Lisinopril and Hydrochlorothiazide

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 441.52. Lisinopril appears as a white to off-white, crystalline powder and 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 297.73. 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 available for oral use in three tablet combinations: 10 mg/12.5 mg, 20 mg/12.5 mg, and 20 mg/25 mg. The inactive ingredients for the 10 mg/12.5 mg tablets include dibasic calcium phosphate dihydrate, magnesium stearate, mannitol, and pregelatinized starch. The 20 mg/12.5 mg tablets contain dibasic calcium phosphate dihydrate, magnesium stearate, mannitol, pregelatinized starch, and yellow ferric oxide. The 20 mg/25 mg tablets consist of dibasic calcium phosphate dihydrate, magnesium stearate, mannitol, pregelatinized starch, and red ferric oxide.

Uses and Indications

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

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

Clinical studies have demonstrated that numerous antihypertensive medications can significantly reduce cardiovascular morbidity and mortality, with blood pressure reduction being a key factor in these outcomes. The most substantial and consistent 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 associated with 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 various populations, with patients at higher baseline risk—such as those with diabetes or hyperlipidemia—experiencing greater absolute benefits.

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

Dosage and Administration

Lisinopril monotherapy is administered in 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 for lisinopril is between 10 mg and 80 mg, while hydrochlorothiazide should be dosed from 6.25 mg to 50 mg. In cases where blood pressure remains inadequately controlled with either monotherapy, a switch to lisinopril and hydrochlorothiazide tablets at doses of 10 mg/12.5 mg or 20 mg/12.5 mg may be considered.

Further increases in the dosage of either component should be based on the clinical response of the patient. It is important to note that the hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have passed since the last adjustment. Dosages exceeding 80 mg of lisinopril and 50 mg of hydrochlorothiazide are not recommended.

The combination therapy may be substituted for the titrated individual components without requiring dosage adjustments for patients with a creatinine clearance greater than 30 mL/min/1.73 m² (serum creatinine approximately less than or equal to 3 mg/dL or 265 μmol/L).

Contraindications

Lisinopril and hydrochlorothiazide tablets are contraindicated in patients with hypersensitivity to any component of the formulation. The use of this product is also contraindicated in individuals with a history of angioedema associated with prior treatment using an angiotensin-converting enzyme (ACE) inhibitor, as well as in those with hereditary or idiopathic angioedema.

Due to the presence of hydrochlorothiazide, this medication is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Additionally, the combination of lisinopril and hydrochlorothiazide is contraindicated with neprilysin inhibitors, such as sacubitril; administration should not occur within 36 hours of switching to or from sacubitril/valsartan. Furthermore, coadministration of aliskiren with lisinopril and hydrochlorothiazide is contraindicated in patients with diabetes.

Warnings and Precautions

Patients receiving ACE inhibitors, including lisinopril, may experience serious adverse reactions, including anaphylactoid and possibly related reactions. It is crucial for healthcare professionals to be vigilant for signs of these reactions, as they can occur at any time during treatment.

Angioedema Risks Head and neck angioedema, although rare, has been reported in patients treated with ACE inhibitors. This condition may occur at any point during therapy and is observed at higher rates in Black patients. If angioedema occurs, lisinopril should be discontinued immediately, and appropriate therapy should be initiated. Additionally, intestinal angioedema has been documented in patients on ACE inhibitors, typically diagnosed through abdominal CT scan or ultrasound, with symptoms resolving upon cessation of the medication.

Desensitization Considerations Life-threatening anaphylactoid reactions have been reported in patients receiving ACE inhibitors during desensitization treatment. Therefore, caution is advised when administering lisinopril in such scenarios.

Hypotension and Monitoring Excessive hypotension may occur, particularly in patients who are salt or volume-depleted. Close medical supervision is essential for patients with severe congestive heart failure to mitigate this risk.

Hematological Monitoring Rare cases of neutropenia and agranulocytosis have been reported, necessitating periodic monitoring of white blood cell counts, especially in patients with renal disease.

Hepatic Considerations Lisinopril has been rarely associated with hepatic failure, which may present as cholestatic jaundice or hepatitis that can progress to fulminant hepatic necrosis.

General Precautions Caution is advised when prescribing lisinopril to patients with aortic stenosis or hypertrophic cardiomyopathy due to potential obstruction in the outflow tract of the left ventricle. Changes in renal function may occur, particularly in patients with renal artery stenosis, necessitating regular monitoring of renal function. Hyperkalemia has been observed in approximately 1.4% of patients; therefore, it is important to use lisinopril cautiously in conjunction with potassium-sparing diuretics and to monitor serum potassium levels. A persistent nonproductive cough may develop during treatment but typically resolves after discontinuation of the medication. Furthermore, lisinopril may inhibit angiotensin II formation during major surgery or anesthesia, which could lead to hypotension.

Laboratory Monitoring Healthcare professionals should ensure periodic determination of serum electrolytes to detect potential imbalances at appropriate intervals. Monitoring of renal function is particularly important during the initial weeks of therapy in patients with renal artery stenosis. Serum and urine electrolyte determinations are also critical in patients experiencing excessive vomiting or receiving parenteral fluids.

Emergency Response In the event of angioedema, especially with involvement of the tongue, glottis, or larynx, immediate medical intervention is required. Subcutaneous epinephrine and/or measures to ensure a patent airway should be promptly administered.

Pregnancy Considerations Lisinopril and hydrochlorothiazide tablets should be discontinued as soon as pregnancy is detected, and the patient should be advised to contact their healthcare provider.

Side Effects

Adverse reactions associated with the use of PRINZIDE have been categorized based on their frequency and seriousness.

Common adverse reactions observed in clinical trials include dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), and orthostatic effects (3.2%). Other common reactions reported include diarrhea (2.5%), nausea (2.2%), upper respiratory infection (2.2%), muscle cramps (2.0%), asthenia (1.8%), paresthesia (1.5%), hypotension (1.4%), vomiting (1.4%), dyspepsia (1.3%), rash (1.2%), and impotence (1.2%).

In addition to these common reactions, a range of additional adverse reactions has been reported. These include chest pain, abdominal pain, syncope, chest discomfort, fever, and viral infections under the category of body as a whole. Cardiovascular effects may include palpitations and orthostatic hypotension. Digestive system reactions encompass gastrointestinal cramps, dry mouth, constipation, and heartburn. Musculoskeletal complaints include back pain, shoulder pain, knee pain, back strain, myalgia, and foot pain. Nervous and psychiatric effects may manifest as decreased libido, vertigo, depression, and somnolence. Respiratory issues reported 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, and diaphoresis. Special senses may be affected, leading to blurred vision, tinnitus, and otalgia. Urogenital adverse reactions include urinary tract infections.

Warnings associated with PRINZIDE include the risk of angioedema, which has been reported more frequently in Black patients compared to non-Black patients. Angioedema involving laryngeal edema can be fatal; therefore, if symptoms such as swelling of the face, extremities, lips, tongue, glottis, or larynx occur, treatment should be discontinued immediately, and appropriate therapy should be initiated. Rare cases of intestinal angioedema have also been reported with angiotensin-converting enzyme inhibitors, including lisinopril.

Hypotension-related adverse effects were noted in clinical trials, with hypotension occurring in 1.4% of patients, orthostatic hypotension in 0.5%, and other orthostatic effects in 3.2%. Syncope was reported in 0.8% of participants. Additionally, a persistent nonproductive cough has been documented with all ACE inhibitors, which resolves upon discontinuation of therapy.

Specific adverse reactions related to hydrochlorothiazide include weakness, anorexia, gastric irritation, cramping, jaundice (intrahepatic cholestatic jaundice), pancreatitis, sialadenitis, and constipation. Hematologic reactions may involve leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, and hemolytic anemia. Musculoskeletal reactions can include muscle spasms, while nervous system and psychiatric effects may present as restlessness. Renal adverse reactions include renal failure, renal dysfunction, and interstitial nephritis. Skin reactions associated with hydrochlorothiazide may include erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis (including toxic epidermal necrolysis), and alopecia. Hypersensitivity reactions can manifest as purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress (including pneumonitis and pulmonary edema), and anaphylactic reactions.

Furthermore, hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC), in white patients receiving large cumulative doses.

Drug Interactions

Patients receiving lisinopril may experience 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 excessive hypotension. It is advisable to consider discontinuing the diuretic or increasing salt intake prior to starting lisinopril.

• NSAIDs: Co-administration of NSAIDs with lisinopril can result in renal function deterioration and may reduce the antihypertensive effect of lisinopril. Renal function should be monitored periodically in these patients.

• Dual RAS Blockade: The concurrent use of lisinopril with other agents that block the renin-angiotensin system (RAS) increases the risk of hypotension, hyperkalemia, and changes in renal function. Close monitoring is recommended.

• Aliskiren: The use of aliskiren in combination with lisinopril is contraindicated in diabetic patients and in those with renal impairment (GFR <60 ml/min).

• Potassium-Sparing Diuretics and Supplements: Lisinopril may elevate serum potassium levels when used with potassium-sparing diuretics or potassium supplements. Serum potassium levels should be monitored.

• Lithium: Concurrent use of lisinopril and lithium may lead to lithium toxicity; therefore, frequent monitoring of serum lithium levels is essential.

• Neprilysin Inhibitors: Patients taking neprilysin inhibitors may have an increased risk of angioedema when combined with lisinopril.

• ACE Inhibitors and mTOR Inhibitors: The coadministration of ACE inhibitors, including lisinopril, with mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) may heighten the risk of angioedema.

• Injectable Gold: Nitritoid reactions, characterized by flushing, nausea, vomiting, and hypotension, may occur when lisinopril is administered with injectable gold.

Pharmacokinetic Interactions:

• Hydrochlorothiazide and Other Medications: Alcohol, barbiturates, or narcotics may enhance the risk of orthostatic hypotension when used with hydrochlorothiazide.

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

• Cholestyramine and Colestipol Resins: The absorption of hydrochlorothiazide can be significantly impaired by cholestyramine and colestipol resins, potentially reducing absorption by up to 85% and 43%, respectively.

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

• Lithium and Diuretics: The combination of lithium with diuretics is generally not recommended due to an increased risk of toxicity; renal clearance should be monitored closely.

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs may diminish the diuretic effects of both lisinopril and hydrochlorothiazide. Patient response should be monitored closely in these cases.

Packaging & NDC

The table below lists all NDC Code configurations of Lisinopril and Hydrochlorothiazide (lisinopril and hydrochlorothiazide tablets), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Neonates with a history of in utero exposure to lisinopril and hydrochlorothiazide tablets may experience complications such as oliguria or hypotension. In such cases, it is crucial to provide support for blood pressure and renal perfusion. Management may necessitate interventions such as exchange transfusions or dialysis to address hypotension and substitute for impaired renal function.

Lisinopril is known to cross the placenta, and there have been instances where peritoneal dialysis has successfully removed the drug from neonatal circulation, demonstrating some clinical benefit. Although theoretically, exchange transfusion could also facilitate the removal of lisinopril, there is currently no clinical experience to support this procedure in practice.

Geriatric Use

Elderly patients, defined as those aged 65 and older, were not adequately represented in clinical studies of lisinopril and hydrochlorothiazide tablets, making it difficult to ascertain whether they respond differently compared to younger patients. However, other clinical experiences have not indicated significant differences in responses between elderly and younger patients.

When prescribing this medication to geriatric patients, it is essential to exercise caution in dose selection. Typically, treatment should begin at the lower end of the dosing range due to the increased likelihood of diminished hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies.

Pharmacokinetic studies have demonstrated that the area under the plasma concentration time curve (AUC) for lisinopril increased by approximately 120% and for hydrochlorothiazide by about 80% in elderly hypertensive patients compared to their younger counterparts. This significant increase underscores the importance of careful monitoring and potential dose adjustments in this population.

Given that this drug is primarily excreted by the kidneys, the risk of adverse reactions may be heightened in patients with impaired renal function, which is more common among the elderly. Therefore, it is crucial to assess renal function as part of the evaluation of hypertensive elderly patients to ensure safe and effective treatment.

Pregnancy

Lisinopril-Hydrochlorothiazide is not indicated for use during pregnancy. Lisinopril is contraindicated in pregnancy due to the significant risk of fetal harm, which may result in injury or death of the developing fetus. Hydrochlorothiazide is also not recommended during pregnancy, as it may contribute to fetal harm.

There are no adequate and well-controlled studies in pregnant women regarding the use of Lisinopril or Hydrochlorothiazide. Additionally, animal reproduction studies have not been conducted with Lisinopril-Hydrochlorothiazide. Therefore, it is advised that Lisinopril-Hydrochlorothiazide be discontinued as soon as pregnancy is detected to mitigate potential risks to fetal outcomes.

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 levels in rat milk being 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 reactions in nursing infants from ACE inhibitors and hydrochlorothiazide, healthcare professionals should consider the importance of lisinopril and hydrochlorothiazide tablets to the mother when making a decision to either discontinue nursing or discontinue the medication.

Renal Impairment

Patients with renal impairment should be treated with caution, particularly when using thiazides, as these agents may precipitate azotemia and exhibit cumulative effects in individuals with reduced kidney function. In cases of severe renal disease, careful monitoring is essential.

The use of lisinopril in patients with renal impairment necessitates vigilance due to the potential for neutropenia and agranulocytosis. While data from clinical trials do not definitively establish a causal relationship, rare instances of these conditions have been reported, particularly in patients with concurrent collagen vascular diseases. Therefore, periodic monitoring of white blood cell counts is advisable in this population.

In patients with severe congestive heart failure, whether or not accompanied by renal insufficiency, there is a risk of excessive hypotension, which may lead to oliguria, progressive azotemia, and, in rare cases, acute renal failure or death. Initiation of therapy in these patients should occur under close medical supervision, with careful follow-up during the first two weeks and upon any dose adjustments of lisinopril or diuretics.

Excessive hypotension is less common in uncomplicated hypertensive patients but remains a concern in those who are salt/volume-depleted, such as individuals receiving aggressive diuretic therapy or those on dialysis.

Additionally, patients receiving a combination of an ACE inhibitor and mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) or a neprilysin inhibitor may face an increased risk of angioedema.

Hydrochlorothiazide should also be used cautiously in patients with impaired hepatic function or progressive liver disease, as even minor alterations in fluid and electrolyte balance could 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, and in some cases, 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 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 tablets, specific treatment protocols are not established; therefore, management is primarily symptomatic and supportive.

Recommended Actions

For suspected overdosage, the following measures are suggested:

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

• It is essential to correct any dehydration, electrolyte imbalances, and hypotension that may arise as a result of the overdosage.

Potential Symptoms

The most likely manifestation of lisinopril overdosage is hypotension. In such instances, the standard treatment involves the intravenous infusion of normal saline solution to restore blood pressure. Additionally, if digitalis has been administered concurrently, hypokalemia may exacerbate the risk of cardiac arrhythmias.

Management Procedures

Lisinopril can be effectively removed from the system through hemodialysis, which may be beneficial in cases of significant overdosage.

In animal studies, a single oral dose of 20 g/kg of lisinopril did not result in lethality in rats, although one out of twenty mice did not survive the same dosage. For hydrochlorothiazide, a single oral dose of 10 g/kg was also non-lethal in both mice and rats; however, it is important to monitor for signs of electrolyte depletion and dehydration due to excessive diuresis.

Healthcare professionals should remain vigilant for these symptoms and manage them accordingly to ensure patient safety and recovery.

Nonclinical Toxicology

No teratogenic effects were observed in the studies conducted. In terms of non-teratogenic effects, lisinopril did not adversely affect reproductive performance in male and female rats treated with doses up to 300 mg/kg/day, which is 33 times the maximum recommended human daily dose (MRHDD) when adjusted for body surface area. Similarly, hydrochlorothiazide did not demonstrate adverse effects on fertility in mice and rats of either sex when administered dietary doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to conception and throughout gestation. These doses correspond to 9 times and 0.7 times the MRHDD based on body surface area.

Lisinopril in combination with hydrochlorothiazide was evaluated for mutagenicity and found to be non-mutagenic in a microbial mutagen test using Salmonella typhimurium (Ames test) and Escherichia coli, both with and without metabolic activation. Additionally, it did not induce DNA single strand breaks in an in vitro alkaline elution assay using rat hepatocytes, nor did it result in increases in chromosomal aberrations in either an in vitro test with Chinese hamster ovary cells or an in vivo study involving mouse bone marrow. Long-term studies indicated no tumorigenic effects when lisinopril was administered orally for 105 weeks to male and female rats at doses up to 90 mg/kg/day or for 92 weeks to male and female mice at doses up to 135 mg/kg/day, which are 10 times and 7 times the MRHDD, respectively.

Hydrochlorothiazide was also assessed for carcinogenic potential in two-year feeding studies conducted by the National Toxicology Program (NTP). No evidence of carcinogenicity was found in female mice at doses up to approximately 600 mg/kg/day (53 times the MRHDD) or in male and female rats at doses up to approximately 100 mg/kg/day (18 times the MRHDD). However, the NTP reported equivocal evidence for hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in in vitro assays, including the Ames test for Salmonella typhimurium and the Chinese Hamster Ovary test for chromosomal aberrations, nor in in vivo assays involving mouse germinal cell chromosomes and Chinese hamster bone marrow chromosomes. Positive results were noted only in the in vitro CHO Sister Chromatid Exchange and Mouse Lymphoma Cell assays, as well as in the Aspergillus nidulans non-disjunction assay, under specific conditions.

Postmarketing Experience

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

Angioedema has been documented in patients receiving PRINZIDE, with a higher incidence observed in Black patients compared to non-Black patients. This condition, particularly when associated with laryngeal edema, may be life-threatening. In cases of angioedema affecting the face, extremities, lips, tongue, glottis, and/or larynx, discontinuation of PRINZIDE and immediate initiation of appropriate therapy is recommended. Additionally, rare instances of intestinal angioedema have been reported among patients treated with angiotensin-converting enzyme (ACE) inhibitors, including lisinopril. These patients often presented with abdominal pain, which may occur without prior facial angioedema, and were diagnosed through imaging or surgical procedures.

Hypotension-related adverse effects were noted in clinical trials, with an incidence of hypotension at 1.4%, orthostatic hypotension at 0.5%, and other orthostatic effects at 3.2%. Syncope was reported in 0.8% of patients.

Rare cases of neutropenia, thrombocytopenia, and bone marrow depression have also been reported. Hemolytic anemia has been observed, although a causal relationship with lisinopril cannot be definitively established.

Patients with a history of angioedema unrelated to ACE-inhibitor therapy may have an increased risk of developing angioedema while on ACE inhibitors. Furthermore, coadministration of ACE inhibitors with mTOR inhibitors (such as temsirolimus, sirolimus, or everolimus) or neprilysin inhibitors may elevate the risk of angioedema.

For reporting side effects, patients and healthcare professionals are encouraged to contact Solco Healthcare US, LLC at 1-866-257-2597 or the FDA at 1-800-FDA-1088.

Patient Counseling

Healthcare providers should advise patients to discontinue lisinopril and hydrochlorothiazide tablets as soon as pregnancy is detected. It is important for patients to report any side effects they experience to Solco Healthcare US, LLC at 1-866-257-2597 or the FDA at 1-800-FDA-1088.

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

Caution patients to be aware of lightheadedness, particularly during the initial days of therapy. If they experience actual syncope, they should discontinue the medication and consult their physician before resuming treatment. Additionally, 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 aware that other factors, such as vomiting or diarrhea, may contribute to this risk and should consult their physician if these occur.

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

For female patients of childbearing age, it is essential to discuss the potential consequences of exposure to lisinopril and hydrochlorothiazide tablets during pregnancy. Healthcare providers should engage in discussions about treatment options for women planning to become pregnant and encourage them to report any pregnancies to their physicians as soon as possible.

Finally, 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 a well-closed container to ensure integrity, particularly if the package has been subdivided. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C and 30°C (59°F to 86°F) in accordance with USP Controlled Room Temperature guidelines. Additionally, it is essential to protect the product from excessive light and humidity to maintain its quality and efficacy.

Additional Clinical Information

Periodic determination of serum electrolytes is recommended to monitor for potential electrolyte imbalances in patients, particularly during instances of excessive vomiting or when receiving parenteral fluids. Clinicians should be aware that thiazide diuretic therapy may lead to increased cholesterol and triglyceride levels, and thiazides should be discontinued prior to conducting parathyroid function tests.

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 take additional medication until consulting their physician. Lightheadedness, especially in the initial days of therapy, should be reported, and if syncope occurs, patients should discontinue the drug and seek medical advice. Patients are also advised to be cautious of excessive perspiration and dehydration, which can lead to significant drops in blood pressure. Additionally, they should avoid potassium-containing salt substitutes without prior consultation and report any signs of infection that may indicate neutropenia. Female patients of childbearing age should be informed about the risks associated with the medication during pregnancy and should report any pregnancies to their healthcare provider. Lastly, those taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and to undergo regular skin cancer screenings.

FDA Insert (PDF)

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

View full prescribing information (PDF)