Fosinopril sodium/Hydrochlorothiazide

Description

Fosinopril sodium, USP is a white to off-white crystalline powder with a molecular weight of 408.48 g/mol. It is soluble in water (> 100 mg/mL), ethanol, and methanol, and slightly soluble in hexane. The chemical name for fosinopril sodium is L-proline, 4-cyclohexyl-1-[[2-methyl-1-(1-oxopropoxy)-propoxy-(4-phenylbutyl)-phosphinyl] acetyl]-, sodium salt, trans. The active metabolite, fosinoprilat, is a non-sulfhydryl angiotensin-converting enzyme inhibitor, formed through hepatic cleavage of the ester group.

Hydrochlorothiazide, USP is a white or practically white, practically odorless crystalline powder with a chemical name of 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. It is 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. Hydrochlorothiazide functions as a thiazide diuretic.

Fosinopril sodium and hydrochlorothiazide tablets are a combination formulation available for oral administration in two strengths: 10 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide, USP, and 20 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide, USP. The inactive ingredients in the tablets include lactose anhydrous, crospovidone, povidone USP, microcrystalline cellulose, sodium stearate, and talc USP.

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

In clinical trials evaluating the combination therapy of fosinopril and hydrochlorothiazide, fosinopril was administered in doses of 2.5 mg to 40 mg, while hydrochlorothiazide was given in doses of 5 mg to 37.5 mg. The antihypertensive effects of the combination therapy were observed to increase with higher doses of either component.

For patients whose blood pressure remains inadequately controlled with monotherapy using either fosinopril or hydrochlorothiazide, a switch to combination therapy with fosinopril sodium and hydrochlorothiazide tablets is recommended. Dosage adjustments should be guided by clinical response. Controlled clinical trials have demonstrated that the addition of 12.5 mg of hydrochlorothiazide to a regimen of 10 mg to 20 mg of fosinopril typically results in a significant additional reduction in seated diastolic blood pressure at 24 hours post-dosing.

On average, the antihypertensive effect of the combination of 10 mg of fosinopril with 12.5 mg of hydrochlorothiazide is comparable to the effects achieved with monotherapy using 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 serum creatinine levels exceeding 3 mg/dL (265 µmol/L), the use of loop diuretics is preferred over thiazides; therefore, fosinopril sodium and hydrochlorothiazide tablets are not recommended in this population. In patients with lesser degrees of renal impairment, the combination may be used without any alteration in dosage.

Contraindications

Fosinopril sodium and hydrochlorothiazide tablets are contraindicated in patients who are anuric. Additionally, these tablets should not be used 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 tablets, may experience serious adverse reactions, including anaphylactoid and possibly related reactions.

Angioedema Angioedema affecting the face, extremities, lips, tongue, glottis, and larynx has been reported. Notably, angioedema associated with laryngeal edema can be fatal. In the event of laryngeal stridor or angioedema, treatment should be discontinued immediately, and appropriate therapy should be administered without delay. Additionally, intestinal angioedema has been observed in patients treated with ACE inhibitors, often presenting with abdominal pain, which resolved upon discontinuation of the medication.

Desensitization Reactions Life-threatening anaphylactoid reactions have occurred in patients undergoing desensitization while on ACE inhibitors.

Hypotension ACE inhibitors can cause symptomatic hypotension, particularly in patients who are volume- and/or salt-depleted. Close monitoring is essential for patients with congestive heart failure to manage this risk effectively.

Renal Function Caution is advised when using ACE inhibitors in patients with severe renal disease. Renal function should be monitored during the first few weeks of therapy to detect any deterioration.

Neutropenia and Agranulocytosis In patients with collagen-vascular disease, monitoring of white blood cell counts is recommended due to the risk of neutropenia and agranulocytosis.

Fetal Toxicity The use of ACE inhibitors during the second and third trimesters of pregnancy can adversely affect fetal renal function, leading to increased morbidity and mortality. Therefore, treatment should be discontinued as soon as pregnancy is detected.

Hepatic Function In cases of jaundice or marked elevation of hepatic enzymes, discontinuation of the medication is necessary, and appropriate medical follow-up should be sought.

Electrolyte Monitoring Initial and periodic determinations of serum electrolytes are recommended to detect potential electrolyte imbalances during therapy.

Laboratory Considerations Therapy should be interrupted for a few days prior to tests assessing parathyroid function. Additionally, fosinopril may lead to falsely low measurements of serum digoxin levels when using certain testing kits.

In summary, healthcare professionals should remain vigilant for these warnings and precautions, ensuring appropriate monitoring and intervention as necessary to mitigate risks associated with the use of ACE inhibitors.

Side Effects

Patients may experience a range of adverse reactions while using this medication, which can be categorized by seriousness and frequency.

Common adverse reactions reported include headache (0.3%), cough (0.3%), and fatigue (0.2%). In placebo-controlled studies, additional reactions that may be possibly or probably drug-related include general symptoms such as chest pain, weakness, fever, and viral infections.

Cardiovascular reactions are notable, with orthostatic hypotension occurring in 1.8% of patients taking fosinopril sodium hydrochlorothiazide tablets compared to 0.3% in placebo patients. Other cardiovascular effects may include edema, flushing, rhythm disturbances, syncope, angina, myocardial infarction, cerebrovascular accidents, hypertensive crises, hypotension, and claudication.

Dermatologic reactions may manifest as pruritus, rash, urticaria, and photosensitivity. Endocrine and metabolic reactions can include sexual dysfunction, changes in libido, breast mass, and gout. Gastrointestinal adverse reactions may consist of nausea/vomiting, diarrhea, dyspepsia/heartburn, abdominal pain, gastritis/esophagitis, pancreatitis, hepatitis, dysphagia, abdominal distention, flatulence, appetite or weight changes, and dry mouth.

Immunologic reactions such as angioedema are significant and warrant attention (see Warnings: Head and Neck Angioedema and Intestinal Angioedema). Musculoskeletal reactions may include myalgia, muscle cramps, and arthralgia. Neurologic and psychiatric reactions can involve somnolence, depression, memory disturbances, tremor, confusion, mood changes, and sleep disturbances. Respiratory reactions may present as sinus congestion, pharyngitis, rhinitis, bronchospasm, laryngitis/hoarseness, epistaxis, and in two patients, a symptom complex of cough, bronchospasm, and eosinophilia.

Special senses may be affected, with reports of tinnitus, vision disturbances, taste disturbances, and eye irritation. Urogenital reactions can include urinary tract infections, urinary frequency, dysuria, and renal insufficiency. Laboratory test abnormalities may show changes in serum electrolytes, uric acid, glucose, magnesium, cholesterol, triglycerides, calcium, and neutropenia, as well as transient elevations of BUN and creatinine, leukopenia, eosinophilia, and elevations in liver function tests (transaminases, LDH, alkaline phosphatase, and serum bilirubin).

Warnings associated with this medication include the risk of anaphylactoid reactions, such as angioedema of the face, extremities, lips, tongue, glottis, and larynx, which can be fatal. Symptomatic hypotension may occur, particularly in volume-depleted patients. Caution is advised in patients with severe renal disease, as the medication may precipitate azotemia. Monitoring of white blood cell counts is recommended in patients with collagen-vascular disease due to the risk of neutropenia or agranulocytosis.

Additionally, hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma in white patients taking large cumulative doses.

Drug Interactions

Concomitant use of potassium supplements or potassium-sparing diuretics (e.g., spironolactone, amiloride, triamterene) with fosinopril sodium and hydrochlorothiazide tablets 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 should be monitored frequently.

The coadministration of lithium with fosinopril sodium and hydrochlorothiazide tablets has been associated with increased serum lithium levels and a heightened risk of lithium toxicity, particularly when a thiazide diuretic is also used. Therefore, caution is advised, and regular monitoring of serum lithium levels is recommended.

Antacids containing aluminum hydroxide, magnesium hydroxide, and simethicone may impair the absorption of fosinopril, resulting in reduced serum levels and urinary excretion of fosinoprilat. If antacids are required, dosing should be separated by at least 2 hours.

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 tablets.

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 any clinically significant effects of fosinopril on the serum concentration or clinical effects of warfarin.

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 antihypertensive, diuretic, and natriuretic effects of thiazide diuretics may be diminished when administered concurrently with nonsteroidal anti-inflammatory agents, although the specific impact on the antihypertensive effect of fosinopril sodium and hydrochlorothiazide tablets has not been evaluated.

Hydrochlorothiazide may reduce 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.

The 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 renal function changes, including acute renal failure. Patients receiving fosinopril and hydrochlorothiazide in conjunction with other RAS-affecting agents should be closely monitored for blood pressure, renal function, and electrolyte levels.

Aliskiren should not be co-administered with fosinopril and hydrochlorothiazide in patients with diabetes or those with renal impairment (GFR <60 mL/min).

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 methods.

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 and adolescents.

Geriatric Use

Clinical studies of fosinopril sodium-hydrochlorothiazide did not include a sufficient number of subjects aged 65 and older to determine whether this population responds differently compared to younger subjects. However, other reported clinical experiences have not identified significant differences in responses between elderly patients and their younger counterparts.

In general, dose selection for geriatric patients should be approached with caution. It is advisable to initiate treatment at the lower end of the dosing range, taking into account the increased likelihood of diminished 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

The safety of fosinopril sodium and hydrochlorothiazide tablets during pregnancy has not been established due to the absence of reproductive studies and long-term carcinogenicity studies. Available data indicate that the combination of fosinopril and hydrochlorothiazide is not mutagenic based on various tests. Fosinopril has demonstrated no carcinogenic potential in rats and mice at doses up to 400 mg/kg/day, and no adverse reproductive effects were observed in male and female rats treated with doses up to 60 mg/kg daily. However, at doses four times higher, slight increases in pairing time were noted in rats, suggesting a potential impact on reproductive performance at elevated doses.

Hydrochlorothiazide has also shown no genotoxicity in various in vitro and in vivo assays. Furthermore, no adverse effects on fertility were observed in rats and mice that 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, healthcare professionals should exercise caution when prescribing fosinopril sodium and hydrochlorothiazide tablets to pregnant patients. The potential risks and benefits should be carefully weighed, and alternative treatments may be considered, especially during the first trimester. Women of childbearing potential should be advised to use effective contraception while on this medication.

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 tablets. This decision should take into account the importance of the medication to the mother.

Renal Impairment

Fosinopril sodium and hydrochlorothiazide tablets should be used with caution in patients with severe renal disease, as thiazides may precipitate azotemia in this population, and the effects of repeated dosing may be cumulative. In patients with severe congestive heart failure, where renal function may rely 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 linked to 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, renal function should be closely monitored during the initial weeks of therapy with fosinopril sodium and hydrochlorothiazide tablets in such patients.

Additionally, some hypertensive patients treated with ACE inhibitors, even without 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. A dosage reduction of fosinopril sodium and hydrochlorothiazide tablets may be necessary in these cases.

Evaluation of renal function should be a routine part of the assessment for hypertensive patients. Furthermore, monitoring of white blood cell counts is advisable in patients with collagen-vascular disease, especially if the disease is associated with impaired renal function.

Hepatic Impairment

Patients with hepatic impairment should be treated with caution when prescribed fosinopril sodium and hydrochlorothiazide tablets. 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 patients with significant liver impairment may require careful monitoring and potential dosage adjustments to avoid adverse effects.

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. The underlying mechanism of this syndrome remains unclear. Therefore, if a patient receiving fosinopril sodium and hydrochlorothiazide tablets develops jaundice or shows marked elevation of hepatic enzymes, it is imperative to discontinue the medication and ensure appropriate medical follow-up.

Given these considerations, it is essential for healthcare providers to closely monitor patients with impaired hepatic function or progressive liver disease, as even minor alterations in fluid and electrolyte balance may precipitate hepatic coma.

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 affected patients.

Currently, there is no specific treatment protocol established for the overdosage of fosinopril sodium and hydrochlorothiazide tablets. Management should be primarily symptomatic and supportive. It is recommended that therapy with these tablets be discontinued, and the patient should be closely monitored. Attention should be given to managing dehydration, electrolyte imbalances, and hypotension according to established medical procedures.

Toxicological studies in rats indicate that 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 of either drug, highlighting the potential severity of overdose situations.

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 routinely available and do not play a 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 in fosinopril overdose, it is largely inaccessible outside of specialized research settings. Given that the hypotensive effects of fosinopril result from vasodilation and effective hypovolemia, the administration of normal saline solution is a reasonable approach to managing fosinopril overdose.

Nonclinical Toxicology

No specific teratogenic effects have been identified in nonclinical studies. In terms of non-teratogenic effects, reproductive studies indicated that there were no adverse reproductive effects observed in male and female rats treated with hydrochlorothiazide at doses up to 60 mg/kg daily. However, at doses four times higher, slight increases in pairing time were noted. Additionally, 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.

Reproductive studies and long-term carcinogenicity studies involving fosinopril sodium and hydrochlorothiazide tablets 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, this 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 up to 400 mg/kg/day. 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 shown 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.

Hydrochlorothiazide demonstrated no genotoxicity in various in vitro assays, including those using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (Ames assay), the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, and in vivo assays involving mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. However, positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the Mouse Lymphoma Cell (mutagenicity) assays using hydrochlorothiazide concentrations ranging from 43 to 1300 mg/mL.

Under the auspices of 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 studies revealed no evidence of carcinogenicity in rats or female mice, although equivocal evidence of hepatocarcinogenicity was noted in male mice.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of angiotensin-converting enzyme (ACE) inhibitors and thiazide diuretics.

Angioedema affecting the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors, with laryngeal edema posing a potential risk of fatality. Additionally, intestinal angioedema has been documented in some patients, who presented with abdominal pain, with or without nausea or vomiting. Notably, these patients may not have a prior history of facial angioedema, and C-1 esterase levels were found to be normal. Diagnosis of intestinal angioedema was achieved through abdominal CT scans, ultrasounds, or surgical intervention, with symptom resolution following the discontinuation of the ACE inhibitor.

Anaphylactoid reactions have been observed in patients undergoing dialysis with high-flux membranes while concurrently treated with ACE inhibitors. Similar reactions have also been reported in patients receiving 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, and exfoliative dermatitis. A syndrome characterized by a combination of arthralgia/arthritis, vasculitis, serositis, myalgia, fever, rash or other dermopathy, positive ANA titer, leukocytosis, eosinophilia, and elevated ESR has also been reported.

Furthermore, hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC). Data from a study conducted in the Sentinel System indicated that the increased risk was predominantly observed in white patients receiving large cumulative doses. The overall risk for SCC in the general population was estimated at 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

Patients should be advised to discontinue fosinopril and hydrochlorothiazide as soon as pregnancy is detected. It is important to inform them that drugs acting directly on the renin-angiotensin system can cause injury and even death to the developing fetus. Patients should be made aware of the potential risks to the fetus if there are no appropriate alternatives to therapy with these medications.

In cases where oligohydramnios is observed, healthcare providers should recommend performing serial ultrasound examinations to assess the intra-amniotic environment. Additionally, infants with a history of in utero exposure to fosinopril and hydrochlorothiazide should be closely monitored for signs of hypotension, oliguria, and hyperkalemia.

Patients must be instructed to report immediately any signs or symptoms of angioedema, such as swelling of the face, eyes, lips, or tongue, or difficulty breathing. They should be advised not to take any additional doses of the medication until they have consulted with their prescribing physician.

It is essential to inform patients that lightheadedness may occur, particularly during the initial days of therapy, and they should report this to their physician. If syncope occurs, patients should discontinue the medication and seek medical advice. Furthermore, patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to a significant drop in blood pressure, resulting in lightheadedness and potential syncope.

Patients should also be advised against using potassium supplements or salt substitutes containing potassium without prior consultation with their prescribing physician. They should promptly report any signs of infection, such as a sore throat or fever, as these may indicate neutropenia.

For those taking hydrochlorothiazide, it is important to instruct them to protect their skin from sun exposure and to undergo regular skin cancer screenings.

Storage and Handling

The product is supplied in a tightly sealed bottle to protect against moisture. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

For dispensing, a tight, light-resistant container is required, which must also include a child-resistant closure as mandated. Proper handling and storage conditions are essential to maintain the integrity of the product.

Additional Clinical Information

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

Additionally, clinicians should be aware that fosinopril may lead to falsely low measurements of serum digoxin levels when using the DIGI-TAB® (Nuclear Medical) RIA Kit. However, the accuracy of the COAT-A-COUNT® (Diagnostic Products Corporation) kit remains unaffected.

FDA Insert (PDF)

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

View full prescribing information (PDF)