and closely observe the patient. Treatment should address dehydration, electrolyte imbalances, and hypotension according to established medical protocols.

Animal studies have indicated that single oral doses of 2600 mg/kg of fosinopril resulted in significant lethality in rats, while doses of up to 2750 mg/kg of hydrochlorothiazide were generally survivable. These doses far exceed the maximum recommended daily dose of either medication, highlighting the potential severity of overdose.

Human data on fosinopril overdose are limited, but hypotension is likely the most common manifestation. In cases of hydrochlorothiazide overdose, symptoms typically include dehydration and electrolyte depletion, such as hypokalemia, hypochloremia, and hyponatremia. If the patient has also received digitalis, hypokalemia may exacerbate the risk of cardiac arrhythmias.

Laboratory assessments of serum levels of fosinopril and its metabolites are not commonly available, and such measurements do not play a defined role in the management of fosinopril overdose. Furthermore, there is no evidence to support the use of physiological maneuvers, such as altering urine pH, to enhance the elimination of fosinopril and its metabolites. Hemodialysis or peritoneal dialysis is also ineffective in removing fosinoprilat from the body.

While angiotensin II could theoretically act as a specific antagonist or antidote in fosinopril overdose, it is largely unavailable outside of specialized research settings. Given that the hypotensive effects of fosinopril result from vasodilation and effective hypovolemia, it is reasonable to manage fosinopril overdose with the infusion of normal saline solution to restore volume and stabilize blood pressure.

Nonclinical Toxicology

No teratogenic effects were observed in nonclinical studies. In reproductive studies, male and female rats treated with up to 60 mg/kg daily exhibited no adverse reproductive effects. At doses four times higher, slight increases in pairing time were noted; this higher dose corresponds to approximately 125 times (body surface area basis) or 600 times (body weight basis) the dose received by a 50 kg human taking 20 mg daily. Additionally, no adverse effects on fertility were detected in rats and mice receiving dietary hydrochlorothiazide prior to mating and throughout gestation at doses up to 4 mg/kg/day for rats and 100 mg/kg/day for mice, which are 3.2 times and 400 times greater than the dose received by a 50 kg human taking 12.5 mg daily, respectively.

Reproductive studies and long-term carcinogenicity studies involving fosinopril sodium and hydrochlorothiazide have not been conducted. The combination of fosinopril and hydrochlorothiazide was found to be non-mutagenic in the Ames microbial mutagen test, the mouse lymphoma forward mutation assay, and the Chinese hamster ovary cell cytogenetic assay. Furthermore, it was not genotoxic in a mouse micronucleus test conducted in vivo.

Carcinogenicity studies revealed no evidence of carcinogenicity when fosinopril was administered in the diet to rats and mice for up to 24 months at doses up to 400 mg/kg/day. This highest dose is approximately 250 times the maximum human dose of 80 mg, based on a 50 kg subject, and 20 to 40 times the maximum human dose when adjusted for body surface area. Neither fosinopril nor its active metabolite, fosinoprilat, demonstrated mutagenicity in the Ames test, the mouse lymphoma forward mutation assay, or a mitotic gene conversion assay. Additionally, fosinopril was not genotoxic in a mouse micronucleus test in vivo or a mouse bone marrow cytogenetic assay in vivo.

In the Chinese hamster ovary cell cytogenetic assay, fosinopril increased the frequency of chromosomal aberrations at a toxic concentration without metabolic activation; however, no increase was observed at lower concentrations without metabolic activation or at any concentration with metabolic activation.

Under the National Toxicology Program, rats and mice were administered hydrochlorothiazide for two years at doses up to 100 mg/kg/day for rats and 600 mg/kg/day for mice. These highest doses correspond to approximately 2400 times (mice) or 400 times (rats) the fosinopril sodium and hydrochlorothiazide dose of 12.5 mg given to a 50 kg subject, and 226 times (mice) and 82 times (rats) when adjusted for body surface area. These studies found no evidence of carcinogenicity in rats or female mice, although equivocal evidence of hepatocarcinogenicity was noted in male mice.

Hydrochlorothiazide was not genotoxic in various in vitro assays, including the Ames assay using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538, the Chinese Hamster Ovary test for chromosomal aberrations, or in vivo assays involving mouse germinal cell chromosomes and Chinese hamster bone marrow chromosomes. However, positive results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the Mouse Lymphoma Cell (mutagenicity) assays at concentrations ranging from 43 to 1300 mg/mL. Additionally, positive results were also observed in the Aspergillus nidulans nondisjunction assay using an unspecified concentration of hydrochlorothiazide.

Postmarketing Experience

Patients receiving ACE inhibitors, including fosinopril sodium and hydrochlorothiazide, have reported a range of adverse reactions, some of which may be serious.

Angioedema has been observed in various forms, including head and neck angioedema affecting the face, extremities, lips, tongue, glottis, and larynx. Notably, angioedema associated with laryngeal edema can be fatal. In cases where laryngeal stridor or angioedema of the face, tongue, or glottis occurs, it is recommended that treatment with fosinopril sodium and hydrochlorothiazide be discontinued immediately, and appropriate therapy initiated. Additionally, intestinal angioedema has been reported, with patients presenting abdominal pain, sometimes without prior facial angioedema and with normal C-1 esterase levels. Diagnosis was confirmed through abdominal CT scans, ultrasounds, or surgical procedures, with symptoms resolving upon cessation of the ACE inhibitor.

Anaphylactoid reactions have been documented in patients undergoing desensitization treatment with hymenoptera venom while on ACE inhibitors, with life-threatening reactions occurring. These reactions were avoided when ACE inhibitors were temporarily withheld but recurred upon inadvertent rechallenge. Furthermore, anaphylactoid reactions have also been reported in patients undergoing dialysis with high-flux membranes while concurrently treated with an ACE inhibitor.

Symptomatic hypotension is another potential adverse effect associated with fosinopril sodium and hydrochlorothiazide, particularly in patients who are volume- and/or salt-depleted due to prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting.

Neutropenia and agranulocytosis have been associated with another ACE inhibitor, captopril, particularly in patients with renal impairment or collagen-vascular diseases. While available data from clinical trials of fosinopril are insufficient to definitively exclude the risk of agranulocytosis, caution is advised.

Other adverse events reported with ACE inhibitors include cardiac arrest, pancytopenia, hemolytic anemia, aplastic anemia, thrombocytopenia, bullous pemphigus, exfoliative dermatitis, and a syndrome characterized by symptoms such as arthralgia, arthritis, vasculitis, serositis, myalgia, fever, rash or other dermopathy, positive ANA titer, leukocytosis, eosinophilia, and elevated ESR.

Patient Counseling

Healthcare providers should advise patients to discontinue fosinopril and hydrochlorothiazide as soon as pregnancy is detected. It is important to inform patients that medications affecting the renin-angiotensin system can cause injury and death to a developing fetus. Female patients of childbearing age should be made aware of the potential consequences of exposure to these medications during pregnancy and should discuss treatment options if they are planning to become pregnant.

Patients should be encouraged to report any pregnancies to their physicians as soon as possible. Additionally, healthcare providers should caution patients that lightheadedness may occur, particularly during the initial days of therapy, and that this should be reported to the prescribing physician. In the event of syncope, patients should be instructed to discontinue the use of fosinopril and hydrochlorothiazide until they have consulted with their physician.

All patients should be warned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to a significant drop in blood pressure, which may result in lightheadedness or syncope. Patients receiving fosinopril and hydrochlorothiazide should also be advised against using potassium supplements or salt substitutes containing potassium without prior consultation with their prescribing physician. Furthermore, patients should be instructed to promptly report any signs of infection, such as sore throat or fever, as these may indicate neutropenia.

Storage and Handling

The product is supplied in a container that must be stored at a temperature range of 20 to 25° C (68 to 77° F), in accordance with USP Controlled Room Temperature guidelines. It is essential to protect the product from moisture; therefore, the bottle should be kept tightly closed at all times to maintain its integrity and efficacy.

Additional Clinical Information

Therapy with fosinopril sodium and hydrochlorothiazide should be temporarily interrupted for several days prior to conducting tests for parathyroid function.

Additionally, clinicians should be aware that fosinopril may lead to falsely low serum digoxin level measurements when using the Digi-Tab® (Nuclear Medical) RIA Kit. However, the accuracy of the Coat-A-Count® (Diagnostic Products Corporation) kit remains unaffected by fosinopril.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Fosinopril Sodium and Hydrochlorothiazide as submitted by Ranbaxy Pharmaceuticals Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)