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 to off-white crystalline powder, soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol.

Hydrochlorothiazide is identified as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, with an empirical formula of C7H8ClN3O4S2 and a molecular weight of 297.72. This compound is a white or practically white crystalline powder, slightly soluble in water, and freely soluble in sodium hydroxide solution.

The tablets are formulated for oral administration and are available in three strengths: 10 mg of lisinopril and 12.5 mg of hydrochlorothiazide; 20 mg of lisinopril and 12.5 mg of hydrochlorothiazide; and 20 mg of lisinopril and 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, 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 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.

It is also noted that some antihypertensive medications may exhibit smaller 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 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 lisinopril and hydrochlorothiazide tablets may be considered. The appropriate combinations include 10 mg/12.5 mg or 20 mg/12.5 mg, selected based on the patient's 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 recommended that the hydrochlorothiazide dose not be increased until a period of 2 to 3 weeks has elapsed to assess the patient's response adequately.

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

Contraindications

Lisinopril and hydrochlorothiazide is contraindicated in patients with a known hypersensitivity to this product. It is also contraindicated in individuals with a history of angioedema associated with previous treatment using an angiotensin-converting enzyme inhibitor, as well as in patients with hereditary or idiopathic angioedema.

Additionally, due to the hydrochlorothiazide component, this medication is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Co-administration of aliskiren with lisinopril and hydrochlorothiazide is contraindicated in patients with diabetes.

Warnings and Precautions

Patients receiving angiotensin-converting enzyme (ACE) inhibitors, including lisinopril and hydrochlorothiazide, may experience a range of serious adverse reactions.

Anaphylactoid and Angioedema Reactions Anaphylactoid reactions, including angioedema affecting the face, extremities, lips, tongue, glottis, and/or larynx, have been reported in patients treated with ACE inhibitors. These reactions can occur at any time during treatment. In the event of angioedema, lisinopril and hydrochlorothiazide should be discontinued immediately, and appropriate therapy and monitoring should be initiated until complete resolution of symptoms is achieved. It is important to note that fatalities have been reported due to angioedema associated with laryngeal or tongue edema. Additionally, intestinal angioedema has been documented, with symptoms resolving upon cessation of the ACE inhibitor.

Desensitization and Membrane Exposure Risks Life-threatening anaphylactoid reactions may occur in patients undergoing desensitization treatment with hymenoptera venom while receiving ACE inhibitors. Furthermore, sudden and potentially life-threatening reactions have been observed in patients undergoing dialysis with high-flux membranes while concurrently treated with an ACE inhibitor.

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

Hematological Monitoring Patients with collagen vascular disease and renal disease should undergo periodic monitoring of white blood cell counts due to the risk of leukopenia, neutropenia, or agranulocytosis.

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

Fetal Toxicity The use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy is associated with reduced fetal renal function and increased morbidity and mortality in both the fetus and neonate.

General Precautions Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at an increased risk of developing angioedema while on treatment. Caution is advised when prescribing thiazides to patients with renal disease, as they may precipitate azotemia. Additionally, thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease.

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

Healthcare professionals are advised to remain vigilant regarding these warnings and precautions to ensure patient safety during treatment with ACE inhibitors.

Side Effects

Patients receiving treatment may experience a range of adverse reactions. The most common adverse reactions, occurring in more than 1% of participants in controlled trials, include dizziness (7.5%, with 0.8% leading to discontinuation), headache (5.2%, 0.3% discontinuation), cough (3.9%, 0.6% discontinuation), and fatigue (3.7%, 0.4% discontinuation). Other notable 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). 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) have also been reported.

Additional adverse reactions noted in clinical trials and post-marketing experiences include chest pain, abdominal pain, syncope, chest discomfort, fever, and viral infections. Cardiovascular effects such as palpitations and orthostatic hypotension have been observed. Digestive system reactions may include gastrointestinal cramps, dry mouth, constipation, and heartburn. Musculoskeletal complaints such as back pain, shoulder pain, knee pain, and myalgia have also been reported. Nervous system and psychiatric effects include decreased libido, vertigo, depression, and somnolence. Respiratory issues such as common cold, nasal congestion, influenza, bronchitis, and dyspnea have been noted, along with skin reactions like flushing, pruritus, and skin inflammation. Special senses may be affected, leading to blurred vision and tinnitus, while urogenital issues such as urinary tract infections have also been documented.

Serious adverse reactions, although rare, include anaphylactoid reactions, hepatic failure (which may progress to fulminant hepatic necrosis), and hematological disorders such as leukopenia, neutropenia, and agranulocytosis, particularly in patients with renal impairment or collagen vascular disease. Hydrochlorothiazide has been associated with acute myopia and secondary angle-closure glaucoma as an idiosyncratic reaction.

Warnings include the potential for angioedema affecting the face, extremities, lips, tongue, glottis, and/or larynx, with rare cases of intestinal angioedema reported in post-marketing experience. Hypotension has been observed in 1.4% of patients, with orthostatic hypotension occurring in 0.5% and syncope in 0.8%. Additionally, a persistent nonproductive cough has been reported with ACE inhibitors, which typically resolves upon discontinuation of therapy.

Drug Interactions

Patients receiving lisinopril and hydrochlorothiazide should be aware of potential drug interactions that may necessitate monitoring or dosage adjustments.

Lisinopril Interactions

Pharmacodynamic Interactions:

• Diuretics: Patients on diuretics, particularly those newly initiated on therapy, may experience significant hypotension upon starting lisinopril. To mitigate this risk, it is advisable to consider discontinuing the diuretic or increasing dietary salt intake prior to initiating lisinopril.

• Non-Steroidal Anti-Inflammatory Agents (NSAIDs): Co-administration of NSAIDs, including selective COX-2 inhibitors, may lead to renal function deterioration, 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 by NSAIDs.

• Dual Blockade of the Renin-Angiotensin System (RAS): The combination of lisinopril with angiotensin receptor blockers or aliskiren can increase the risk of hypotension, hyperkalemia, and renal function alterations, including acute renal failure. Close monitoring of blood pressure, renal function, and serum electrolytes is recommended.

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

Pharmacokinetic Interactions:

• Potassium-Sparing Agents: The concomitant use of lisinopril with potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium levels. Caution is advised, and serum potassium levels should be monitored.

• Lithium: The use of lisinopril with lithium has been associated with increased risk of lithium toxicity. Frequent monitoring of serum lithium levels is recommended when these agents are used together.

• Other Agents: Lisinopril can be safely co-administered with nitrates and/or digoxin without significant adverse interactions. No clinically relevant pharmacokinetic interactions have been observed with propranolol, digoxin, or hydrochlorothiazide. Food does not affect the bioavailability of lisinopril.

Hydrochlorothiazide Interactions

Pharmacodynamic Interactions:

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

• Antidiabetic Drugs: Dosage adjustments may be necessary for oral antidiabetic agents and insulin when used concurrently with hydrochlorothiazide.

• Other Antihypertensive Drugs: Hydrochlorothiazide may have an additive effect when used with other antihypertensive medications.

• Corticosteroids and ACTH: These agents may exacerbate electrolyte depletion, particularly hypokalemia.

• Pressor Amines (e.g., Norepinephrine): There may be a reduced response to pressor amines, although this does not preclude their use.

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

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

Pharmacokinetic Interactions:

• Cholestyramine and Colestipol Resins: These resins can significantly impair the absorption of hydrochlorothiazide, with cholestyramine potentially reducing absorption by up to 85% and colestipol by up to 43%.

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): The diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide may be diminished when used with NSAIDs. Close observation is warranted when these agents are co-administered with lisinopril and hydrochlorothiazide.

• 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

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 could also facilitate removal, there is currently no clinical experience to support this procedure.

The safety and effectiveness of lisinopril and hydrochlorothiazide in pediatric patients have not been established, indicating a need for caution when considering these medications in this population.

Geriatric Use

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

In general, dose selection for geriatric patients should be approached with caution. It is advisable to initiate treatment at the lower end of the dosing range, taking into account the increased likelihood of diminished hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies. Given that this medication is primarily excreted by the kidneys, the risk of adverse reactions may be heightened in patients with impaired renal function.

Therefore, careful consideration should be given to dose adjustments in elderly patients, particularly due to their propensity for decreased renal function. It is essential that the evaluation of hypertensive elderly patients includes a thorough assessment of renal function to ensure safe and effective treatment.

Pregnancy

Female patients of childbearing age should be informed about the potential consequences of exposure to lisinopril and hydrochlorothiazide during pregnancy. It is essential for healthcare providers to discuss treatment options with women who are planning to become pregnant, as the use of these medications may pose risks to fetal outcomes.

Patients are advised to report any pregnancies to their physicians as soon as possible to ensure appropriate management and consideration of alternative therapies.

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

Renal Impairment

In patients with renal impairment, thiazide-containing combination products are not recommended, particularly in those with severe renal dysfunction. Thiazides may precipitate azotemia in patients with renal disease, and cumulative effects of the drug can develop in individuals with impaired renal function.

Periodic monitoring of white blood cell counts should be considered for patients with collagen vascular disease and renal disease. While excessive hypotension is rarely observed in uncomplicated hypertensive patients, it may occur in salt/volume-depleted individuals, such as those receiving vigorous diuretic therapy or patients on dialysis.

In patients with severe congestive heart failure, whether or not associated with renal insufficiency, excessive hypotension has been noted, which may lead to oliguria, progressive azotemia, and, in rare cases, acute renal failure or death. Patients receiving ACE inhibitors, including lisinopril and hydrochlorothiazide, may experience a range of adverse reactions, some of which can be serious, especially in those with renal impairment.

Caution is advised when using hydrochlorothiazide in patients with severe renal disease. Additionally, anaphylactoid reactions have been reported in some patients undergoing dialysis with high-flux membranes while concurrently treated with an ACE inhibitor. Patients with a history of angioedema unrelated to ACE-inhibitor therapy may also be at an increased risk of angioedema when receiving an ACE inhibitor.

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, specific treatment information is limited. Management of such incidents is primarily symptomatic and supportive.

It is recommended that therapy with lisinopril and hydrochlorothiazide be discontinued immediately, and the patient should be monitored closely for any adverse effects. Suggested interventions may include the induction of emesis and/or gastric lavage to mitigate absorption of the drug. Additionally, it is crucial to address any dehydration, electrolyte imbalances, and hypotension through established medical procedures.

The most common manifestation of overdosage is hypotension. In such instances, the standard treatment involves the intravenous infusion of normal saline solution to restore blood pressure.

Animal studies have indicated that following a single oral dose of 20 mg/kg, no lethality was observed in rats; however, one out of twenty mice did succumb to the same dosage.

For patients undergoing hemodialysis, it is important to note that lisinopril can be effectively removed from the system through this procedure.

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 with this combination. However, in rats, decreased maternal weight gain and reduced fetal weight were observed at doses as low as 3/10 mg/kg/day, the lowest tested. This reduction in fetal weight was associated with a delay in fetal ossification, which was not present in saline-supplemented animals receiving the same combination of doses.

The use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with reduced fetal renal function, leading to increased morbidity and mortality in both fetal and neonatal populations. Oligohydramnios resulting from such drug use can contribute to fetal lung hypoplasia and skeletal deformities. Potential adverse effects in neonates may include skull hypoplasia, anuria, hypotension, renal failure, and death. Non-teratogenic effects may encompass fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions observed in adults.

Lisinopril, in combination with hydrochlorothiazide, was not found to be mutagenic in microbial mutagen tests using Salmonella typhimurium or Escherichia coli, with or without metabolic activation, nor in a forward mutation assay using Chinese hamster lung cells. Additionally, no DNA single strand breaks were produced in an in vitro alkaline elution assay using rat hepatocytes, and no increases in chromosomal aberrations were observed in both in vitro tests with Chinese hamster ovary cells and in vivo studies in mouse bone marrow.

Long-term studies demonstrated no evidence of tumorigenicity when lisinopril was administered to male and female rats for 105 weeks 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 carcinogenicity was observed in male and female mice administered lisinopril for 92 weeks at doses up to 135 mg/kg/day (about 84 times the maximum recommended daily human dose).

Hydrochlorothiazide was also shown to be non-genotoxic in vitro in the Ames mutagenicity assay and in the Chinese Hamster Ovary test for chromosomal aberrations, as well as in vivo in assays involving mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive results were only noted in the in vitro CHO Sister Chromatid Exchange and Mouse Lymphoma Cell assays.

In terms of fertility, hydrochlorothiazide did not adversely affect the reproductive capabilities of mice and rats of either sex when administered doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to conception and throughout gestation.

Studies in rats indicate that lisinopril has poor penetration across the blood-brain barrier and does not accumulate in tissues following multiple doses. However, radioactivity was detected in the milk of lactating rats after administration of labeled lisinopril. Whole body autoradiography revealed radioactivity in the placenta of pregnant rats, but none was found in the fetuses. Hydrochlorothiazide was shown to cross the placenta but not the blood-brain barrier.

Postmarketing Experience

Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx has been reported in patients treated with angiotensin converting enzyme (ACE) inhibitors, including lisinopril. This adverse event may occur at any time during treatment. Notably, ACE inhibitors have been associated with a higher incidence of angioedema in black patients compared to nonblack patients.

Intestinal angioedema has also been documented in patients receiving ACE inhibitors. These patients typically presented with abdominal pain, which may have been accompanied by nausea or vomiting. In some instances, there was no prior history of facial angioedema, and C-1 esterase levels were found to be normal. Diagnosis of intestinal angioedema was made through abdominal CT scans, ultrasounds, or surgical procedures, with symptoms resolving upon discontinuation of the ACE inhibitor.

Postmarketing experience has revealed rare cases of leukopenia/neutropenia and bone marrow depression, although a causal relationship to lisinopril cannot be definitively established. It is advisable to consider periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease.

Rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice or hepatitis and may progress to fulminant hepatic necrosis, and in some cases, death. The underlying mechanism of this syndrome remains unclear. Patients receiving ACE inhibitors who develop jaundice or significant elevations in hepatic enzymes should discontinue the medication and receive appropriate medical follow-up.

In clinical trials, adverse effects related to hypotension were observed, with hypotension occurring in 1.4% of patients, orthostatic hypotension in 0.5%, and other orthostatic effects in 3.2%. Additionally, syncope was reported in 0.8% of patients.

Overall, rare cases of intestinal angioedema have been noted in the postmarketing experience.

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 a decrease in 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, as this may have implications for their treatment.

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. Healthcare providers should discuss treatment options with women who are planning to become pregnant, and patients should be encouraged to report any pregnancies to their physicians as soon as possible.

Storage and Handling

The product is supplied in accordance with the following specifications: it should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. It is essential to protect the product from excessive light and humidity to maintain its integrity and efficacy.

Additional Clinical Information

Periodic monitoring of serum electrolytes is recommended to identify potential imbalances, particularly in patients experiencing excessive vomiting or receiving parenteral fluids. In clinical studies, minor reversible increases in blood urea nitrogen and serum creatinine were noted in patients with essential hypertension treated with lisinopril and hydrochlorothiazide. Additionally, small decreases in hemoglobin and hematocrit were frequently observed, though these were rarely clinically significant unless accompanied by other causes of anemia. Rare instances of elevated liver enzymes and/or serum bilirubin have also been documented.

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

FDA Insert (PDF)

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

View full prescribing information (PDF)