Hydrochlorothiazide/Lisinopril

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, 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 combinations: 10 mg of lisinopril with 12.5 mg of hydrochlorothiazide; 20 mg of lisinopril with 12.5 mg of hydrochlorothiazide; and 20 mg of lisinopril with 25 mg of 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, 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 goals.

Clinical evidence from randomized controlled trials has demonstrated that numerous antihypertensive agents can reduce 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, and 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, regardless of their hypertension status.

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 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 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 the 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.

Following 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 presence of hydrochlorothiazide necessitates contraindication in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Additionally, the combination of lisinopril and hydrochlorothiazide with a neprilysin inhibitor, such as sacubitril, is contraindicated. Administration of Lisinopril and Hydrochlorothiazide tablets USP should not occur within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor.

Furthermore, 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 adverse reactions, some of which can be serious.

Anaphylactoid and Angioedema Reactions Anaphylactoid reactions, including angioedema of 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 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 has been observed, presenting with abdominal pain, which resolved upon discontinuation of the ACE inhibitor.

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

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

Hematological Considerations Rare cases of leukopenia, neutropenia, and agranulocytosis have been reported. It is advisable to consider periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease.

Hepatic Concerns ACE inhibitors have been associated with a syndrome that can progress to fulminant hepatic necrosis and death. Discontinuation of the medication is warranted if jaundice or significant elevations in hepatic enzymes are observed.

Fetal Toxicity The use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy may impair fetal renal function and increase the risk of morbidity and mortality.

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

Emergency Medical Help In cases where there is involvement of the tongue, glottis, or larynx that 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 should be provided.

Monitoring Recommendations Periodic monitoring of white blood cell counts is recommended for patients with collagen vascular disease and renal disease to detect any potential hematological complications early.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. The most common adverse reactions, occurring in more than 1% of participants, 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 common 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). Additional reactions reported include muscle cramps (2.0%, 0.4% discontinuation), 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).

Serious adverse reactions may include angioedema, which has been reported affecting the face, extremities, lips, tongue, glottis, and/or larynx. Rare cases of intestinal angioedema have also been noted in post-marketing experiences. Hypotension was observed in 1.4% of patients during clinical trials, with syncope occurring in 0.8% of patients. Additionally, a persistent nonproductive cough has been associated with the use of ACE inhibitors, typically resolving after discontinuation of therapy.

Other adverse reactions reported include chest pain, abdominal pain, syncope, chest discomfort, fever, trauma, and viral infections. Cardiovascular effects may involve palpitations and orthostatic hypotension. Digestive system reactions can include gastrointestinal cramps, dry mouth, constipation, and heartburn. Musculoskeletal complaints such as back pain, shoulder pain, knee pain, back strain, myalgia, and foot pain have also been reported.

Nervous and psychiatric effects may manifest as decreased libido, vertigo, depression, and somnolence. Respiratory issues include common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, allergic rhinitis, and pharyngeal discomfort. Skin reactions may involve flushing, pruritus, skin inflammation, diaphoresis, and cutaneous pseudolymphoma. Special senses may be affected, leading to blurred vision, tinnitus, and otalgia. Urogenital adverse reactions include urinary tract infections.

In post-marketing experience, hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma, in white patients receiving large cumulative doses.

Drug Interactions

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

Pharmacodynamic Interactions

• Diuretics: The initiation of lisinopril in patients who are on diuretics, particularly those recently started on diuretic therapy, may lead to excessive hypotension. To mitigate this risk, it is advisable to consider discontinuing the diuretic or increasing dietary salt intake prior to starting lisinopril.

• Non-Steroidal Anti-Inflammatory Agents (NSAIDs): Co-administration of NSAIDs, including selective COX-2 inhibitors, can lead to deterioration of renal function, potentially resulting in acute renal failure, especially in elderly patients, those who are volume-depleted, or individuals 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, such as angiotensin receptor blockers or aliskiren, is associated with an increased risk of hypotension, hyperkalemia, and alterations in renal function, including acute renal failure.

• Aliskiren: Lisinopril should not be co-administered with hydrochlorothiazide in patients with diabetes or renal impairment (GFR < 60 ml/min).

• Agents Increasing Serum Potassium: The concomitant use of lisinopril with potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium levels. Caution is advised, and frequent monitoring of serum potassium is recommended.

• Lithium: The use of lisinopril in conjunction with lithium has been associated with lithium toxicity. Therefore, serum lithium levels should be monitored closely when these medications are used together.

• mTOR Inhibitors: Co-administration of lisinopril with mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) may heighten the risk of angioedema.

• Neprilysin Inhibitors: The concurrent use of neprilysin inhibitors with lisinopril increases the risk of angioedema.

Pharmacokinetic Interactions

Hydrochlorothiazide also presents several interactions that may necessitate dosage adjustments or monitoring.

• Alcohol, Barbiturates, or Narcotics: These substances may enhance the risk of orthostatic hypotension when used with hydrochlorothiazide.

• Antidiabetic Drugs: Dosage adjustments may be required for antidiabetic medications when administered alongside hydrochlorothiazide.

• Other Antihypertensive Drugs: The use of hydrochlorothiazide with other antihypertensive agents may result in additive effects or potentiation.

• Cholestyramine and Colestipol Resins: These resins can impair the absorption of hydrochlorothiazide, with cholestyramine potentially reducing absorption by up to 85%.

• Corticosteroids and ACTH: The combination may exacerbate electrolyte depletion, particularly hypokalemia.

• Pressor Amines (e.g., Norepinephrine): There may be a decreased response to pressor amines, although this is not sufficient to contraindicate their use.

• Skeletal Muscle Relaxants (e.g., Tubocurarine): Increased responsiveness to muscle relaxants may occur when used with hydrochlorothiazide.

• Lithium: The use of hydrochlorothiazide with lithium is generally discouraged due to the risk of reduced renal clearance and increased potential for lithium toxicity.

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): The antihypertensive, diuretic, and natriuretic effects of hydrochlorothiazide may be diminished when used with NSAIDs. Close monitoring is warranted in such cases.

• Gold: Rare nitritoid reactions, including facial flushing, nausea, vomiting, and hypotension, have been reported with the use of injectable gold in conjunction with ACE inhibitors.

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 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 may 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

Clinical studies of lisinopril and hydrochlorothiazide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly patients and younger individuals.

In general, dose selection for geriatric patients should be approached with caution. It is advisable to start at the low end of the dosing range, taking into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies. This drug is substantially excreted by the kidneys, and the risk of toxic reactions may be heightened in patients with impaired renal function.

Given that elderly patients are more prone to renal function decline, careful consideration should be given to dose selection. Furthermore, the evaluation of hypertensive elderly patients should always include an assessment of renal function to ensure safe and effective treatment.

Pregnancy

Drugs that act directly on the renin-angiotensin system, including lisinopril and hydrochlorothiazide, carry a significant risk of fetal toxicity. The use of these medications during the second and third trimesters of pregnancy is classified as Pregnancy Category D, indicating evidence of risk to the fetus. Specifically, exposure can lead to reduced fetal renal function, increased morbidity, and mortality. Oligohydramnios, a potential consequence of such exposure, may result in fetal lung hypoplasia and skeletal deformations.

When pregnancy is detected, it is imperative to discontinue lisinopril and hydrochlorothiazide as soon as possible. In cases where there is no appropriate alternative therapy, healthcare providers should inform the patient of the potential risks to the fetus. Serial ultrasound examinations are recommended to monitor the intra-amniotic environment; if oligohydramnios is identified, these medications should be discontinued unless deemed lifesaving for the mother.

Neonatal adverse effects associated with in utero exposure may include skull hypoplasia, anuria, hypotension, renal failure, and even death. Infants with a history of exposure to these medications should be closely monitored for hypotension, oliguria, and hyperkalemia. While no teratogenic effects have been observed in studies involving pregnant rats, mice, and rabbits, the potential for serious fetal injury during the second and third trimesters necessitates careful management of maternal hypertension to optimize outcomes for both mother and fetus.

Healthcare professionals should remain vigilant, as oligohydramnios may not manifest until after the fetus has sustained irreversible injury. Fetal testing may be warranted based on gestational age to ensure appropriate monitoring and intervention.

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 the combination, 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 the drug to the mother when making decisions regarding the continuation of nursing or the discontinuation of lisinopril and hydrochlorothiazide.

Renal Impairment

Patients with severe renal dysfunction should not use thiazide-containing combination products, as these may precipitate azotemia and lead to cumulative effects. In individuals with renal disease, periodic monitoring of white blood cell counts is advisable, particularly for those with collagen vascular disease.

Excessive hypotension has been noted in patients with severe congestive heart failure, regardless of renal function status, and may result in oliguria, progressive azotemia, and, in rare cases, acute renal failure or death.

Patients receiving ACE inhibitors, including lisinopril, may experience a range of adverse reactions, some of which can be serious, especially in those with renal impairment. Additionally, individuals with a history of angioedema not related to ACE-inhibitor therapy may face an increased risk of angioedema while on an ACE inhibitor. Anaphylactoid reactions have also been documented in patients undergoing dialysis with high-flux membranes who are treated concurrently with an ACE inhibitor; in such cases, dialysis should be halted immediately.

Close monitoring of hypotension and renal function is essential for patients on dialysis.

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 protocols are not well established. Management is primarily symptomatic and supportive. It is recommended that therapy with both medications be discontinued immediately, and the patient should be monitored closely for any adverse effects.

Recommended Actions

In the event of suspected overdosage, healthcare professionals should consider the following measures:

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

• Correction of dehydration, electrolyte imbalances, and hypotension should be performed using established medical procedures.

Potential Symptoms

The most likely manifestation of overdosage is hypotension. In animal studies, a single oral dose of 20 g/kg did not result in lethality in rats; however, one out of twenty mice did not survive this dosage. Therefore, vigilance is necessary in monitoring blood pressure and other vital signs.

Management Procedures

For hypotension resulting from overdosage, the usual treatment involves the intravenous infusion of normal saline solution to restore hemodynamic stability. Additionally, it is important to note that lisinopril can be effectively removed from the system through hemodialysis, which may be considered in severe cases of overdosage.

Overall, the management of overdosage with lisinopril and hydrochlorothiazide should be tailored to the individual patient's needs, with a focus on supportive care and monitoring.

Nonclinical Toxicology

No teratogenic effects of lisinopril were observed in studies involving pregnant rats, mice, and rabbits. The doses administered were significantly higher than the maximum recommended human dose, with up to 625 times the dose in mice, 188 times in rats, and 0.6 times in rabbits. In teratogenicity studies conducted with mice and rats, lisinopril was given in combination with hydrochlorothiazide at doses up to 90 mg/kg/day (56 times the maximum recommended human dose) and 10 mg/kg/day (2.5 times the maximum recommended human dose), respectively. Maternal or fetotoxic effects were not noted in mice receiving the combination. However, in rats, decreased maternal weight gain and reduced fetal weight were observed at the lowest tested dose of 3/10 mg/kg/day, which was associated with a delay in fetal ossification. These adverse effects were not present in saline-supplemented animals receiving the same combination of doses. It is recommended to discontinue lisinopril and hydrochlorothiazide as soon as pregnancy is detected, as adverse outcomes are typically linked to the use of these medications during the second and third trimesters.

Potential non-teratogenic neonatal adverse effects associated with the use of these medications include skull hypoplasia, anuria, hypotension, renal failure, and death. Hydrochlorothiazide may also lead to fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions.

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. There were no increases in chromosomal aberrations observed in either an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow.

Long-term studies indicated 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). 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).

Studies in rats demonstrated that lisinopril poorly crosses the blood-brain barrier, and multiple doses do not lead to tissue accumulation. However, radioactivity was detected in the milk of lactating rats following administration of labeled lisinopril. Whole body autoradiography revealed radioactivity in the placenta of pregnant rats, but none was found in the fetuses. Hydrochlorothiazide, classified as a sulfonamide, may cause an idiosyncratic reaction leading to acute transient myopia and acute angle-closure glaucoma, with symptoms such as a sudden decrease in visual acuity or ocular pain typically occurring within hours to weeks after initiation of treatment.

Postmarketing Experience

Hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC). Data from a study conducted within the Sentinel System indicate that this increased risk is most pronounced in white patients who have received large cumulative doses of the medication. Specifically, the overall population exhibits an approximate risk of 1 additional case of SCC per 16,000 patients per year. For white patients who have taken a cumulative dose of 50,000 mg or more, the risk escalates to approximately 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 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 informed 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 made aware of the potential consequences of exposure to lisinopril and hydrochlorothiazide during pregnancy. It is essential 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 advised 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 National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature.

It is essential to protect the product from excessive light and humidity to maintain its integrity and efficacy. Proper storage conditions are crucial for ensuring the quality of the product throughout its shelf life.

Additional Clinical Information

Periodic monitoring of serum electrolytes is recommended to identify potential electrolyte imbalances in patients. Clinicians should assess renal function in hypertensive patients, as minor reversible increases in blood urea nitrogen and serum creatinine have been noted in those treated with lisinopril and hydrochlorothiazide. Additionally, small decreases in hemoglobin and hematocrit levels 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 or difficulty breathing, and to refrain from taking additional medication until consulting their physician. They should be advised to monitor for lightheadedness, particularly during the initial days of treatment, and to discontinue use if syncope occurs. Caution is advised against using potassium-containing salt substitutes without medical consultation. Patients should promptly report any signs of infection, which may indicate leukopenia or 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. Furthermore, those taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and to undergo regular skin cancer screenings. Notably, hydrochlorothiazide has been linked to an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma, especially in white patients receiving high cumulative doses.

FDA Insert (PDF)

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

View full prescribing information (PDF)