Lisinopril/Hydrochlorothiazide

Description

Lisinopril and hydrochlorothiazide tablet USP is a combination medication that includes lisinopril, an angiotensin converting enzyme (ACE) inhibitor, and hydrochlorothiazide, a diuretic. Lisinopril is a synthetic peptide derivative, chemically designated as (S)-1-N2-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline dihydrate, with an empirical formula of C21H31N3O5 • 2H2O and a molecular weight of 441.53. It appears as a white to off-white crystalline powder, 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. This compound is a white or practically white crystalline powder, slightly soluble in water, and freely soluble in sodium hydroxide solution.

The tablets are formulated for oral administration and are available in three strengths: 10 mg lisinopril and 12.5 mg hydrochlorothiazide, 20 mg lisinopril and 12.5 mg hydrochlorothiazide, and 20 mg lisinopril and 25 mg hydrochlorothiazide. Inactive ingredients include dibasic calcium phosphate, magnesium stearate, mannitol, pregelatinized starch, and corn starch. The 10 mg/12.5 mg formulation contains FD&C Blue No. 2 Aluminum Lake, the 20 mg/12.5 mg formulation includes yellow iron oxide, and the 20 mg/25 mg formulation 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, primarily 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 goals.

Numerous antihypertensive agents have demonstrated efficacy in randomized controlled trials, showing a reduction in cardiovascular morbidity and mortality, with blood pressure reduction being a significant contributor to these benefits. The most substantial and consistent cardiovascular outcome benefit observed is a reduction in the risk of stroke, alongside reductions in myocardial infarction and cardiovascular mortality.

Elevated systolic or diastolic blood pressure is linked to increased cardiovascular risk, with a greater absolute risk increase per mmHg at higher blood pressures. Even modest reductions in severe hypertension can yield considerable benefits. The relative risk reduction associated with blood pressure lowering is consistent across various populations with differing absolute risks, with patients at higher risk—such as those with diabetes or hyperlipidemia—experiencing greater absolute benefits.

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

Dosage and Administration

Lisinopril is indicated for the effective treatment of hypertension as monotherapy in once-daily doses ranging from 10 mg to 80 mg. Hydrochlorothiazide is also effective as monotherapy, with recommended doses between 12.5 mg and 50 mg per day.

For patients requiring combination therapy, lisinopril may be administered in doses of 10 mg to 80 mg alongside hydrochlorothiazide in doses of 6.25 mg to 50 mg. In cases where blood pressure is not adequately controlled, patients may be transitioned to Lisinopril and Hydrochlorothiazide tablets at either 10 mg/12.5 mg or 20 mg/12.5 mg, depending on the current monotherapy dose.

Dose titration should be guided by clinical response, with blood pressure measurements taken at the interdosing interval. It is recommended 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 instances where a diuretic cannot be discontinued, an initial dose of 5 mg of lisinopril should be administered under medical supervision for at least two hours, ensuring that blood pressure has stabilized for an additional hour before further adjustments.

The combination of lisinopril and hydrochlorothiazide may be used as a replacement therapy for the titrated individual components.

For patients with renal impairment, therapy regimens with lisinopril and hydrochlorothiazide tablets do not require adjustments based on renal function, provided that the patient's creatinine clearance is greater than 30 mL/min/1.7 m² (serum creatinine approximately ≤3 mg/dL or 265 µmol/L).

Contraindications

Lisinopril and hydrochlorothiazide is contraindicated in patients with a known 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 patients with hereditary or idiopathic angioedema.

The hydrochlorothiazide component renders this product contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Additionally, 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. These reactions can occur at any time during treatment. In the event of angioedema, it is imperative to discontinue lisinopril and hydrochlorothiazide immediately and provide appropriate therapy and monitoring until the resolution of symptoms. Fatalities have been reported in rare cases due to laryngeal or tongue edema.

Intestinal angioedema has also been documented in patients treated with ACE inhibitors, typically presenting as abdominal pain, with symptoms resolving upon discontinuation of the medication. Additionally, life-threatening anaphylactoid reactions may occur during desensitization treatment or in patients undergoing dialysis with high-flux membranes while on ACE inhibitors.

Hypotension and Related Effects

Excessive hypotension may occur, 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. If hypotension occurs, the patient should be placed in a supine position and may require intravenous infusion of normal saline.

Hematological and Hepatic Concerns

Rare cases of leukopenia, neutropenia, and agranulocytosis have been reported, particularly in patients with collagen vascular disease and renal disease. Periodic monitoring of white blood cell counts is recommended for these patients. Furthermore, ACE inhibitors have been associated with a syndrome that can lead to fulminant hepatic necrosis and death; discontinuation is advised if jaundice or significant elevations in hepatic enzymes are observed.

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.

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. Caution is advised when prescribing thiazides to patients with renal disease, as they may precipitate azotemia, and cumulative effects can develop in those with impaired renal function. Thiazides should also be used cautiously in patients with impaired hepatic function or progressive liver disease. Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma, and there is a reported possibility of exacerbation or activation of systemic lupus erythematosus.

Laboratory Monitoring

Periodic monitoring of white blood cell counts is recommended 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 a patent airway are essential.

Healthcare professionals should remain vigilant for these warnings and precautions to ensure patient safety during treatment with ACE inhibitors.

Side Effects

Patients receiving treatment may experience a range of adverse reactions. The most common adverse reactions, occurring in at least 1% of participants, include dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), and orthostatic effects (3.2%). Other common reactions include diarrhea (2.5%), nausea (2.2%), upper respiratory infection (2.2%), muscle cramps (2.0%), and asthenia (1.8%). Less frequently reported reactions include paresthesia (1.5%), hypotension (1.4%), vomiting (1.4%), dyspepsia (1.3%), rash (1.2%), and impotence (1.2%). Notably, some of these reactions led to discontinuation of treatment, with dizziness and headache being the most significant contributors.

In addition to the common adverse reactions, patients may experience other reactions categorized by body systems. Cardiovascular effects may include palpitations and orthostatic hypotension, while gastrointestinal issues can manifest as gastrointestinal cramps, dry mouth, constipation, and heartburn. Musculoskeletal complaints such as back pain, shoulder pain, and myalgia have also been reported.

Nervous system and psychiatric effects may include decreased libido, vertigo, depression, and somnolence. Respiratory reactions can range from common cold symptoms to more severe conditions such as dyspnea and pulmonary congestion. Skin reactions may include flushing, pruritus, and skin inflammation. Special senses may be affected, with reports of blurred vision and tinnitus. Urogenital issues, such as urinary tract infections, have also been noted.

Serious adverse reactions warrant particular attention. Angioedema, which can affect the face, extremities, lips, tongue, glottis, and/or larynx, has been reported, with rare fatalities associated with laryngeal or tongue edema. Hypotension, including orthostatic hypotension, has been observed in 1.4% of patients, with syncope occurring in 0.8%. Anaphylactoid reactions have been documented, particularly in patients undergoing desensitization. Rare cases of hepatic failure, including cholestatic jaundice and fulminant hepatic necrosis, have also been reported.

Rare adverse reactions include leukopenia, neutropenia, and agranulocytosis, particularly in patients with renal impairment. Intestinal angioedema has been reported in patients treated with ACE inhibitors, presenting with abdominal pain.

Specific reactions associated with hydrochlorothiazide include weakness, anorexia, gastric irritation, jaundice, pancreatitis, and renal dysfunction. Hematologic reactions such as leukopenia and thrombocytopenia have been noted, along with skin reactions including erythema multiforme and exfoliative dermatitis. Hypersensitivity reactions may manifest as purpura, photosensitivity, and respiratory distress, including pneumonitis and pulmonary edema.

Healthcare professionals should monitor patients for these adverse reactions and manage them appropriately.

Drug Interactions

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

Pharmacodynamic Interactions:

• Diuretics: Patients on diuretic therapy may experience excessive hypotension upon initiation of lisinopril. To mitigate this risk, it is advisable to discontinue the diuretic or increase salt intake prior to starting lisinopril.

• Non-Steroidal Anti-Inflammatory Agents (NSAIDs): Co-administration of NSAIDs, including selective COX-2 inhibitors, may lead to renal function deterioration, particularly in elderly patients or those with pre-existing renal impairment. Additionally, the antihypertensive effect of lisinopril may be diminished when used concurrently with NSAIDs.

• Dual Blockade of the Renin-Angiotensin System (RAS): The combination of lisinopril with other agents that block the RAS may increase the risk of hypotension, hyperkalemia, and renal function changes, including acute renal failure.

• Potassium-Increasing Agents: The concomitant use of lisinopril with potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes can lead to significant increases in serum potassium levels.

• Lithium: The use of lisinopril with lithium has been associated with lithium toxicity. Frequent monitoring of serum lithium levels is recommended.

• mTOR Inhibitors: There is an increased risk of angioedema when lisinopril is coadministered with mTOR inhibitors.

Pharmacokinetic Interactions:

• Other Agents: Lisinopril has been used safely with nitrates and/or digoxin without significant adverse interactions. No clinically meaningful pharmacokinetic interactions have been observed with propranolol, digoxin, or hydrochlorothiazide.

For hydrochlorothiazide, several interactions warrant attention:

Pharmacodynamic Interactions:

• Alcohol, Barbiturates, or Narcotics: These substances may potentiate orthostatic hypotension when used with hydrochlorothiazide.

• Antidiabetic Drugs: Dosage adjustments may be necessary for patients taking oral antidiabetic agents or insulin.

• Other Antihypertensive Drugs: The use of hydrochlorothiazide with other antihypertensive medications may result in an additive effect or potentiation of blood pressure-lowering effects.

• Corticosteroids and ACTH: These agents may intensify electrolyte depletion, particularly leading to hypokalemia.

• Pressor Amines (e.g., norepinephrine): There may be a decreased response to pressor amines when used concurrently with hydrochlorothiazide.

• Skeletal Muscle Relaxants (e.g., tubocurarine): Increased responsiveness to nondepolarizing muscle relaxants may occur.

• Lithium: Hydrochlorothiazide can reduce the renal clearance of lithium, increasing the risk of toxicity.

• Non-Steroidal Anti-inflammatory Drugs: The effectiveness of hydrochlorothiazide may be reduced when used with NSAIDs, impacting its diuretic, natriuretic, and antihypertensive effects.

• Gold: Nitritoid reactions have been reported when injectable gold is used in conjunction with ACE inhibitors, including lisinopril.

Healthcare professionals should remain vigilant for these interactions and consider appropriate monitoring and dosage adjustments as necessary.

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

Safety and effectiveness in pediatric patients have not been established. Therefore, the use of this medication in children, infants, and adolescents should be approached with caution, as there is insufficient data to support its use in these populations. Healthcare professionals are advised to consider the potential risks and benefits before prescribing this medication to pediatric patients.

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 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 renal function when selecting doses for elderly patients. Regular assessment of renal function is essential in the evaluation of hypertensive elderly patients to ensure safe and effective treatment.

Pregnancy

Lisinopril crosses the placenta, and its use during pregnancy may pose risks to the fetus. In neonates with a history of in utero exposure to lisinopril and hydrochlorothiazide, the occurrence of oliguria or hypotension necessitates immediate attention to support blood pressure and renal perfusion. In such cases, exchange transfusions or dialysis may be required to address hypotension and/or to manage disordered renal function. Clinical experience indicates that peritoneal dialysis has been effective in removing lisinopril from neonatal circulation, although there is no established experience with exchange transfusion for this purpose.

The safety of lisinopril during lactation is not well established, as it is unknown whether lisinopril is secreted in human milk. However, studies in lactating rats have shown that the milk contains radioactivity following administration of C-14 lisinopril, with levels in rat milk being comparable to plasma levels in the dams. Thiazides, which are also components of the combination therapy, are known to appear in human milk. Given the potential for serious reactions in nursing infants from ACE inhibitors and hydrochlorothiazide, healthcare providers should carefully consider whether to discontinue nursing or to discontinue lisinopril and hydrochlorothiazide, weighing the importance of the medication to the mother against the potential risks to the infant.

Lactation

There is no specific information available regarding the use of this medication in nursing mothers or its effects on lactation. Consequently, the potential for excretion in breast milk and the impact on breastfed infants remain undetermined. Healthcare professionals should exercise caution and consider the lack of data when advising lactating mothers on the use of this medication.

Renal Impairment

Thiazide-containing combination products are not recommended for patients with severe renal dysfunction. In patients with severe congestive heart failure, with or without associated renal insufficiency, excessive hypotension has been observed, which may lead to oliguria, progressive azotemia, and, in rare cases, acute renal failure or death.

Thiazides should be used with caution in patients with severe renal disease, as they may precipitate azotemia. The cumulative effects of the drug can develop in patients with impaired renal function. Additionally, periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease is advisable. Caution is also warranted when administering thiazides to patients with impaired hepatic function or progressive liver disease, as minor alterations in fluid and electrolyte balance may precipitate hepatic coma.

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 management.

Overdosage

In cases of overdosage with lisinopril and hydrochlorothiazide, specific treatment information is limited. Management is primarily symptomatic and supportive. It is recommended that therapy with lisinopril and hydrochlorothiazide be discontinued, and the patient should be closely monitored. Suggested interventions include the induction of emesis and/or gastric lavage, along with the correction of dehydration, electrolyte imbalances, and hypotension through established medical procedures.

The most likely manifestation of overdosage is hypotension. In such instances, the standard treatment involves the intravenous infusion of normal saline solution. Animal studies indicate that a single oral dose of 20 mg/kg did not result in lethality in rats, while one out of twenty mice receiving the same dose did not survive. Furthermore, a single oral dose of 10 mg/kg administered to mice and rats was also non-lethal. The predominant signs and symptoms associated with overdosage are typically those resulting from electrolyte depletion, including hypokalemia, hypochloremia, and hyponatremia, as well as dehydration due to excessive diuresis. It is important to note that if digitalis has been co-administered, hypokalemia may exacerbate the risk of cardiac arrhythmias.

For patients experiencing severe overdosage, hemodialysis may be utilized to facilitate the removal of lisinopril from the system. Continuous monitoring and supportive care are essential to manage the patient's condition effectively.

Nonclinical Toxicology

No teratogenic effects were reported in the studies. Additionally, there were no adverse effects on reproductive performance in male and female rats treated with up to 300 mg/kg/day of lisinopril. Hydrochlorothiazide also demonstrated no adverse effects on the fertility of mice and rats of either sex when these species were exposed, via their diet, to doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to conception and throughout gestation.

Lisinopril in combination with hydrochlorothiazide was not mutagenic in a microbial mutagen test 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. Furthermore, neither lisinopril nor hydrochlorothiazide produced DNA single strand breaks in an in vitro alkaline elution rat hepatocyte assay. Lisinopril did not induce increases in chromosomal aberrations in an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow.

There was no evidence of a tumorigenic effect when lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg/kg/day. Similarly, no evidence of carcinogenicity was observed when lisinopril was administered for 92 weeks to male and female mice at doses up to 135 mg/kg/day. Two-year feeding studies in mice and rats revealed no evidence of carcinogenic potential for hydrochlorothiazide in female mice or in male and female rats. However, the National Toxicology Program (NTP) found equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays.

Postmarketing Experience

Postmarketing experience has identified several adverse events reported voluntarily or through surveillance programs.

Angioedema affecting the face, extremities, lips, tongue, glottis, and/or larynx has been documented in patients treated with angiotensin-converting enzyme (ACE) inhibitors, including lisinopril. This condition may arise at any point during treatment, with a noted higher incidence in black patients compared to nonblack patients. Additionally, intestinal angioedema has been reported, presenting with abdominal pain (with or without nausea or vomiting). In some instances, patients had no 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 procedures, with symptom resolution following the discontinuation of the ACE inhibitor.

Rare cases of leukopenia/neutropenia and bone marrow depression have been observed, although a causal relationship with lisinopril cannot be definitively established. It is advisable to consider periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease. Furthermore, ACE inhibitors have been infrequently associated with a syndrome that begins with cholestatic jaundice or hepatitis and may progress to fulminant hepatic necrosis, occasionally resulting in death. The underlying mechanism of this syndrome remains unclear, and patients developing jaundice or significant elevations in hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Adverse experiences reported have been consistent with those previously documented for lisinopril or hydrochlorothiazide. In controlled trials, the most frequent clinical adverse experiences associated with any combination of lisinopril and hydrochlorothiazide included dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), and orthostatic effects (3.2%), all occurring more frequently than in placebo-treated patients. Discontinuation of therapy due to adverse effects was necessary in 4.4% of patients, primarily due to dizziness, cough, fatigue, and muscle cramps.

Clinical adverse experiences occurring in more than 1% of patients treated with lisinopril plus hydrochlorothiazide in controlled clinical trials included dizziness, headache, cough, fatigue, orthostatic effects, diarrhea, nausea, upper respiratory infection, muscle cramps, asthenia, paresthesia, hypotension, vomiting, dyspepsia, rash, and impotence. Adverse effects related to hypotension were reported as follows: hypotension (1.4%), orthostatic hypotension (0.5%), and other orthostatic effects (3.2%). Additionally, syncope was observed in 0.8% of patients.

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.

All patients should be informed 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.

Patients must be advised to report any signs of infection, such as a sore throat or fever, promptly, 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 important to discuss treatment options with women who are planning to become pregnant. Patients should be encouraged to report any pregnancies to their physicians as soon as possible.

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 imbalances, particularly in patients experiencing excessive vomiting or receiving parenteral fluids. Minor reversible increases in blood urea nitrogen and serum creatinine have been noted in patients with essential hypertension treated with lisinopril and hydrochlorothiazide. Additionally, small decreases in hemoglobin and hematocrit were frequently observed, though they were rarely clinically significant unless accompanied by other causes of anemia. Rare instances of elevated liver enzymes and/or serum bilirubin have also been reported.

Patients should be counseled to report any signs of angioedema, such as swelling of the face, extremities, or difficulty breathing, and to refrain from taking additional medication until consulting their physician. They should be advised to report lightheadedness, particularly during the initial days of therapy, and to discontinue the drug if syncope occurs. Caution is advised against using potassium-containing salt substitutes without physician consultation. Prompt reporting of any signs of infection, such as sore throat or fever, is essential due to the risk of leukopenia/neutropenia. Female patients of childbearing age should be informed about the risks associated with lisinopril and hydrochlorothiazide during pregnancy and should discuss treatment options with their healthcare provider. Postmarketing experience has documented cases of angioedema affecting various body parts, including rare occurrences of intestinal angioedema.

FDA Insert (PDF)

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

View full prescribing information (PDF)