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. 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 includes 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 effectively lower blood pressure. The reduction of blood pressure is associated with a decreased risk of both fatal and non-fatal cardiovascular events, particularly strokes and myocardial infarctions.

Management of high blood pressure 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 targets.

Clinical evidence from randomized controlled trials has demonstrated that various antihypertensive agents can significantly reduce cardiovascular morbidity and mortality, with blood pressure reduction being a key factor in these outcomes. The most substantial cardiovascular 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 linked to increased cardiovascular risk, and even modest reductions in severe hypertension can yield considerable health benefits. The relative risk reduction associated with blood pressure lowering 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 certain antihypertensive medications may exhibit diminished blood pressure-lowering effects when used as monotherapy in black patients. Additionally, many of these agents may 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 is lisinopril at 10 mg to 80 mg and hydrochlorothiazide at 6.25 mg to 50 mg. In cases where a patient's blood pressure remains inadequately controlled with either monotherapy, a transition to a combination of lisinopril/HCTZ 10/12.5 or lisinopril/HCTZ 20/12.5 may be appropriate, based 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 to assess the patient's response adequately.

In situations where the diuretic cannot be discontinued, an initial dose of 5 mg of lisinopril should be administered under medical supervision. Blood pressure should be monitored for at least two hours following administration, ensuring stabilization for an additional hour before any further adjustments are made.

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 previous treatment using an angiotensin-converting enzyme inhibitor, as well as in those with hereditary or idiopathic angioedema.

The hydrochlorothiazide component contraindicates use in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Additionally, this product should not be used in combination with a neprilysin inhibitor, such as sacubitril; administration of Lisinopril and Hydrochlorothiazide tablets USP should be avoided within 36 hours of switching to or from sacubitril/valsartan.

Co-administration of aliskiren with lisinopril and hydrochlorothiazide is contraindicated in patients with diabetes.

Warnings and Precautions

Patients receiving ACE inhibitors, including lisinopril, may experience a range of serious adverse reactions, necessitating careful monitoring and management.

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 therapy. In cases of angioedema, lisinopril should be discontinued immediately, and appropriate therapy and monitoring should be initiated until complete resolution of symptoms. Fatalities have been documented due to angioedema associated with laryngeal or tongue edema. Additionally, intestinal angioedema may present with abdominal pain, which can occur without prior facial angioedema.

Desensitization and Membrane Exposure Risks Life-threatening anaphylactoid reactions have been observed in patients undergoing desensitization while on ACE inhibitors. Furthermore, patients undergoing dialysis with high-flux membranes while receiving ACE inhibitors may experience sudden and potentially life-threatening anaphylactoid reactions.

Hypotension and Related Effects Excessive hypotension may occur in patients who are salt or volume-depleted. Therefore, therapy should be initiated under close medical supervision, particularly in patients with severe congestive heart failure. In the event of hypotension, the patient should be placed in a supine position and may require intravenous infusion of normal saline.

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 to detect any hematological abnormalities early.

Hepatic Considerations Patients who develop jaundice or significant elevations in hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up to assess liver function.

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, these medications should be avoided in pregnant patients during this period.

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 further elevate the risk of angioedema. Patients with renal disease should be monitored closely for cumulative effects when using thiazides.

Emergency Medical Help In cases where angioedema involves the tongue, glottis, or larynx, which may lead to airway obstruction, immediate administration of subcutaneous epinephrine solution (1:1000, 0.3 mL to 0.5 mL) and measures to ensure a patent airway are critical.

Monitoring Recommendations Regular monitoring of white blood cell counts is advised for patients with collagen vascular disease and renal disease to ensure early detection of potential complications.

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%, 0.3% discontinuation), cough (3.9%, 0.6% discontinuation), and fatigue (3.7%, 0.4% discontinuation). Other frequently reported reactions include orthostatic effects (3.2%, 0.1% discontinuation), diarrhea (2.5%, 0.2% discontinuation), nausea (2.2%, 0.1% discontinuation), and upper respiratory infections (2.2%, 0.0% discontinuation). Muscle cramps (2.0%, 0.4% discontinuation), asthenia (1.8%, 0.2% discontinuation), and paresthesia (1.5%, 0.1% discontinuation) were also noted, along with 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 events have been reported. These include chest pain, abdominal pain, syncope, and chest discomfort under the category of body as a whole. Cardiovascular effects may include palpitations and orthostatic hypotension. Digestive system reactions can involve gastrointestinal cramps, dry mouth, constipation, and heartburn. Musculoskeletal complaints such as back pain, shoulder pain, knee pain, and myalgia have also been documented. Nervous and psychiatric effects include decreased libido, vertigo, depression, and somnolence. Respiratory issues may manifest as common cold, nasal congestion, influenza, bronchitis, and dyspnea. Skin reactions can include flushing, pruritus, and skin inflammation, while special senses may be affected by blurred vision and tinnitus. Urogenital adverse reactions include urinary tract infections.

Warnings associated with treatment include the risk of angioedema, which may affect the face, extremities, lips, tongue, glottis, and/or larynx. Hypotension has been reported in clinical trials, occurring in 1.4% of patients, with orthostatic hypotension noted in 0.5% and other orthostatic effects in 3.2%. Syncope was observed in 0.8% of participants. Additionally, a persistent nonproductive cough has been reported with ACE inhibitors, typically resolving after discontinuation of therapy.

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

Drug Interactions

Patients receiving lisinopril may experience several significant drug interactions that necessitate careful monitoring and potential dosage adjustments.

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

• Aliskiren: In diabetic patients or those with renal impairment (GFR < 60 mL/min), the co-administration of aliskiren with lisinopril is contraindicated.

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

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

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

• Neprilysin Inhibitors: Patients taking neprilysin inhibitors alongside lisinopril may also face an elevated risk for angioedema.

Pharmacokinetic Interactions:

• Hydrochlorothiazide: The use of hydrochlorothiazide with alcohol, barbiturates, or narcotics may enhance the risk of orthostatic hypotension. Antidiabetic medications may require dosage adjustments when used concurrently with hydrochlorothiazide. Additionally, other antihypertensive agents may exhibit additive effects when combined with hydrochlorothiazide.

• Cholestyramine and Colestipol Resins: These resins can significantly impair the absorption of hydrochlorothiazide, necessitating careful consideration of their co-administration.

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

• Lithium and Diuretics: The combination of lithium with diuretics is generally discouraged 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 and ACE Inhibitors: Nitritoid reactions have been reported in patients receiving injectable gold in conjunction with ACE inhibitors like lisinopril and hydrochlorothiazide.

Healthcare providers should remain vigilant for these interactions and consider appropriate monitoring and dosage adjustments as necessary to ensure patient safety.

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 manage 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 treatment 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 elderly and younger patients.

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. Given that this medication is primarily excreted by the kidneys, the risk of adverse reactions may be heightened in patients with impaired renal function.

Therefore, careful consideration should be given to renal function when determining the appropriate dosage for elderly patients. Regular assessment of renal function is essential in the evaluation of hypertensive elderly patients to ensure safe and effective treatment.

Pregnancy

Drugs that act directly on the renin-angiotensin system, including lisinopril and hydrochlorothiazide, carry a warning for potential fetal toxicity. These medications can cause significant injury and even death to the developing fetus, particularly when used during the second and third trimesters of pregnancy. The use of such drugs during these trimesters has been associated with reduced fetal renal function, leading to increased morbidity and mortality in both the fetus and neonate.

When pregnancy is detected, it is imperative to discontinue lisinopril and hydrochlorothiazide as soon as possible. The resulting oligohydramnios from the use of these medications can lead to serious complications, including fetal lung hypoplasia and skeletal deformations. Potential adverse effects in neonates may include skull hypoplasia, anuria, hypotension, renal failure, and death.

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. Therefore, while the teratogenic effects of lisinopril have not been observed in studies involving pregnant rats, mice, and rabbits, caution is warranted. In studies where lisinopril was combined with hydrochlorothiazide, no maternal or fetotoxic effects were noted in mice; however, in rats, decreased maternal weight gain and fetal weight were observed at lower doses, along with delays in fetal ossification.

Appropriate management of maternal hypertension during pregnancy is crucial to optimize outcomes for both the 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 should be performed to monitor the intra-amniotic environment, and if oligohydramnios is detected, discontinuation of the medications should be considered unless deemed lifesaving for the mother. Fetal testing may also be warranted based on gestational age, as 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.

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, with lisinopril present in rat milk at levels similar to plasma levels in the dams. Thiazides, which may be co-administered with lisinopril, are known to 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 risks and benefits when advising lactating mothers. A decision should be made regarding the discontinuation of nursing and/or the discontinuation of lisinopril and hydrochlorothiazide, taking into account the importance of the medication to the mother.

Renal Impairment

Patients with renal impairment should be closely monitored when receiving treatment involving thiazide-containing combination products, as these are not recommended for individuals with severe renal dysfunction. In patients with renal disease, thiazides may precipitate azotemia, and the cumulative effects of the drug can develop in those with impaired renal function.

Periodic monitoring of white blood cell counts is advisable for patients with collagen vascular disease and renal disease. Additionally, excessive hypotension has been observed in patients with severe congestive heart failure, with or without associated renal insufficiency, which may lead to oliguria, progressive azotemia, and, in rare cases, acute renal failure or death.

Patients with a history of angioedema unrelated to ACE-inhibitor therapy may have an increased risk of angioedema while receiving an ACE inhibitor. Those receiving ACE inhibitors, including lisinopril and hydrochlorothiazide, may experience a range of adverse reactions, some of which can be serious due to their effects on renal function.

In patients with hypertension treated with lisinopril alone, the incidence of syncope was reported at 0.1 percent, potentially influenced by renal function. It is essential that patients with renal impairment are followed closely during the first two weeks of treatment and whenever there is an increase in the dose of lisinopril and/or diuretic.

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 established; therefore, management is primarily symptomatic and supportive.

Potential Symptoms and Manifestations The most significant manifestation of lisinopril overdosage is hypotension. This condition should be addressed promptly, typically through the administration of intravenous normal saline solution to restore blood pressure. Additionally, it is important to note that lisinopril can be effectively removed from the system via hemodialysis, which may be considered in severe cases.

In the case of hydrochlorothiazide, studies involving oral administration of a single high dose (10 g/kg) in mice and rats did not result in lethality. However, common adverse effects observed include electrolyte depletion and dehydration, which arise from excessive diuresis.

Considerations with Co-Administration of Digitalis If digitalis has been co-administered, it is crucial to monitor for hypokalemia, as this condition may exacerbate the risk of cardiac arrhythmias. Healthcare professionals should remain vigilant for these potential complications and manage them accordingly.

In summary, the management of overdosage with lisinopril and hydrochlorothiazide requires a supportive approach, with particular attention to blood pressure stabilization and monitoring for electrolyte imbalances.

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 use can contribute to fetal lung hypoplasia and skeletal deformations. Potential adverse neonatal outcomes 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 significantly higher than the maximum recommended human dose. Teratogenicity studies involving mice and rats administered up to 90 mg/kg/day of lisinopril in combination with 10 mg/kg/day of hydrochlorothiazide did not reveal maternal or fetotoxic effects in mice. However, in rats, decreased maternal weight gain and fetal weight were noted at lower doses, accompanied by a delay in fetal ossification. These effects were not observed in saline-supplemented animals receiving the same combination of doses.

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

Lisinopril in combination with hydrochlorothiazide was not found to be mutagenic in microbial mutagen tests using Salmonella typhimurium or Escherichia coli, with or 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 both in vitro tests with Chinese hamster ovary cells and in vivo studies in mouse bone marrow.

Long-term studies indicated no evidence of tumorigenicity when lisinopril was administered to male and female rats for 105 weeks at doses up to 90 mg/kg/day. Similarly, no carcinogenicity was observed in mice administered lisinopril for 92 weeks at doses up to 135 mg/kg/day. Hydrochlorothiazide also demonstrated no genotoxicity in vitro in the Ames mutagenicity assay and in tests for chromosomal aberrations, as well as in vivo assays involving mouse germinal cell chromosomes and Chinese hamster bone marrow chromosomes.

Studies in rats have shown that lisinopril poorly crosses the blood-brain barrier and does not accumulate in tissues following multiple doses. However, radioactivity was detected in the milk of lactating rats after administration of 14C-lisinopril. Whole body autoradiography revealed radioactivity in the placenta of pregnant rats, but none was found in the fetuses.

Postmarketing Experience

Postmarketing experience has identified an association between hydrochlorothiazide and 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 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 more pronounced risk, with an estimated increase of 1 additional SCC case 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 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 decreased 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.

Female patients of childbearing age should be informed about the potential consequences of exposure to lisinopril and hydrochlorothiazide during pregnancy. It is advisable 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.

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. Clinicians should assess renal function in hypertensive patients and consider serum and urine electrolyte evaluations, particularly in cases of excessive vomiting or when patients are receiving parenteral fluids. Thiazide diuretics can increase urinary magnesium excretion, potentially leading to hypomagnesemia, while they may also decrease urinary calcium excretion. It is advised to discontinue thiazides prior to conducting tests for parathyroid function.

Patients should be counseled on several important safety considerations. They must report any signs of angioedema, such as swelling of the face or difficulty breathing, and should not continue the medication without consulting their physician. Lightheadedness, especially during the initial days of therapy, should be reported, and if syncope occurs, the medication should be discontinued until medical advice is obtained. Patients should be aware that excessive perspiration, dehydration, or other causes of volume depletion can lead to significant drops in blood pressure. Additionally, they should avoid potassium-containing salt substitutes without prior consultation. Signs of infection, such as sore throat or fever, should prompt immediate reporting due to the risk of leukopenia or neutropenia. Female patients of childbearing age should be informed about the risks associated with the use of lisinopril and hydrochlorothiazide during pregnancy and should report any pregnancies to their healthcare provider. Finally, those taking hydrochlorothiazide should be advised 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 Lupin Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)