Fosinopril sodium/Hydrochlorothiazide

Description

Fosinopril sodium, USP is a white to almost white powder with a molecular formula of C30H45NNaO7P and a molecular weight of 585.65. It is highly soluble in water (>100 mg/mL), ethanol, and methanol, while being slightly soluble in hexane. Chemically, it is designated as L-proline, 4-cyclohexyl-1-[[2-methyl-1-(1-oxopropoxy)propoxy2-methyl-1-(1-oxopropoxy)propoxyphosphinyl]acetyl]-, sodium salt, trans-. Fosinopril is metabolized to its active form, fosinoprilat, a non-sulfhydryl angiotensin-converting enzyme inhibitor, through hepatic cleavage of the ester group.

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

Fosinopril sodium and hydrochlorothiazide tablets, USP are formulated as a combination of fosinopril sodium, USP and hydrochlorothiazide, USP, available for oral administration in two strengths: 10 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide per tablet, and 20 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide per tablet. The inactive ingredients include lactose anhydrous, ferric oxide red, ferric oxide yellow, croscarmellose sodium, povidone, isopropyl alcohol, glyceryl distearate, and sodium lauryl sulfate.

Uses and Indications

Fosinopril sodium and hydrochlorothiazide tablets are indicated for the treatment of hypertension. This fixed-dose combination is not indicated for initial therapy.

Dosage and Administration

Fosinopril is administered as a once-daily dose ranging from 10 mg to 80 mg. Hydrochlorothiazide is given in daily doses of 12.5 mg to 50 mg. In clinical trials evaluating the combination therapy of fosinopril and hydrochlorothiazide, fosinopril doses varied from 2.5 mg to 40 mg, while hydrochlorothiazide doses ranged from 5 mg to 37.5 mg.

When transitioning to combination therapy, 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 has been shown to provide an additional reduction in seated diastolic blood pressure 24 hours post-dosing.

For patients with mild to moderate renal impairment, fosinopril sodium and hydrochlorothiazide tablets can be utilized without necessitating any changes in dosage. It is essential for healthcare professionals to monitor the patient's response and adjust the treatment regimen accordingly to achieve optimal therapeutic outcomes.

Contraindications

Fosinopril sodium and hydrochlorothiazide tablets are contraindicated in patients who are anuric. Additionally, the use of this medication 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, may experience a range of serious adverse reactions, necessitating careful monitoring and management.

Anaphylactoid and Angioedema Reactions Anaphylactoid reactions, including potentially life-threatening angioedema, have been reported in patients treated with ACE inhibitors. Angioedema may affect various regions, including the face, extremities, lips, tongue, glottis, and larynx. In cases where laryngeal stridor or significant angioedema occurs, immediate discontinuation of the ACE inhibitor is required, along with the initiation of appropriate therapy. If there is a risk of airway obstruction due to involvement of the tongue, glottis, or larynx, prompt administration of subcutaneous epinephrine (1:1000) is essential. Additionally, intestinal angioedema has been documented, presenting as abdominal pain, which resolved upon cessation of the ACE inhibitor.

Anaphylactoid Reactions During Desensitization and Membrane Exposure Patients undergoing desensitization therapy while on ACE inhibitors may experience life-threatening anaphylactoid reactions. Furthermore, similar reactions have been noted in patients undergoing dialysis with high-flux membranes while receiving ACE inhibitors.

Serum Electrolyte Monitoring It is crucial to perform initial and periodic assessments of serum electrolytes to identify potential imbalances. Derangements in serum electrolytes can occur, and monitoring should be conducted at appropriate intervals. Additionally, thiazide diuretics may lead to metabolic disturbances, including reduced glucose tolerance and elevated serum levels of cholesterol, triglycerides, and uric acid.

Laboratory Test Considerations Before conducting tests of parathyroid function, therapy with fosinopril sodium and hydrochlorothiazide should be interrupted for several days. It is also important to note that fosinopril may cause falsely low serum digoxin measurements when using the Digi-Tab RIA Kit.

Emergency Medical Assistance In the event of laryngeal stridor or angioedema affecting the face, tongue, or glottis, immediate discontinuation of treatment is necessary, along with the initiation of appropriate medical intervention.

Management of Hypotension Should hypotension occur, the patient should be positioned supine, and if necessary, treated with an intravenous infusion of physiological saline. Prompt medical consultation is advised to ensure appropriate management.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. The most common adverse reactions, occurring in more than 2% of participants, include headache (7%), cough (5.6%), fatigue (3.9%), dizziness (3.2%), upper respiratory infection (2.3%), and musculoskeletal pain (2%).

Other adverse reactions, with an incidence of 0.5% to less than 2%, encompass a variety of systems. General reactions may include chest pain, weakness, fever, and viral infections. Cardiovascular events such as orthostatic hypotension (1.8% in treated patients), edema, flushing, rhythm disturbances, and syncope have also been reported. Dermatologic reactions include pruritus and rash, while endocrine/metabolic issues may manifest as sexual dysfunction, changes in libido, and breast mass. Gastrointestinal disturbances can present as nausea/vomiting, diarrhea, dyspepsia/heartburn, abdominal pain, and gastritis/esophagitis.

Immunologic reactions, including angioedema, have been noted (see Warnings). Musculoskeletal complaints may involve myalgia or muscle cramps. Neurologic and psychiatric effects can include somnolence, depression, and numbness/paresthesia. Respiratory issues such as sinus congestion, pharyngitis, and rhinitis have also been observed. Special senses may be affected, with reports of tinnitus. Urogenital reactions include urinary tract infections, urinary frequency, and dysuria.

Serious warnings include the risk of angioedema, which can affect the face, extremities, lips, tongue, glottis, and larynx, and may be fatal if associated with laryngeal edema. Intestinal angioedema may present as abdominal pain, with or without nausea or vomiting, and symptoms typically resolve upon discontinuation of the ACE inhibitor.

Additional adverse reactions of note include cardiovascular events such as angina, myocardial infarction, cerebrovascular accidents, hypertensive crises, hypotension, and claudication. Dermatologic reactions may also include urticaria and photosensitivity. Endocrine/metabolic issues can lead to gout, while gastrointestinal complications may involve pancreatitis, hepatitis, dysphagia, abdominal distention, flatulence, appetite or weight changes, and dry mouth. Hematologic reactions such as lymphadenopathy have been reported, alongside musculoskeletal complaints like arthralgia. Neurologic and psychiatric effects may include memory disturbances, tremors, confusion, mood changes, and sleep disturbances. Respiratory reactions can involve bronchospasm, laryngitis/hoarseness, epistaxis, and eosinophilia. Special senses may experience vision and taste disturbances, as well as eye irritation. Urogenital issues may lead to renal insufficiency.

Laboratory test abnormalities have been noted, including changes in serum electrolytes, uric acid, glucose, magnesium, cholesterol, triglycerides, and calcium, as well as neutropenia. Monitoring of white blood cell counts should be considered in patients with collagen-vascular disease.

Drug Interactions

Concomitant use of potassium supplements or potassium-sparing diuretics, such as spironolactone, amiloride, and triamterene, with fosinopril sodium and hydrochlorothiazide may lead to variable effects on serum potassium levels, including potential hyperkalemia. If such combinations are necessary, they should be administered with caution, and serum potassium levels must be monitored frequently.

The coadministration of lithium with fosinopril sodium and hydrochlorothiazide can result in increased serum lithium levels and a heightened risk of lithium toxicity due to reduced renal clearance caused by thiazides. Therefore, careful monitoring of serum lithium levels is advised when these medications are used together.

Antacids containing aluminum hydroxide, magnesium hydroxide, and simethicone may impair the absorption of fosinopril, leading to reduced serum levels and urinary excretion of fosinoprilat. If antacids are required, it is recommended that they be administered at least 2 hours apart from fosinopril.

Rare instances of nitritoid reactions, characterized by facial flushing, nausea, vomiting, and hypotension, have been reported in patients receiving injectable gold (sodium aurothiomalate) alongside ACE inhibitors, including fosinopril sodium and hydrochlorothiazide. Caution is advised when these therapies are combined.

The bioavailability of unbound fosinoprilat remains unaffected by the coadministration of aspirin, chlorthalidone, cimetidine, digoxin, metoclopramide, nifedipine, propranolol, propantheline, or warfarin. Interaction studies have not demonstrated clinically significant effects of fosinopril on warfarin serum concentrations or clinical outcomes.

Thiazide diuretics may diminish arterial responsiveness to norepinephrine; however, this effect does not compromise the therapeutic efficacy of norepinephrine. Conversely, thiazides may enhance responsiveness to tubocurarine.

The concurrent use of nonsteroidal anti-inflammatory agents may reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics. The impact of these agents on the antihypertensive effects of fosinopril sodium and hydrochlorothiazide has not been specifically studied.

Hydrochlorothiazide may decrease the effectiveness of methenamine by alkalinizing the urine. Additionally, the absorption of hydrochlorothiazide is significantly impaired when administered with anionic exchange resins such as cholestyramine or colestipol, with reductions in absorption of up to 85% and 43%, respectively.

Dual blockade of the renin-angiotensin system (RAS) with agents such as angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and renal function changes, including acute renal failure. Patients receiving fosinopril and hydrochlorothiazide alongside other RAS-affecting agents should be closely monitored for blood pressure, renal function, and electrolyte levels. The coadministration 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).

Patients taking hydrochlorothiazide should be advised to protect their skin from sun exposure and to undergo regular skin cancer screenings due to an increased risk of non-melanoma skin cancer associated with this medication.

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 manage 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, indicating a need for caution when considering their use in this population.

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 advisable 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 recommended to ensure safety and efficacy.

Pregnancy

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

No evidence of carcinogenicity was observed when fosinopril was administered in the diet to rats and mice for up to 24 months at doses as high as 400 mg/kg/day. Neither fosinopril nor its active metabolite, fosinoprilat, demonstrated mutagenic properties in the aforementioned assays. However, in the Chinese hamster ovary cell cytogenetic assay, fosinopril did increase the frequency of chromosomal aberrations when tested without metabolic activation at a concentration that was toxic to the cells.

In terms of reproductive effects, no adverse outcomes were noted in male and female rats treated with up to 60 mg/kg daily. At doses four times higher, slight increases in pairing time were observed. Hydrochlorothiazide also did not exhibit genotoxicity in in vitro assays using strains of Salmonella typhimurium or in various in vivo assays. Furthermore, no adverse effects on fertility were reported when rats and mice received 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.

Given the lack of comprehensive reproductive studies and the observed effects at high doses, healthcare professionals should exercise caution when prescribing this combination to pregnant patients or women of childbearing potential. The potential risks and benefits should be carefully considered in these populations.

Lactation

Both fosinopril and hydrochlorothiazide are excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, lactating mothers should make a decision regarding the continuation of breastfeeding or the discontinuation of fosinopril sodium and hydrochlorothiazide. This decision should consider the importance of the medication to the mother’s health.

Renal Impairment

Patients with renal impairment should be treated with caution when using fosinopril sodium and hydrochlorothiazide, particularly in cases of severe renal disease, as thiazides may precipitate azotemia and the effects of repeated dosing can be cumulative.

In individuals with severe congestive heart failure, where renal function may be reliant on the renin-angiotensin-aldosterone system, the use of angiotensin-converting enzyme (ACE) inhibitors, including fosinopril, may lead to oliguria, progressive azotemia, and, in rare instances, acute renal failure or death.

Clinical studies have indicated that hypertensive patients with unilateral or bilateral renal artery stenosis may experience increases in blood urea nitrogen and serum creatinine when treated with ACE inhibitors. These increases are generally reversible upon discontinuation of the ACE inhibitor, diuretic therapy, or both. Therefore, renal function should be closely monitored during the initial weeks of therapy with fosinopril sodium and hydrochlorothiazide in these patients.

Additionally, some hypertensive patients treated with ACE inhibitors, even in the absence of preexisting renal vascular disease, have shown minor and transient increases in blood urea nitrogen and serum creatinine, particularly when combined with diuretics. In such cases, a dosage reduction of fosinopril sodium and hydrochlorothiazide may be necessary.

It is essential to include renal function assessment as part of the evaluation for hypertensive patients.

Hepatic Impairment

Patients with hepatic impairment should be monitored closely when receiving fosinopril sodium and hydrochlorothiazide. Rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and can progress to fulminant hepatic necrosis, and in some cases, death. The mechanism underlying this syndrome remains unclear.

In patients receiving fosinopril sodium and hydrochlorothiazide, the development of jaundice or marked elevation of hepatic enzymes necessitates the immediate discontinuation of the medication and appropriate medical follow-up. Caution is advised when prescribing fosinopril sodium and hydrochlorothiazide to patients with impaired hepatic function or progressive liver disease, as even minor alterations in fluid and electrolyte balance may precipitate hepatic coma.

The metabolism of fosinopril to its active form, fosinoprilat, is primarily dependent on hepatic esterases. Consequently, patients with compromised liver function may experience elevated plasma levels of fosinopril. Clinical studies have indicated that in patients with alcoholic or biliary cirrhosis, the rate of hydrolysis to fosinoprilat is reduced, although the extent of hydrolysis remains unchanged. Furthermore, these patients exhibit reduced clearance of fosinoprilat, resulting in an approximately doubled area under the fosinoprilat-time curve. Therefore, careful consideration of dosage adjustments and ongoing monitoring of liver function is essential in this patient population.

Overdosage

In the event of an overdose involving fosinopril sodium and hydrochlorothiazide tablets, it is crucial to seek guidance from a certified Regional Poison Control Center. Contact information for these centers can be found in the Physicians’ Desk Reference (PDR). Healthcare professionals should be vigilant for the potential of multiple-drug overdoses, drug-drug interactions, and atypical drug kinetics in the patient.

Management of Overdosage

Currently, there is no specific information available regarding the treatment of overdose with fosinopril sodium and hydrochlorothiazide. Management should be primarily symptomatic and supportive. It is recommended that therapy with these medications be discontinued, and the patient should be closely monitored. Key considerations in management include addressing dehydration, electrolyte imbalances, and hypotension through established medical procedures.

Symptoms of Overdosage

In animal studies, single oral doses of 2600 mg/kg of fosinopril resulted in significant lethality, while doses of up to 2750 mg/kg of hydrochlorothiazide were generally survivable. These doses far exceed the maximum recommended daily dose for either drug. In humans, the most frequently observed manifestation of fosinopril overdose is hypotension. For hydrochlorothiazide, common symptoms include dehydration and electrolyte depletion, such as hypokalemia, hypochloremia, and hyponatremia. Notably, if digitalis has been administered, hypokalemia may exacerbate the risk of cardiac arrhythmias.

Laboratory Considerations

Laboratory assessments of serum levels of fosinopril and its metabolites are not commonly available and 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. It is important to note that fosinoprilat is poorly removed from the body via hemodialysis or peritoneal dialysis.

Treatment Options

While angiotensin II could theoretically act as a specific antagonist or antidote in cases of 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

Reproductive studies and long-term carcinogenicity studies with fosinopril sodium and hydrochlorothiazide have 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. Additionally, the combination was not genotoxic in a mouse micronucleus test conducted in vivo.

No evidence of carcinogenicity was observed when fosinopril was administered in the diet to rats and mice for up to 24 months at doses reaching 400 mg/kg/day. On a body weight basis, this highest dose was approximately 250 times the maximum human dose of 80 mg, based on a 50 kg subject. When evaluated on a body surface area basis, this dose corresponds to 20 times (mice) and 40 times (rats) the maximum human dose.

Neither fosinopril nor its active metabolite, fosinoprilat, exhibited mutagenic properties in the Ames microbial mutagen test, the mouse lymphoma forward mutation assay, or a mitotic gene conversion assay. Fosinopril was also found to be non-genotoxic in a mouse micronucleus test in vivo and a mouse bone marrow cytogenetic assay in vivo. However, in the 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. No increase in chromosomal aberrations was noted at lower drug concentrations without metabolic activation or at any concentration with metabolic activation.

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

Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide for two years at doses up to 100 mg/kg/day for rats and 600 mg/kg/day for mice. On a body weight basis, these highest doses were about 2400 times (mice) or 400 times (rats) the fosinopril sodium and 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 and hydrochlorothiazide dose.

These studies revealed no evidence of carcinogenicity in rats or female mice; however, equivocal evidence of hepatocarcinogenicity was noted in male mice. Hydrochlorothiazide was not genotoxic in in vitro assays using various strains of Salmonella typhimurium (Ames assay), the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in in vivo assays involving mouse germinal cell chromosomes, Chinese Hamster bone-marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the Mouse Lymphoma Cell (mutagenicity) assays using concentrations of hydrochlorothiazide ranging from 43 to 1300 mg/mL. Additionally, positive test results were observed in the Aspergillus nidulans nondisjunction assay using an unspecified concentration of hydrochlorothiazide.

No adverse effects on fertility were observed when rats and mice received 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. These doses are from 3.2 times (body surface area basis in rats) to 400 times (body weight basis in mice) greater than the dose received by a 50 kg human receiving 12.5 mg daily.

Postmarketing Experience

Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin-converting enzyme (ACE) inhibitors. Cases of angioedema associated with laryngeal edema can be fatal. In instances of laryngeal stridor or angioedema affecting the face, tongue, or glottis, it is recommended that treatment with fosinopril sodium and hydrochlorothiazide be discontinued immediately, and appropriate therapy should be initiated.

Intestinal angioedema has also been documented in patients receiving ACE inhibitors, presenting with abdominal pain, which may occur with or without nausea or vomiting. Notably, some patients had no prior history of facial angioedema, and C-1 esterase levels were found to be normal. Diagnosis of intestinal angioedema was made through abdominal CT scans, ultrasounds, or surgical procedures, with symptom resolution following the cessation of the ACE inhibitor.

Anaphylactoid reactions have been reported in patients undergoing dialysis with high-flux membranes while concurrently treated with an ACE inhibitor. Additionally, such reactions have been noted in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Neutropenia and agranulocytosis have been associated with thiazide diuretics.

Other adverse effects linked to ACE inhibitors include cardiac arrest, pancytopenia, hemolytic anemia, aplastic anemia, thrombocytopenia, bullous pemphigus, exfoliative dermatitis, and a syndrome characterized by one or more of the following: arthralgia, arthritis, vasculitis, serositis, myalgia, fever, rash or other dermopathy, positive ANA titer, leukocytosis, eosinophilia, and elevated ESR.

Hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer. A study conducted in the Sentinel System indicated that the increased risk was predominantly for squamous cell carcinoma (SCC), particularly in white patients receiving large cumulative doses. The overall increased risk for SCC was approximately one additional case per 16,000 patients per year, while for white patients taking a cumulative dose of ≥50,000 mg, the risk increase was approximately one additional SCC case for every 6,700 patients per year.

Patient Counseling

Healthcare providers should advise patients receiving fosinopril sodium and hydrochlorothiazide to be vigilant for signs of angioedema, including swelling of the face, eyes, lips, or tongue, and difficulty breathing. Patients should be instructed to report any such symptoms immediately and to refrain from taking additional doses until they have consulted with their prescribing physician.

Female patients of childbearing age must be informed about the potential risks associated with the use of fosinopril and hydrochlorothiazide during pregnancy. It is essential to discuss alternative treatment options with women who are planning to become pregnant, and patients should be encouraged to notify their physicians as soon as they become pregnant.

Patients should be cautioned that lightheadedness may occur, particularly during the initial days of therapy. They should report any episodes of lightheadedness or syncope to their prescribing physician, and if syncope occurs, they should discontinue the medication until they have consulted with their healthcare provider.

It is important to instruct patients not to use potassium supplements or salt substitutes containing potassium without prior consultation with their prescribing physician, as this could lead to adverse effects.

Patients should be advised to promptly report any signs of infection, such as sore throat or fever, as these may indicate neutropenia, a potentially serious condition.

For those taking hydrochlorothiazide, healthcare providers should recommend protective measures against sun exposure and encourage regular skin cancer screenings due to the increased risk associated with this medication.

Additionally, therapy with fosinopril sodium and hydrochlorothiazide should be temporarily interrupted for a few days prior to conducting tests of parathyroid function to ensure accurate results.

Lastly, healthcare providers should inform patients that fosinopril may lead to falsely low serum digoxin levels when using the Digi-Tab (Nuclear Medical) RIA Kit, although the accuracy of the Coat-A-Count (Diagnostic Products Corporation) kit remains unaffected.

Storage and Handling

The product is supplied in a container that must be kept tightly closed to protect it from moisture. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) in accordance with USP Controlled Room Temperature guidelines.

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 Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)