Lisinopril/Hydrochlorothiazide

Description

Lisinopril and Hydrochlorothiazide Tablets combine an angiotensin converting enzyme inhibitor, lisinopril, and a diuretic, hydrochlorothiazide. Lisinopril is a synthetic peptide derivative, chemically described as (S)-1-N^2-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline dihydrate, with a molecular formula of C21H31N3O5 • 2H2O and a molecular weight of 441.52. 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 a molecular formula of C7H8ClN3O4S2 and a molecular weight of 297.73. This compound is a white or practically white crystalline powder, slightly soluble in water, and freely soluble in sodium hydroxide solution.

Lisinopril and Hydrochlorothiazide Tablets are formulated for oral administration in three combinations: 10 mg lisinopril and 12.5 mg hydrochlorothiazide (10 mg/12.5 mg), 20 mg lisinopril and 12.5 mg hydrochlorothiazide (20 mg/12.5 mg), and 20 mg lisinopril and 25 mg hydrochlorothiazide (20 mg/25 mg). Inactive ingredients include dibasic calcium phosphate, magnesium stearate, mannitol, pregelatinized starch (maize starch), and starch. The 10 mg/12.5 mg and 20 mg/25 mg formulations also contain ferric oxide red and ferric oxide yellow, while the 20 mg/12.5 mg formulation contains ferric oxide yellow.

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.

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

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

It is also acknowledged that some antihypertensive medications may exhibit diminished blood pressure-lowering effects when used as monotherapy in black patients. Additionally, many of these medications 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 between 6.25 mg and 50 mg. It is important to note that the hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed to allow for adequate assessment of the patient's response.

Doses exceeding 80 mg of lisinopril or 50 mg of hydrochlorothiazide are not recommended. For patients whose blood pressure remains inadequately controlled with either monotherapy, a transition to Lisinopril and Hydrochlorothiazide Tablets at doses of 10 mg/12.5 mg or 20 mg/12.5 mg may be considered. Subsequent adjustments to the dosage of either or both components should be based on the clinical response observed in the patient.

Contraindications

Lisinopril and Hydrochlorothiazide Tablets are contraindicated in the following situations:

Patients with hypersensitivity to any component of this product should not use Lisinopril and Hydrochlorothiazide Tablets. Additionally, the product is contraindicated in individuals with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor, as well as those with hereditary or idiopathic angioedema.

The use of this medication is also contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs due to the hydrochlorothiazide component. Furthermore, Lisinopril and Hydrochlorothiazide Tablets should not be administered in combination with a neprilysin inhibitor, such as sacubitril, and should not be given within 36 hours of switching to or from sacubitril/valsartan.

Lastly, coadministration of aliskiren with Lisinopril and Hydrochlorothiazide Tablets 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 reactions, including those potentially related to treatment, have been documented. Healthcare professionals should be vigilant for signs of these reactions, particularly in patients undergoing desensitization therapy or those exposed to high-flux dialysis membranes, as life-threatening events have been reported in these contexts.

Angioedema, both in the head and neck region and intestines, has been observed in patients treated with ACE inhibitors. Head and neck angioedema can occur at any time during treatment and necessitates prompt discontinuation of the medication and appropriate therapeutic intervention. Intestinal angioedema may present with abdominal pain, with symptoms typically resolving upon cessation of the ACE inhibitor.

Excessive hypotension may occur in patients who are salt or volume-depleted, particularly those with severe congestive heart failure, necessitating close medical supervision. Additionally, rare cases of neutropenia and agranulocytosis have been reported, particularly in patients with collagen vascular disease and renal disease; therefore, periodic monitoring of white blood cell counts is advisable in these populations.

Hepatic failure has been associated with ACE inhibitors, potentially leading to fulminant hepatic necrosis. Discontinuation of the medication is warranted if jaundice or significant elevations in hepatic enzymes are observed. Furthermore, the use of drugs that affect the renin-angiotensin system during the second and third trimesters of pregnancy poses a risk of fetal injury or death.

In terms of general precautions, Lisinopril should be administered with caution to patients with aortic stenosis or hypertrophic cardiomyopathy due to the potential for obstruction in the left ventricular outflow tract. Changes in renal function may occur in susceptible individuals; thus, renal function should be monitored during the initial weeks of therapy. The risk of hyperkalemia is heightened in patients with renal insufficiency or those taking potassium-sparing diuretics, necessitating regular monitoring of serum potassium levels. A persistent nonproductive cough has been reported with ACE inhibitors, which typically resolves after discontinuation of the drug.

During major surgical procedures or anesthesia, Lisinopril may inhibit angiotensin II formation, potentially leading to hypotension. Therefore, careful monitoring is essential in these situations.

Laboratory tests should include periodic determination of serum electrolytes to identify any electrolyte imbalances, as well as evaluations of renal function, which are critical in the management of hypertensive patients.

In cases of angioedema involving the tongue, glottis, or larynx, which may lead to airway obstruction, immediate medical intervention is required. Administration of subcutaneous epinephrine solution (1:1000, 0.3 mL to 0.5 mL) and measures to ensure airway patency should be promptly initiated.

Patients are advised to discontinue Lisinopril and Hydrochlorothiazide Tablets immediately upon detection of pregnancy and to consult their healthcare provider without delay.

Side Effects

Patients receiving Lisinopril and Hydrochlorothiazide Tablets may experience a range of adverse reactions. Common adverse reactions observed in clinical trials include dizziness (7.5%, with 0.8% leading to discontinuation), headache (5.2%, 0.3% discontinuation), and cough (3.9%, 0.6% discontinuation). Other frequently reported reactions include fatigue (3.7%, 0.4% discontinuation), orthostatic effects (3.2%, 0.1% discontinuation), diarrhea (2.5%, 0.2% discontinuation), and nausea (2.2%, 0.1% discontinuation). Upper respiratory infections and muscle cramps were reported in 2.2% and 2% of patients, respectively, with discontinuation rates of 0%. Additional common reactions include asthenia (1.8%, 0.2% discontinuation), paresthesia (1.5%, 0.1% discontinuation), hypotension (1.4%, 0.3% discontinuation), vomiting (1.4%, 0.1% discontinuation), dyspepsia (1.3%, 0% discontinuation), rash (1.2%, 0.1% discontinuation), and impotence (1.2%, 0.3% discontinuation).

Clinical adverse experiences with an incidence of 0.3% to 1% include a variety of symptoms across different systems. Patients may report chest pain, abdominal pain, syncope, and fever as part of general body reactions. Cardiovascular effects may include palpitations and orthostatic hypotension. Digestive issues such as gastrointestinal cramps, dry mouth, constipation, and heartburn have also been noted. Musculoskeletal complaints include back pain, shoulder pain, and myalgia. Nervous and psychiatric effects may manifest as decreased libido, vertigo, and depression. Respiratory symptoms can include common cold, nasal congestion, and dyspnea. Skin reactions such as flushing and pruritus, as well as sensory disturbances like blurred vision and tinnitus, have been reported. Urogenital issues, including urinary tract infections, are also possible.

Serious adverse reactions include angioedema, which has been reported in patients taking Lisinopril and Hydrochlorothiazide Tablets, with a higher incidence in Black patients compared to non-Black patients. Angioedema associated with laryngeal edema can be fatal; therefore, if this occurs, treatment should be discontinued immediately. Hypotension was noted in 1.4% of patients, with orthostatic hypotension occurring in 0.5% and syncope in 0.8%. A persistent nonproductive cough has been associated with all ACE inhibitors, resolving after discontinuation of therapy.

It is important to note that drugs affecting the renin-angiotensin system, such as Lisinopril and Hydrochlorothiazide, can cause fetal toxicity, leading to injury or death to the developing fetus. Therefore, these medications should be discontinued as soon as pregnancy is detected.

Drug Interactions

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

Pharmacodynamic Interactions:

• Diuretics: Patients on diuretics may experience an excessive reduction in blood pressure upon initiation of lisinopril therapy. Close monitoring of blood pressure is advised.

• NSAIDs: Co-administration of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, can lead to deterioration of renal function, particularly in elderly, volume-depleted patients, or those with pre-existing renal impairment. The antihypertensive effect of lisinopril may also be diminished by NSAIDs. Monitoring of renal function and blood pressure is recommended.

• Renin-Angiotensin System (RAS) Inhibitors: The use of dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or direct renin inhibitors (e.g., aliskiren) is associated with an increased risk of hypotension, syncope, hyperkalemia, and renal function changes. The combined use of RAS inhibitors should be avoided, and patients should be monitored for blood pressure, renal function, and electrolytes.

• Potassium-Sparing Agents: Lisinopril may attenuate potassium loss caused by thiazide-type diuretics. However, concomitant use with potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium levels.

• Lithium: The risk of lithium toxicity is increased when lithium is administered with ACE inhibitors. Serum lithium levels should be monitored frequently in patients receiving both medications.

• Angioedema Risk: Patients taking ACE inhibitors in conjunction with mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) or neprilysin inhibitors may be at an increased risk for angioedema.

• Gold Injections: Nitritoid reactions have been reported in patients receiving injectable gold alongside ACE inhibitors.

Pharmacokinetic Interactions:

• Propranolol, Digoxin, Hydrochlorothiazide: No significant pharmacokinetic interactions have been observed when lisinopril is used with propranolol, digoxin, or hydrochlorothiazide.

In the case of hydrochlorothiazide, several interactions warrant attention:

Pharmacodynamic Interactions:

• Alcohol and CNS Depressants: The use of alcohol, barbiturates, or narcotics may potentiate orthostatic hypotension. Patients should be advised to use caution when combining these agents.

• Antidiabetic Agents: Dosage adjustments may be necessary for antidiabetic drugs (both oral agents and insulin) when used concurrently with hydrochlorothiazide.

• Other Antihypertensives: The concomitant use of other antihypertensive medications may result in an additive effect or potentiation of blood pressure-lowering effects.

• Electrolyte Depletion: Corticosteroids and ACTH may exacerbate electrolyte depletion, particularly hypokalemia, necessitating monitoring of electrolyte levels.

• Lithium: The use of lithium with diuretics is generally contraindicated due to reduced renal clearance and an increased risk of lithium toxicity.

• NSAIDs: Non-steroidal anti-inflammatory drugs may diminish the diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide.

Pharmacokinetic Interactions:

• Cholestyramine and Colestipol: The absorption of hydrochlorothiazide is impaired in the presence of cholestyramine and colestipol resins, which may necessitate timing adjustments for administration.

• Pressor Amines: While pressor amines (e.g., norepinephrine) may exhibit a decreased response, they can still be utilized in conjunction with hydrochlorothiazide.

• Skeletal Muscle Relaxants: The responsiveness to skeletal muscle relaxants (e.g., tubocurarine) may be increased when used with hydrochlorothiazide.

Overall, careful monitoring and potential dosage adjustments are essential when managing patients on these medications to mitigate the risk of adverse interactions.

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

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, which is known to cross the placenta, has been effectively removed from neonatal circulation through peritoneal dialysis, demonstrating some clinical benefit. Although theoretically, exchange transfusion could also facilitate the removal of Lisinopril, there is currently no clinical experience to support this procedure.

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, available clinical experience has not indicated any significant differences in responses between elderly and younger patients.

In general, dose selection for geriatric patients should be approached with caution. It is advisable to initiate treatment at the lower end of the dosing range, taking into account the increased likelihood of diminished hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies.

Pharmacokinetic studies have demonstrated that the area under the plasma concentration time curve (AUC) for lisinopril increased by approximately 120% and for hydrochlorothiazide by approximately 80% in elderly hypertensive patients compared to their younger counterparts. This suggests that elderly patients may experience higher systemic exposure to these medications.

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 in the elderly population. Therefore, careful consideration should be given to dose selection in this demographic.

It is essential to evaluate renal function as part of the assessment for hypertensive elderly patients to ensure safe and effective treatment.

Pregnancy

Lisinopril, in combination with hydrochlorothiazide, has not demonstrated mutagenic potential in microbial mutagen tests. Long-term studies in animals have shown no evidence of tumorigenic effects; specifically, oral administration of lisinopril for 105 weeks in male and female rats and for 92 weeks in male and female mice did not result in tumor formation. Additionally, reproductive performance was unaffected in male and female rats treated with lisinopril at doses up to 300 mg/kg/day.

Hydrochlorothiazide has also been shown to have no adverse effects on fertility in both male and female mice and rats when administered prior to conception and throughout gestation.

While these findings suggest a lack of reproductive toxicity in animal studies, the safety of lisinopril and hydrochlorothiazide during pregnancy has not been established in human studies. Therefore, healthcare professionals should exercise caution when prescribing this combination to pregnant patients or women of childbearing potential. It is recommended that the potential benefits be weighed against any potential risks to the fetus.

Lactation

It is not known whether lisinopril is secreted in human milk. However, studies in lactating rats have shown that the milk contains radioactivity following the administration of 14C lisinopril, with another study indicating that lisinopril was present in rat milk at levels comparable to plasma levels in the dams. Thiazides, which are components of Lisinopril and Hydrochlorothiazide Tablets, are known to appear in human milk.

Due to the potential for serious reactions in nursing infants from ACE inhibitors and hydrochlorothiazide, healthcare professionals should consider the risks and benefits when advising lactating mothers. A decision should be made whether to discontinue nursing or to discontinue Lisinopril and Hydrochlorothiazide Tablets, taking into account the importance of the medication to the mother.

Renal Impairment

Patients with renal impairment should be treated with caution, particularly when using thiazides, as they may precipitate azotemia and lead to cumulative effects due to reduced kidney function. In cases of severe renal disease, thiazide use is not recommended.

Periodic monitoring of white blood cell counts is advisable for patients with collagen vascular disease and renal disease. Additionally, patients receiving ACE inhibitors, including Lisinopril, may experience serious adverse reactions, especially those with renal impairment.

Excessive hypotension has been observed in patients with severe congestive heart failure, with or without renal insufficiency, and may be associated with oliguria, progressive azotemia, and, in rare cases, acute renal failure or death. Caution is warranted when administering Lisinopril to patients with renal impairment, as it may further deteriorate renal function.

Close monitoring of renal function and blood pressure is essential for patients with renal impairment during treatment.

Hepatic Impairment

Patients with hepatic impairment should be closely monitored when receiving treatment with ACE inhibitors and thiazides. Rarely, ACE inhibitors 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 mechanism underlying this syndrome remains unclear. Therefore, it is imperative that patients receiving ACE inhibitors who develop jaundice or significant elevations in hepatic enzymes discontinue the medication immediately and receive appropriate medical follow-up.

Thiazides 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 information is limited. Management is primarily symptomatic and supportive. It is recommended that therapy with the tablets be discontinued, and the patient should be closely monitored for any adverse effects.

Recommended Actions

In the event of an overdose, healthcare professionals should consider the following measures:

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

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

Potential Symptoms

The most likely manifestation of an overdose is hypotension. In such cases, intravenous infusion of normal saline solution is the usual treatment. Additionally, the most common signs and symptoms associated with overdosage include those resulting from electrolyte depletion, such as hypokalemia, hypochloremia, and hyponatremia, as well as dehydration due to excessive diuresis. If digitalis has been administered concurrently, hypokalemia may exacerbate the risk of cardiac arrhythmias.

Toxicity Data

Toxicity studies indicate that a single oral dose of 20 g/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 g/kg was not lethal in either mice or rats.

Dialysis Consideration

Lisinopril can be effectively removed from the body through hemodialysis, which may be considered in severe cases of overdose.

In summary, the management of overdosage with Lisinopril and Hydrochlorothiazide Tablets should focus on supportive care, monitoring, and addressing any complications that arise.

Nonclinical Toxicology

No teratogenic effects were observed in the studies conducted. In non-teratogenic assessments, lisinopril administered to male and female rats at doses up to 300 mg/kg/day did not adversely affect reproductive performance, representing 33 times the maximum recommended human daily dose (MRHDD) when adjusted for body surface area. Hydrochlorothiazide also demonstrated no adverse effects on fertility in both male and female mice and rats exposed to dietary doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to conception and throughout gestation, corresponding to 9 times and 0.7 times the MRHDD based on body surface area.

In terms of mutagenicity, lisinopril in combination with hydrochlorothiazide was not found to be mutagenic in microbial mutagen tests using Salmonella typhimurium (Ames test) or Escherichia coli, with or without metabolic activation, nor in a forward mutation assay using Chinese hamster lung cells. Additionally, this combination did not induce DNA single strand breaks in an in vitro alkaline elution assay using rat hepatocytes, nor did it result in increased chromosomal aberrations in either an in vitro test in Chinese hamster ovary cells or an in vivo study in mouse bone marrow.

Long-term studies indicated no evidence of tumorigenicity for lisinopril when 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, when adjusted for body surface area. Lisinopril was consistently negative in mutagenicity assessments, including the Ames test and forward mutation assays, and did not produce single strand DNA breaks or chromosomal aberrations in the aforementioned tests.

Hydrochlorothiazide was evaluated in two-year feeding studies conducted by the National Toxicology Program (NTP), which revealed no carcinogenic potential 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). Furthermore, hydrochlorothiazide was not genotoxic in in vitro assays, including the Ames test and chromosomal aberration tests in Chinese hamster ovary cells, nor in in vivo assays involving mouse germinal cell chromosomes and Chinese hamster bone marrow chromosomes. Positive results were noted only in specific in vitro assays, including the CHO Sister Chromatid Exchange and Mouse Lymphoma Cell assays, under certain concentrations, as well as in the Aspergillus nidulans non-disjunction assay at unspecified concentrations.

Postmarketing Experience

Angioedema has been reported in patients receiving Lisinopril and Hydrochlorothiazide Tablets, with a higher incidence observed in Black patients compared to non-Black patients. Angioedema associated with laryngeal edema may be fatal; therefore, if angioedema of the face, extremities, lips, tongue, glottis, and/or larynx occurs, treatment with Lisinopril and Hydrochlorothiazide Tablets should be discontinued, and appropriate therapy should be instituted immediately.

In rare instances, intestinal angioedema has been reported with angiotensin-converting enzyme inhibitors, including lisinopril. Hypotension-related adverse effects were noted in clinical trials, with hypotension occurring in 1.4 percent of patients, orthostatic hypotension in 0.5 percent, and other orthostatic effects in 3.2 percent. Additionally, syncope was reported in 0.8 percent of patients.

Clinical adverse experiences occurring in more than one percent of patients treated with lisinopril plus hydrochlorothiazide in controlled clinical trials included dizziness (7.5 percent), headache (5.2 percent), cough (3.9 percent), fatigue (3.7 percent), and orthostatic effects (3.2 percent). Discontinuation of therapy due to adverse effects was necessary in 4.4 percent of patients, primarily due to dizziness, cough, fatigue, and muscle cramps.

Rare cases of neutropenia and bone marrow depression have been reported, and periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease is advisable. Additionally, ACE inhibitors have been rarely associated with a syndrome that begins with cholestatic jaundice or hepatitis and may progress to fulminant hepatic necrosis, and in some cases, death; the mechanism of this syndrome remains unclear.

Fetal toxicity has been observed with the use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy, leading to reduced fetal renal function and increased fetal and neonatal morbidity and mortality. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects may include skull hypoplasia, anuria, hypotension, renal failure, and death.

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 neutropenia.

Female patients of childbearing age should be made aware of the potential consequences of exposure to Lisinopril and Hydrochlorothiazide Tablets 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 20º to 25ºC (68º to 77ºF), 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. Proper storage conditions are crucial for ensuring the quality of the product throughout its shelf life.

Additional Clinical Information

Periodic determination of serum electrolytes is recommended for patients to detect potential electrolyte imbalances, and the evaluation of hypertensive patients should always include an assessment of renal function.

Patients should be advised to report any lightheadedness, particularly during the initial days of therapy, and to discontinue the medication if syncope occurs until they have consulted their prescribing physician. It is important for patients to avoid using potassium-containing salt substitutes without prior consultation. Female patients of childbearing age should be informed about the risks associated with Lisinopril and Hydrochlorothiazide Tablets during pregnancy and should discuss treatment options if planning to conceive. Patients must report any signs of angioedema, such as swelling of the face or difficulty breathing, and should refrain from taking further medication until they have consulted their physician. Additionally, those taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and to undergo regular skin cancer screenings.

FDA Insert (PDF)

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

View full prescribing information (PDF)