Hydrochlorothiazide/Lisinopril

Description

Lisinopril, a synthetic peptide derivative, is chemically described as (S)-1-N2-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline dihydrate. Its empirical formula is C21H31N3O5•2H2O, and it has a molecular weight of 441.53. Lisinopril appears as a white, crystalline powder that is soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol.

Hydrochlorothiazide is identified as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, with an empirical formula of C7H8ClN3O4S2 and a molecular weight of 297.72. It is a white, or practically white, crystalline powder that is slightly soluble in water and freely soluble in sodium hydroxide solution.

Lisinopril and hydrochlorothiazide tablets USP are formulated for oral use in three combinations: 10 mg/12.5 mg, 20 mg/12.5 mg, and 20 mg/25 mg. The inactive ingredients include dibasic calcium phosphate, magnesium stearate, mannitol, pregelatinized starch, and starch (corn). The 10 mg/12.5 mg tablet also contains FD&C Blue No. 2 Aluminum Lake, the 20 mg/12.5 mg tablet contains yellow iron oxide, and the 20 mg/25 mg tablet contains red iron oxide.

Uses and Indications

Lisinopril and hydrochlorothiazide tablets USP are indicated for the treatment of hypertension to lower blood pressure. Effective management of high blood pressure is essential for reducing the risk of both fatal and non-fatal cardiovascular events, particularly strokes and myocardial infarctions.

Control of hypertension should be integrated into a comprehensive cardiovascular risk management strategy, which includes lipid control, diabetes management, antithrombotic therapy, smoking cessation, regular exercise, and limited sodium intake. It is important to note that many patients may require a combination of antihypertensive medications to achieve their blood pressure goals.

Clinical studies have demonstrated that various antihypertensive agents, including lisinopril and hydrochlorothiazide, significantly reduce cardiovascular morbidity and mortality. The most substantial cardiovascular outcome benefit observed is a reduction in the risk of stroke, alongside reductions in myocardial infarction and overall cardiovascular mortality.

Elevated systolic or diastolic blood pressure is associated with increased cardiovascular risk, and even modest reductions in severe hypertension can yield considerable health benefits. The relative risk reduction from lowering blood pressure is consistent across different populations, with patients at higher baseline risk—such as those with diabetes or hyperlipidemia—experiencing greater absolute benefits.

It is also noted that some antihypertensive medications may exhibit diminished blood pressure-lowering effects when used as monotherapy in black patients. Additionally, many of these agents have other approved indications and therapeutic effects, including those related to angina, heart failure, or diabetic kidney disease.

Dosage and Administration

Lisinopril monotherapy is indicated at once-daily doses ranging from 10 mg to 80 mg. Hydrochlorothiazide monotherapy is effective at daily doses between 12.5 mg and 50 mg.

For patients requiring combination therapy with lisinopril and hydrochlorothiazide, the recommended dosing ranges for lisinopril are 10 mg to 80 mg, while hydrochlorothiazide should be administered at doses of 6.25 mg to 50 mg. In cases where a patient's blood pressure remains inadequately controlled with either monotherapy, a transition to combination therapy with Lisinopril/HCTZ 10/12.5 or Lisinopril/HCTZ 20/12.5 may be appropriate, depending on the current monotherapy dosage.

Adjustments to the dosage of either component should be guided by clinical response, with blood pressure measurements taken at the interdosing interval. It is advised that the hydrochlorothiazide dose not be increased until a period of 2 to 3 weeks has elapsed following initiation of therapy.

Upon the addition of hydrochlorothiazide, it may be feasible to reduce the dose of lisinopril. If discontinuation of the diuretic is not possible, an initial dose of 5 mg of lisinopril should be administered under medical supervision, with monitoring for at least two hours until blood pressure stabilizes for an additional hour.

Contraindications

Lisinopril and hydrochlorothiazide is contraindicated in patients with hypersensitivity to this product. It is also contraindicated in individuals with a history of angioedema associated with prior treatment using an angiotensin-converting enzyme inhibitor, as well as in those with hereditary or idiopathic angioedema.

The hydrochlorothiazide component renders this product contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Additionally, the use of Lisinopril and hydrochlorothiazide is contraindicated in combination with neprilysin inhibitors, such as sacubitril; administration should not occur within 36 hours of switching to or from sacubitril/valsartan.

Furthermore, co-administration of aliskiren with lisinopril and hydrochlorothiazide is contraindicated in patients with diabetes.

Warnings and Precautions

Patients receiving ACE inhibitors, including lisinopril and hydrochlorothiazide, may experience a range of adverse reactions, some of which can be serious.

Anaphylactoid and Angioedema Reactions Anaphylactoid reactions, including angioedema affecting the face, extremities, lips, tongue, glottis, and/or larynx, have been reported in patients treated with ACE inhibitors. These reactions can occur at any time during treatment. In the event of angioedema, lisinopril and hydrochlorothiazide should be discontinued immediately, and appropriate therapy and monitoring should be initiated until complete resolution of symptoms is achieved. It is important to note that fatalities have been reported due to angioedema associated with laryngeal or tongue edema. Additionally, intestinal angioedema has been documented, with symptoms resolving upon cessation of the ACE inhibitor.

Desensitization and Membrane Exposure Risks Life-threatening anaphylactoid reactions may occur in patients undergoing desensitization treatment with hymenoptera venom while receiving ACE inhibitors. Furthermore, sudden and potentially life-threatening anaphylactoid reactions have been observed in patients undergoing dialysis with high-flux membranes while concurrently treated with an ACE inhibitor.

Hypotension and Related Effects Excessive hypotension may result from the use of lisinopril, particularly in patients who are salt or volume-depleted. Therefore, therapy should be initiated under close medical supervision in patients with severe congestive heart failure.

Hematological Monitoring Leukopenia, neutropenia, and agranulocytosis have been associated with ACE inhibitor therapy. Periodic monitoring of white blood cell counts is recommended for patients with collagen vascular disease and renal disease.

Hepatic Considerations Patients receiving ACE inhibitors who develop jaundice or significant elevations in hepatic enzymes should discontinue the medication and seek appropriate medical follow-up.

Fetal Toxicity The use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy is associated with reduced fetal renal function and increased morbidity and mortality in both the fetus and neonate.

General Precautions Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at an increased risk for angioedema while receiving these medications. Additionally, coadministration of ACE inhibitors with mTOR inhibitors or neprilysin inhibitors may heighten the risk of angioedema. Thiazide-containing combination products should be avoided in patients with severe renal dysfunction.

Laboratory Monitoring Regular monitoring of white blood cell counts is advisable for patients with collagen vascular disease and renal disease to detect potential hematological complications early.

Emergency Medical Assistance In cases where angioedema involves the tongue, glottis, or larynx, potentially leading to airway obstruction, immediate administration of subcutaneous epinephrine solution (1:1000, 0.3 mL to 0.5 mL) and measures to ensure airway patency are critical.

Discontinuation and Medical Consultation Patients receiving ACE inhibitors who experience jaundice or marked elevations in hepatic enzymes should discontinue the medication and consult their healthcare provider for further evaluation and management.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions observed in clinical trials include dizziness (7.5%, with 0.8% leading to discontinuation), headache (5.2%, with 0.3% discontinuation), and cough (3.9%, with 0.6% discontinuation). Other frequently reported reactions include fatigue (3.7%, 0.4% discontinuation), orthostatic effects (3.2%, 0.1% discontinuation), diarrhea (2.5%, 0.2% discontinuation), and nausea (2.2%, 0.1% discontinuation). Additionally, upper respiratory infections and muscle cramps were reported in 2.2% and 2.0% of patients, respectively, with discontinuation rates of 0.0% and 0.4%. Other common reactions include asthenia (1.8%, 0.2% discontinuation), paresthesia (1.5%, 0.1% discontinuation), hypotension (1.4%, 0.3% discontinuation), vomiting (1.4%, 0.1% discontinuation), dyspepsia (1.3%, 0.0% discontinuation), rash (1.2%, 0.1% discontinuation), and impotence (1.2%, 0.3% discontinuation).

In addition to these common reactions, other adverse effects have been reported across various body systems. Patients may experience chest pain, abdominal pain, syncope, and chest discomfort. Cardiovascular effects may include palpitations and orthostatic hypotension. Gastrointestinal symptoms can encompass gastrointestinal cramps, dry mouth, constipation, and heartburn. Musculoskeletal complaints such as back pain, shoulder pain, and myalgia have also been noted. Nervous system and psychiatric effects include decreased libido, vertigo, depression, and somnolence. Respiratory issues may manifest as common cold, nasal congestion, and dyspnea, among others. Skin reactions can include flushing, pruritus, and skin inflammation. Special senses may be affected, leading to blurred vision and tinnitus, while urogenital issues such as urinary tract infections have also been reported.

Warnings associated with treatment include the risk of angioedema, which may affect the face, extremities, lips, tongue, glottis, and/or larynx. Rare cases of intestinal angioedema have been reported in postmarketing experience. Hypotension-related adverse effects were observed in clinical trials, with hypotension occurring in 1.4% of patients, orthostatic hypotension in 0.5%, and syncope in 0.8%. A persistent nonproductive cough has been noted with all ACE inhibitors, typically resolving after discontinuation of therapy.

Postmarketing experience has indicated an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC), in white patients receiving large cumulative doses of hydrochlorothiazide.

Drug Interactions

Patients receiving lisinopril should be aware of several important drug interactions that may affect their treatment outcomes and safety.

Pharmacodynamic Interactions:

• Diuretics: The initiation of lisinopril in patients on diuretics may lead to hypotension. It is advisable to consider discontinuing the diuretic or increasing salt intake prior to starting lisinopril to mitigate this risk.

• NSAIDs: Co-administration of non-steroidal anti-inflammatory drugs (NSAIDs) with lisinopril can result in renal function deterioration, particularly in elderly or volume-depleted patients. Additionally, the antihypertensive effect of lisinopril may be diminished by NSAIDs.

• Dual RAS Blockade: The use of lisinopril in conjunction with other agents that block the renin-angiotensin system (RAS) can heighten the risks of hypotension, hyperkalemia, and alterations in renal function.

• Neprilysin Inhibitors: Patients taking neprilysin inhibitors alongside lisinopril may face an increased risk of angioedema.

• mTOR Inhibitors: The combination of ACE inhibitors, such as lisinopril, with mTOR inhibitors (e.g., temsirolimus) may elevate the risk of angioedema.

Pharmacokinetic Interactions:

• Aliskiren: The combination of aliskiren with lisinopril and hydrochlorothiazide is contraindicated in patients with diabetes or renal impairment (GFR < 60 mL/min).

• Potassium-Sparing Diuretics and Supplements: Lisinopril may increase serum potassium levels when used with potassium-sparing diuretics or potassium supplements; therefore, monitoring of serum potassium levels is recommended.

• Lithium: The concurrent use of lithium with lisinopril can lead to lithium toxicity; frequent monitoring of serum lithium levels is advised.

Hydrochlorothiazide Interactions:

• Alcohol, Barbiturates, and Narcotics: The use of hydrochlorothiazide with alcohol, barbiturates, or narcotics may enhance the risk of orthostatic hypotension.

• Antidiabetic Drugs: Dosage adjustments of antidiabetic medications may be necessary when used in conjunction with hydrochlorothiazide.

• Other Antihypertensives: The use of other antihypertensive agents with hydrochlorothiazide may result in additive effects.

• Cholestyramine and Colestipol Resins: These resins can significantly impair the absorption of hydrochlorothiazide, potentially reducing its efficacy.

• Corticosteroids: The use of corticosteroids may exacerbate electrolyte depletion, particularly hypokalemia, when administered with hydrochlorothiazide.

• Lithium and Diuretics: Lithium should generally be avoided in patients taking diuretics due to the increased risk of lithium toxicity.

• NSAIDs and Thiazide Diuretics: Non-steroidal anti-inflammatory drugs may diminish the effectiveness of thiazide diuretics, including hydrochlorothiazide.

Injectable Gold: Nitritoid reactions have been reported in patients receiving injectable gold in combination with ACE inhibitors like lisinopril and hydrochlorothiazide.

Monitoring and appropriate dosage adjustments are essential when managing patients on these medications to ensure safety and therapeutic efficacy.

Packaging & NDC

The table below lists all NDC Code configurations of Lisinopril 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 lisinopril 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 to manage impaired renal function. Lisinopril, which is known to cross the placenta, has been effectively removed from neonatal circulation through peritoneal dialysis, demonstrating some clinical benefit. Although theoretically, exchange transfusion could also facilitate removal, there is currently no clinical experience to support this procedure.

It is important to note that the safety and effectiveness of this medication in pediatric patients have not been established. Therefore, caution is advised when considering its use in this population.

Geriatric Use

Elderly patients, defined as those aged 65 and older, were not adequately represented in clinical studies of lisinopril and hydrochlorothiazide, making it difficult to ascertain whether they respond differently compared to younger patients. However, available clinical experience has not indicated any significant differences in responses between these age groups.

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 medications. Given that this drug is primarily excreted by the kidneys, there is an elevated risk of toxic reactions in patients with impaired renal function.

Therefore, careful consideration must be given to dose adjustments in elderly patients, particularly due to their higher propensity for renal impairment. It is essential that the evaluation of hypertensive elderly patients includes a thorough assessment of renal function to ensure safe and effective treatment.

Pregnancy

When pregnancy is detected, lisinopril and hydrochlorothiazide should be discontinued as soon as possible due to the risk of fetal toxicity. Drugs that act directly on the renin-angiotensin system, including lisinopril and hydrochlorothiazide, can cause significant injury and death to the developing fetus. The use of these medications during the second and third trimesters is particularly concerning, as they can reduce fetal renal function, leading to increased morbidity and mortality in both the fetus and neonate.

Oligohydramnios, a potential consequence of such drug use, may result in fetal lung hypoplasia and skeletal deformations. Neonatal adverse effects associated with in utero exposure include skull hypoplasia, anuria, hypotension, renal failure, and death. While most epidemiologic studies examining fetal abnormalities after antihypertensive exposure in the first trimester have not specifically distinguished between drugs affecting the renin-angiotensin system and other antihypertensive agents, the risks associated with these medications are well-documented.

Appropriate management of maternal hypertension during pregnancy is crucial to optimize outcomes for both mother and fetus. In cases where there is no suitable alternative to therapy with renin-angiotensin system-affecting drugs, healthcare providers should inform the mother of the potential risks to the fetus. Serial ultrasound examinations are recommended to assess the intra-amniotic environment, and if oligohydramnios is detected, lisinopril and hydrochlorothiazide should be discontinued unless deemed lifesaving for the mother.

Fetal testing may be warranted based on the gestational age, and it is important for patients and healthcare providers to recognize that oligohydramnios may not manifest until after the fetus has sustained irreversible injury. Infants with a history of in utero exposure to lisinopril and hydrochlorothiazide should be closely monitored for hypotension, oliguria, and hyperkalemia.

Teratogenicity studies conducted in pregnant rats, mice, and rabbits have not demonstrated teratogenic effects associated with lisinopril. However, in rats, decreased maternal weight gain and fetal weight were observed at doses as low as 3/10 mg/kg/day. It is critical to note that the use of ACE inhibitors during the second and third trimesters can lead to severe fetal injury and even death.

Lactation

It is not known whether lisinopril is excreted in human milk. However, studies in lactating rats have shown that the milk contains radioactivity following the administration of 14C lisinopril, and lisinopril was present in rat milk at levels similar to plasma levels in the dams. Thiazides, which are components of this medication, do appear in human milk.

Due to the potential for serious adverse reactions in breastfed infants from ACE inhibitors and hydrochlorothiazide, healthcare professionals should consider the importance of lisinopril and hydrochlorothiazide to the mother when making decisions regarding the continuation of nursing or the discontinuation of the medication.

Renal Impairment

Thiazide-containing combination products are not recommended for patients with severe renal dysfunction due to the risk of precipitating azotemia and the potential for cumulative effects of the drug in those with impaired renal function. In patients with renal disease, periodic monitoring of white blood cell counts should be considered, particularly in individuals with collagen vascular disease.

Excessive hypotension has been observed in patients with severe congestive heart failure, regardless of the presence of renal insufficiency, and may lead to oliguria, progressive azotemia, and, in rare cases, acute renal failure or death. Patients receiving ACE inhibitors, including lisinopril and hydrochlorothiazide, may experience a range of adverse reactions, some of which can be serious, especially in those with renal impairment.

Additionally, patients with a history of angioedema unrelated to ACE-inhibitor therapy may have an increased risk of angioedema while on an ACE inhibitor. In cases of severe renal dysfunction, if anaphylactoid reactions occur, dialysis must be stopped immediately, and aggressive therapy for such reactions should be initiated.

Hepatic Impairment

Patients with hepatic impairment may experience an increased risk of adverse effects when treated with ACE inhibitors. Rarely, these medications have been associated with a syndrome that begins with cholestatic jaundice or hepatitis and can progress to fulminant hepatic necrosis, which may result in death. The underlying mechanism of this syndrome remains unclear.

In patients receiving ACE inhibitors, if jaundice or significant elevations in hepatic enzymes are observed, it is imperative to discontinue the ACE inhibitor immediately and ensure appropriate medical follow-up is provided.

Thiazide diuretics should be administered with caution in patients with impaired hepatic function or those with progressive liver disease. Minor alterations in fluid and electrolyte balance in these patients may precipitate hepatic coma, necessitating careful monitoring and potential dosage adjustments.

Overdosage

In cases of overdosage with lisinopril and hydrochlorothiazide, specific treatment protocols are not well established. Management is primarily symptomatic and supportive, necessitating the discontinuation of the medication and close observation of the patient.

Recommended Actions

For suspected overdose, the following measures are suggested:

• Induction of emesis and/or gastric lavage may be considered to reduce the absorption of the drugs.

• It is essential to correct any dehydration, electrolyte imbalances, and hypotension using established medical procedures.

Potential Symptoms

The most likely manifestation of lisinopril overdosage is hypotension. In animal studies, a single oral dose of 20 g/kg of lisinopril did not result in lethality; however, hypotension was observed. This condition can be managed effectively with intravenous infusion of normal saline solution.

In the case of hydrochlorothiazide, a single oral dose of 10 g/kg administered to mice and rats was also non-lethal. Common signs and symptoms associated with hydrochlorothiazide overdosage include electrolyte depletion, specifically hypokalemia, hypochloremia, and hyponatremia, as well as dehydration resulting from excessive diuresis.

Additional Management Considerations

Lisinopril can be effectively removed from the bloodstream through hemodialysis, which may be beneficial in severe cases of overdose. Continuous monitoring and supportive care are critical in managing the patient's condition until stabilization is achieved.

Nonclinical Toxicology

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with reduced fetal renal function, leading to increased fetal and neonatal morbidity and mortality. Oligohydramnios resulting from such drug use can contribute to fetal lung hypoplasia and skeletal deformations. Potential adverse neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death. It is recommended to discontinue lisinopril and hydrochlorothiazide as soon as pregnancy is detected, particularly due to the risks associated with their use during the later stages of pregnancy. Most epidemiologic studies investigating fetal abnormalities following antihypertensive exposure in the first trimester have not differentiated between drugs affecting the renin-angiotensin system and other antihypertensive agents.

In nonclinical studies, no teratogenic effects of lisinopril were observed in pregnant rats, mice, and rabbits, with doses administered being up to 625 times (in mice), 188 times (in rats), and 0.6 times (in rabbits) the maximum recommended human dose on a mg/kg basis. Teratogenicity studies conducted in mice and rats with doses of lisinopril up to 90 mg/kg/day (56 times the maximum recommended human dose) in combination with hydrochlorothiazide at 10 mg/kg/day (2.5 times the maximum recommended human dose) did not reveal maternal or fetotoxic effects in mice. However, in rats, decreased maternal weight gain and fetal weight were observed at doses as low as 3/10 mg/kg/day, which were associated with delays in fetal ossification. These effects were not present in saline-supplemented animals receiving the combination of 90/10 mg/kg/day.

Non-teratogenic effects may include fetal or neonatal jaundice, thrombocytopenia, and potentially other adverse reactions observed in adults.

Lisinopril in combination with hydrochlorothiazide was not found to be mutagenic in microbial mutagen tests using Salmonella typhimurium (Ames test) or Escherichia coli, both with and without metabolic activation, nor in a forward mutation assay using Chinese hamster lung cells. Additionally, no DNA single strand breaks were produced in an in vitro alkaline elution assay using rat hepatocytes, and no increases in chromosomal aberrations were observed in either an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow.

There was no evidence of tumorigenic effects when lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg/kg/day (approximately 56 or 9 times the maximum daily human dose, based on body weight and body surface area, respectively). Similarly, no evidence of carcinogenicity was found when lisinopril was administered for 92 weeks to male and female mice at doses up to 135 mg/kg/day (about 84 times the maximum recommended daily human dose), which corresponds to 6.8 times the maximum human dose based on body surface area in mice.

Studies in rats indicate that lisinopril poorly crosses the blood-brain barrier, and multiple doses do not result in tissue accumulation. However, the milk of lactating rats contains radioactivity following administration of 14C-lisinopril. Whole body autoradiography revealed radioactivity in the placenta of pregnant rats after administration of the labeled drug, but no radioactivity was detected in the fetuses.

Postmarketing Experience

Hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC). Data derived from a study conducted within the Sentinel System indicate that this increased risk is predominantly observed in white patients who are administered large cumulative doses of the medication. Specifically, the overall population exhibits an approximate risk increase of 1 additional case of SCC per 16,000 patients per year. In contrast, white patients receiving a cumulative dose of ≥50,000 mg demonstrate a significantly higher risk, with an estimated 1 additional case of SCC for every 6,700 patients per year.

Patient Counseling

Patients should be advised to report immediately any signs or symptoms suggesting angioedema, which may include swelling of the face, extremities, eyes, lips, or tongue, as well as difficulty in swallowing or breathing. They should be instructed to refrain from taking any additional doses of the medication until they have consulted with their prescribing physician.

Patients should be cautioned to report any instances of lightheadedness, particularly during the initial days of therapy. In the event of actual syncope, patients should be advised to discontinue the medication and seek guidance from their prescribing physician.

It is important to inform all patients that excessive perspiration and dehydration can lead to a significant drop in blood pressure due to reduced fluid volume. They should also be made aware that other factors contributing to volume depletion, such as vomiting or diarrhea, may similarly result in a decrease in blood pressure. Patients are encouraged to consult with their physician if they experience these conditions.

Patients should be instructed not to use salt substitutes that contain potassium without prior consultation with their physician.

Prompt reporting of any signs of infection, such as a sore throat or fever, is essential, as these may indicate leukopenia or neutropenia. Patients should be made aware of this potential risk.

Female patients of childbearing age should be informed about the implications of exposure to lisinopril and hydrochlorothiazide during pregnancy. It is crucial to discuss 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 taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and to undergo regular skin cancer screenings to monitor for any potential issues.

Storage and Handling

The product is supplied in accordance with the following specifications: it should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. It is essential to protect the product from excessive light and humidity to maintain its integrity and efficacy.

Additional Clinical Information

Periodic determination of serum electrolytes is recommended to detect potential electrolyte imbalances in patients, particularly those undergoing treatment with thiazides, which can increase urinary magnesium excretion and lead to hypomagnesemia. Clinicians should assess renal function in hypertensive patients and consider serum and urine electrolyte evaluations, especially in cases of excessive vomiting or parenteral fluid administration. It is advised to discontinue thiazides prior to conducting parathyroid function tests.

Patient counseling is essential, with emphasis on reporting any signs of angioedema, such as facial or extremity swelling and difficulty breathing, before continuing medication. Patients should be made aware of the risk of lightheadedness, particularly during the initial days of therapy, and advised to discontinue use if syncope occurs until consulting their physician. Caution should be exercised regarding excessive perspiration, dehydration, and other causes of volume depletion that may lead to hypotension. Patients are also advised against using potassium-containing salt substitutes without medical consultation and should promptly report any signs of infection, which may indicate leukopenia or neutropenia. Female patients of childbearing age should discuss the implications of treatment during pregnancy with their healthcare provider and report any pregnancies immediately. Additionally, those taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and to undergo regular skin cancer screenings.

FDA Insert (PDF)

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

View full prescribing information (PDF)